The diagnostic term thyroiditis includes a group of inflammatory or inflammatory-like conditions. The terminology that has been employed is confusing, and no classification is ideal. We prefer the following nomenclature, which takes into account the cause when known.
- Infectious thyroiditis , also referred to as either acute or chronic, and which in fact may be either, along with the qualifying term suppurative (AST), nonsuppurative, or septic thyroiditis. It includes all forms of infection, other than viral, and is caused by invasion of the thyroid by bacteria, mycobacteria, fungi, protozoa, or flatworms. The disorder is rare.
- DeQuervain’s thyroiditis, commonly known as subacute thyroiditis (SAT ) but also termed subacute nonsuppurative thyroiditis, granulomatous, pseudotuberculous, pseudo-giant cell or giant cell thyroiditis, migratory or creeping thyroiditis, and struma granulomatosa. This condition, most likely of viral origin, lasts for a week to a few months, with a tendency to recur. The eponym was selected because of its uncertain cause.
- Autoimmune thyroiditis , commonly referred to as chronic, Hashimoto’s, or lymphocytic thyroiditis and also known as lymphadenoid goiter and struma lymphomatosa. This indolent disease usually persists for years and in the Western world is the principal cause of non-iatrogenic primary hypothyroidism. Nonspecific focal thyroiditis, characterized by local lymphoid cell infiltration without parenchymal changes, may be a variant of the autoimmune disease. The condition is covered in detail in Chapter 8. Another form of thyroiditis, also believed to be of autoimmune cause, has recently been described. It has been variably referred to as painless, silent, occult, subacute, subacute nonsuppurative, and atypical (silent) subacute thyroiditis, as well as hyperthyroiditis, transient thyrotoxicosis with low thyroidal RAIU and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism. There is no agreement on an inclusive name. The features of this disease entity overlap deQuervain’s thyroiditis and Hashimoto’s thyroiditis. The clinical course, with the exception of a very high erythrocyte sedimentation rate and pain in the thyroid are indistinguishable from deQuervain’s thyroiditis. Yet, histologically, the condition cannot be differentiated from a milder form of Hashimoto’s disease. This condition often occurs in the postpartum period and is also termed postpartum thyroiditis. All forms of autoimmune thyroiditis are considered in Chapter 8.
- Riedel’s thyroiditis , another disorder of unknown etiology. Synonyms include Riedel’s struma, ligneous thyroiditis and invasive fibrous or chronic sclerosing thyroiditis. This condition is characterized by overgrowth of connective tissue which often extends into neighboring structures.
- Miscellaneous varieties of thyroid inflammation or infiltration including local manifestations of a generalized disease processes. Among these are sarcoid and amyloid involvement of the thyroid. Radiation and direct trauma to the thyroid gland may also cause thyroiditis.
The thyroid gland is remarkably resistant to infection. This has been attributed to its high vascularity, lymphatic drainage, the presence of large amounts of iodine in the tissue, the fact that hydrogen peroxide is generated within the gland as a requirement for the synthesis of thyroid hormone and its normal encapsulated position away from external structures. However, in certain situations, particularly in children(1-4), a persistent fistula from the pyriform sinus may make the left lobe of the thyroid particularly susceptible to abscess formation (5) , (6) , (4) , (7-10). Acute suppurative thyroiditis (AST) is a rare condition, reported to account for 0.1-0.7% of thyroid disease(11) which may result in up to 12% or higher mortality if left untreated(12) , (11) , (13). Recurrent left-sided thyroid abscess has also been reported due to a fourth branchial arch sinus fistula (14). A review of 526 cases of congenital fourth branchial arch anomalies (15) noted that they presented with acute suppurative thyroiditis in 45% of cases. Acute thyroiditis from a periapical abscess of an inferior molar has been reported (16). In the immuno-compromised host, fungal infection may occur (17-20). Occasionally, acute bacterial suppurative thyroiditis occurs in children receiving cancer chemotherapy (21). Rarely, infection will occur in a cystic or degenerated nodule. As will be discussed, the principal differential diagnosis is generally between acute (AST), meaning infectious, and subacute (SAT), meaning post-viral (non-infectious) inflammation of the gland.
Virtually any bacterium can infect the thyroid (Table 1). Streptococcus, staphylococcus, pneumococcus, salmonella, klebsiella (22-26), bacteroides, t. pallidum, pasteurella spp (27), multocida (28), porphyromonas(29), eikenella (30-32) and m. tuberculosis (33-36) have all been described. The subject has been extensively reviewed (17) , (37) , (38). In addition, certain fungi, including coccidioides immitis, aspergillus, actinomycosis, blastomycosis (39-42), candida albicans, nocardia (43-45), actinobacter baumanii (13) cryptococcus (46) and pneumocystis (47) have also been associated with thyroiditis. In the latter cases, the hosts have often been immuno-compromised, either due to malignancy or to AIDS (48) , (49). Rarely acute suppurative thyroiditis is due to thyroid abscess with deep neck infection(50). Malignancy may also be associated with thyroid abscess due to a fistulous connection (51), a thyroid abscess due to clostridium perfringens has been reported (52) and clostridium septicum is almost always associated with carcinoma of the colon (53). Metastatic breast cancer has been described as presenting clinically with acute thyroiditis (54). Recently, the role of diagnostic fine needle thyroid aspiration has been emphasized, firstly as a factor in the cause of acute suppurative thyroiditis with associated thyrotoxicosis in a patient with atopic dermatitis (55), also being causative in a case of secondary infection after aspirating a simple cyst (52), associated with necrosis in a patient with papillary thyroid carcinoma (56) and an intra-thyroidal abscess in a multinodular goiter which grew E. coli (57). Care should be taken when performing FNAC in patients who may be susceptible to tracking of infection into the thyroid.
Most commonly, however, especially in children, infection of the thyroid gland is a result of direct extension from an internal fistula from the pyriform sinus (4) , (58) , (7) , (9) , (59) , (38) , (60). This tract is thought to represent the course of migration of the ultimo branchial body from the site of its embryonic origin in the fifth pharyngeal pouch (8). Careful histopathological studies of these fistulae have demonstrated that they are lined by squamous columnar or ciliated epithelium and occasionally form branches in the thyroid lobe (4) , (9). In addition, occasional cells positive for calcitonin have been found in the fistulae and increased numbers of C-cells were noted in the thyroid lobe at the point of termination of the tract. The predominance of acute thyroiditis in the left lobe of the thyroid gland, particularly in infants and children, is explained by the fact that the right ultimo branchial body is often atrophic and does not develop in the human (as well as in other species such as reptiles). The reason for this phenomenon is not known. Acute thyroiditis may involve a normal gland, arise in a multinodular goiter (61) or even Hashimoto’s thyroiditis . At times, no source of infection can be demonstrated. The possibility of a persistent thyroglossal duct should be considered for patients with midline infections (62). Acute thyroiditis has arisen as the initial presentation of juvenile systemic lupus erythematosus (63) and has also occurred due to septic emboli derived from infective endocarditis(64) , (65).
Pathology Pathological examination reveals characteristic changes of acute inflammation. With bacterial infections, heavy polymorphonuclear and lymphocytic cellular infiltrate is found in the initial phase, often with necrosis and abscess formation. Fibrosis is prominent as healing occurs. In material obtained by fine needle aspiration, the infectious agent may be seen on a gram, acid fast or appropriate fungal stains (7) and grown out in culture for antibiotic sensitivity assessment.
Although acute thyroiditis is quite rare (about 2 patients per year in a large tertiary care hospital), cases of suppurative thyroiditis are increasing due to the higher incidence of immune-compromised patients. It has been estimated to be much more common in the pediatric age group because of its relationship with pyriform sinus fistulae, where 90% of lesions develop in the left lobe of the thyroid (65) although it is still quite unusual. It has been estimated that about 8% of cases occur in adulthood (66-68) , (65) , (69-72). The dominant clinical symptom is pain in the region of the thyroid gland which may subsequently enlarge and become palpably hot and tender. The patient is unable to extend the neck and often sits with the neck flexed in order to avoid pressure on the thyroid gland. Swallowing is painful. There are usually signs of infection in structures adjacent to the thyroid, local lymphadenopathy as well as temperature elevation and, if bacteremia occurs, chills. Gas formation with suppurative thyroiditis has been noted (73-76). Symptoms are generally more obvious in children than in adults. Adults may present with a vague slightly painful mass in the thyroid region without fever, which may raise the possibility of a malignancy. Suppurative thyroiditis may even spread to the chest producing necrotizing mediastinitis and pericarditis in the absence of a pyriform sinus fistula (77) , (50) , (78) , (79). It may occur more commonly in the fall and winter following upper respiratory tract infections.
In general, there are no signs or symptoms of hyper- or hypothyroidism. However, exceptions to both have been reported particularly if the thyroiditis is generalized, such as occurs with fungal processes (46) or mycobacterial infections. At times, even in patients with bacterial thyroiditis, destruction of the thyroid gland is sufficient to release thyroid hormone in amounts sufficient to cause symptomatic thyrotoxicosis (28) , (34). The adult thyroid gland contains approximately 600 ug of T4/g (80). Given a typical 15 to 20 g gland, sufficient hormone can be released to cause transient thyrotoxicosis. Associated thyrotoxicosis has also been reported in children and adults (5) , (28) , (55) , (81), in one series, 12% presented with thyrotoxicosis and 17% were said to be hypothyroid(13). This variety of thyroid function findings clearly increases the difficulty of differentiating AST from subacute thyroiditis (SAT) as both present with thyroidal pain. Unique presentations of AST have been reported where initial thyrotoxicosis has been followed by hypothyroidism and spontaneous normalization of thyroid function after treatment of the AST(29).
Pain in the anterior neck will usually lead to a consideration of the possibility of thyroiditis. Since the major differential diagnosis will lie between acute suppurative thyroiditis and subacute thyroiditis, it is critical to compare the history, physical, and particularly laboratory data in these two conditions (see Table 3). In general, the patient with acute thyroiditis appears septic, has greater and more localized pain in the thyroid gland, may have an associated upper respiratory infection, has lymphadenopathy and may be immuno-compromised. Localization of the tenderness to the left lobe should suggest the possibility of an infection as should any erythema or apparent abscess formation. The presence of an elevated white blood count with a shift to the left would argue for infection, however, elevations in sedimentation rate are common in both acute and subacute thyroiditis. As mentioned, patients with bacterial thyroiditis are
|Table 1 Microbiology of Acute Suppurative Thyroiditis|
|Aerobic Staphylococcus aureus Streptococcus pyogenes Streptococcus epidermidis Streptococcus pneumoniae|
|Anaerobic Clostridium septicum(53) Gram negative bacilli Peptostreptococcus spp.|
|Bacterial Atypical mycobacteria Clostidium perfringens(52) Eikenella corrodens Enterobacteriaceae Haemophilus influenzae Klebsiella spp. Mycobacterium tuberculosis Porphyromonas(29) Salmonella spp. Streptococcus viridans Treponema pallidum Echinococcus spp|
|Fungal Aspergillus spp Blastomycosis Candida spp. Coccidioides immitis Pneumocystis jiroveci|
usually euthyroid but a thyrotoxic presentation has been noted in 8-12%(82) , (13) and hypothyroidism was noted in 17% of one series(82). Thyrotoxicosis is clearly more common, 52% at 7 days and 65% by 30 days of neck pain in patients with subacute thyroiditis (83). The thyrotoxic presentation therefore makes for a difficult differential diagnostic problem to separate AST from SAT which may have significant impact in the selection of initial therapy.
Depending on the age and clinical circumstances, one may wish to proceed with invasive or non-invasive studies. Discriminating tests for recognizing a difference between AST and SAT have been considered a radio-nuclide uptake or scan usually showing a very low value in subacute thyroiditis with a normal value found in the patient with very localized mild bacterial thyroiditis (38). More frequently however both conditions are associated with a low 123-I uptake at initial presentation(84) limiting the power of nuclear scanning to effectively differentiated these two conditions.
A thyroid ultrasound may be done but characteristic findings vary depending on the phase of AST during which the patient is observed. In the early inflammatory phase of AST, when obvious abscess formation is not evident, the ultrasound may show a localized hypoechoic process with an obscure border and effacement between the thyroid and surrounding perithyroidal tissues(85). During the acute inflammatory stage of AST, clear cut abscess formation is noted in the affected thyroidal tissue(85). Alternatively, the application of sonoelastography may reveal very stiff lesions corresponding to the areas of the thyroid which are especially painful(86) during acute phases of the AST episode which soften significantly as the patient responds to treatment(86). As the AST resolves with appropriate treatment, ultrasound images may demonstrate deformity of the gland characterized by atrophy of the affected lobe, air pockets in the thyroidal tissue and scarring of the perithyroidal tissues(85).
A CT scan may be useful in identifying the location of the abscess, but this has been said to be required only in unusual situations (87). The CT findings also vary with the stage of AST. In the early inflammatory stage, nonspecific low density areas in the swollen thyroid along with potential tracheal displacement may be seen(85). In the acute inflammatory stage, a CT can also demonstrate edema of the ipsilateral hypopharynx, and abscess formation. In the late inflammatory stage, deformity of the thyroid, atrophy of the affected lobe and scarring of the perithyroidal tissues may be observed(85). Recent reviews indicate a significant role for CT in the initial evaluation of those with AST(85) , (11). As outlined above, during the earliest stages of AST both CT and ultrasound findings may fail to effectively differentiate between AST and SAT. In this circumstance the use of a fine needle aspiration (FNA) has been demonstrated to be very useful as outlined below. Gallium scans are sometimes performed in the course of an evaluation for a fever of unknown origin. Localization of gallium to the thyroid gland would be a very useful finding confirming thyroid inflammation as the source of the problem but the differential of gallium positive thyroid tissue will also include the presence of Riedel’s thyroiditis(88).
If an infectious process is identified, particularly of the left lobe of a younger individual, then a barium swallow should be performed with attention to the possibility of a fistulous tract located on the left side between the pyriform sinus and the thyroid gland. The barium swallow has very good sensitivity in detecting the presence of the fistular tracts as 89-97% of those examined in early and acute stages of AST were confirmed with this technique(85). Other methods of documenting the presence of a fistula are also utilized. On follow up ultrasound an ‘emerging echogenic tract sign’ suggests an associated pyriform sinus thyroid fistula (89). During a CT scan procedure the patient can be asked to blow into a syringe, the so called “trumpet maneuver”, which may help to identify a piriform sinus fistula (90), a recent series suggests that timing may influence the ability of this maneuver to demonstrate the presence of the fistula as only 20% of those examined in the acute inflammatory phase revealed a fistula while 54% of those evaluated in the late inflammatory phase had a fistula documented(85) with the “trumpet maneuver”. A ‘light guided procedure’ to visualize the tract may also help (91). Transnasal flexible fiberoptic laryngoscopy has become increasingly utilized to identify the presence of the fistular tract(11). This approach has been estimated to have similar sensitivity of documenting the tracts as barium swallow and CT methods(92-94) and can also be utilized for the instillation of chemocauterizing agents at an appropriate time after the resolution of the acute infection(95) , (92) , (82) , (93).
Occasionally, pain from an infectious process elsewhere in the neck will present as anterior neck tenderness. For example, a retropharyngeal abscess may present with typical symptoms of acute thyroiditis. The thyroid gland, however, will have a normal uptake, be normal on scan, and only on CT scan will the retropharyngeal abscess be recognized. The tendency for the pain of thyroid inflammation to be referred to the throat or ears should be kept in mind, although recognition of the anatomic source of the problem is usually not such a difficult issue in patients with acute thyroiditis due to their localized symptoms. While patients with tuberculosis or parasitic infections tend to have a more indolent course, these infections can present with acute symptoms and this possibility should be considered if the epidemiology is consistent. For example, thyroidal echinococcosis occurs in countries in which this parasite is endemic (96). Trypanosomiasis of the thyroid has also been reported (38).
A fine needle aspiration (FNA) performed in either of the acute phases of AST is important as the FNA has a superior ability to differentiate the patient with AST from those with subacute thyroiditis by cytologic criteria and also provides appropriate bacteriologic specificity allowing more accurate antibiotic selection(11) for the patient documented to have AST. In addition, transcutaneous aspiration of the infectious material can be performed to relieve pressure on a displaced trachea in patients with a compromised airway(11). Finally FNA may be seen as the most accurate means of differential diagnosis(97) when a thyrotoxic presentation is encountered. Establishing a firm diagnosis of AST allows appropriate antibiotic therapy to be prescribed when a trial of glucocorticoids for empirically assumed SAT might result in both delay in diagnosis as well as initiation of a potentially wrong therapy(29).
A recent clinical review (11) concluded that there may be a trend toward less invasive management during active inflammation and infection. Despite lack of randomized controlled trials algorithms for acute and long term management were suggested by these authors. Miyauchi (84), who has a very large experience of the condition, has cautioned that consideration of the basic anomaly predisposing the patient to thyroid gland infection must be duly considered. The diagnosis and choice of antibiotic therapy are often aided by microscopic examination and appropriate staining of a fine needle aspirate. The procedure is best done under ultrasound guidance so that the source of the specimen is identified. It may also serve as a mechanism for drainage of an abscess and can be repeated to facilitate healing. Some abscesses will require surgical exploration and drainage. The choice of therapy will also depend on the immune status of the patient. Systemic antibiotics are required for severe infections. Candida albicans thyroiditis can be treated with amphotericin B and 5 fluconazole 100 mg daily. The proper treatment of an acute thyroiditis in children generally requires the surgical removal of the fistula (4) , (7) , (9), although surgical treatment should be delayed until the inflammatory process is resolved (98) , (99).Combining this with partial thyroidectomy may further decrease the recurrence rate (15). Alternatively, fistula tract ablation can be achieved either by surgical resection which has been associated with recurrence free survival (85), or less invasively obliterated with the instillation of a chemocauterizing agent which has also been demonstrated to result is satisfactory outcomes (95) , (92) , (85) , (93).
The disease may occasionally prove fatal(79). In some patients with thyroiditis, the destruction may be sufficiently severe that permanent hypothyroidism results (61). Thus, patients with a particularly diffuse thyroiditis should have follow-up thyroid function studies performed to determine that this has not occurred. Surgical removal of a fistula or branchial pouch sinus (98) , (99) is required to prevent recurrence.
Subacute thyroiditis (SAT) sometimes referred to as granulomatous or De Quervain’s thyroiditis is a spontaneously remitting inflammatory condition of the thyroid gland that may last for weeks to several months (100) , (38) , (101). It has a tendency to recur. The gland is typically involved as a whole, and thyroidal RAIU is much depressed. Transient hyperthyroxinemia, elevation of the serum thyroglobulin concentration and the erythrocyte sedimentation rate and sometimes the WBC during the early acute phase are characteristic if not pathognomic.
A cause can rarely be established. A tendency for the disease to follow upper respiratory tract infections or sore throats has suggested a viral infection. Earlier suggestions that the disease may represent a bacterial infection have been disproven. An autoimmune reaction is also unlikely. The development during the illness of cell-mediated immunity against various thyroid cell particulate fractions or crude antigens appears to be related to the release of these materials during tissue destruction(102) , (103).
Although the search for a viral cause has usually been unrewarding, a few cases seem to be due to the virus that causes mumps(104) , (101). The disease has occurred in epidemic form. High titers of mumps antibodies have been found in some patients with subacute thyroiditis, and occasionally parotitis or orchitis is associated with thyroiditis. The mumps virus has been cultured directly from thyroid tissue involved by subacute thyroiditis. Although the mumps virus seems to be one discrete etiologic factor, the disease has been reported in association with other viral conditions including measles, influenza, H1N1 influenza(105), adenovirus infection, infectious mononucleosis(106), myocarditis, cat scratch fever, and coxsackie virus (Figure 1) (107), most recently SAT has been reported following hand-foot-mouth disease due to coxsackie B4(108). Two comprehensive studies (109) , (110) failed to find evidence of enteroviruses in 27 patients and Epstein-Barr virus or cytomegalo virus in 10 patients, respectively but a single case report has implicated EB virus in a case of subacute thyroiditis with typical clinical features (111) and cytomegalo virus has now been reported in an infant (112).Numerous attempts to culture viruses from cases not associated with mumps have failed. Virus-like particles have been demonstrated in the follicular epithelium of a single patient suffering from subacute thyroiditis (107). However, viral antibody titers to common respiratory tract viruses are often elevated in these patients. Since the titers fall promptly, and multiple viral antibodies may appear in the same patient, the elevation probably is an anamnestic response to the inflammatory condition. (Figure 1, above) As stated in a recent review (114) it seems that the thyroid could respond with thyroiditis after invasion by a variety of different viruses but no single agent is likely to be causative.
Histo-compatibility studies show that 72% of patients with subacute thyroiditis manifest HLA-Bw35 (115). Familial occurrence of subacute thyroiditis associated with HLA-B35 has been reported (116-119). Thus, the susceptibility to subacute thyroiditis is genetically influenced and it has also been suggested that subacute thyroiditis might occur by transmission of viral infection in genetically predisposed individuals (112). A reported association between subacute thyroiditis and acute febrile neutrophilic dermatosis (Sweet’s syndrome) (120) , (121) may imply a common role for cytokines in both these conditions.
New treatments, particularly those in which there is manipulation of the immune system, have led to the development of subacute thyroiditis (122). Infusion of interleukin 2 caused hyperthyroxinemia with a low radioiodine uptake in six patients who received this in combination with tumor necrosis factor (TNF) α or γ interferon (123). The patients proceeded to pass through the pattern of hyperthyroidism and transient hypothyroidism, with a re-establishment of normal thyroid function typical of the patient with autoimmune painless thyroiditis. However, none of the patients had detectable antithyroid antibodies. This condition is thus intermediate between subacute lymphocytic (painless) thyroiditis (Chapter 13) and subacute thyroiditis which is typically painful. Patients have developed subacute thyroiditis after influenza vaccination (124) , (125) suggesting immune alteration as a contributory factor. In patients with chronic hepatitis C studies following interferon therapy (IFN) showed that a minority (15%) developed a destructive thyroiditis while others had a mild elevation of TSH (123). IFN can exacerbate previous thyroid autoimmunity and cause destructive thyroidal changes de novo. Subacute thyroiditis has also been noted in patients treated with combination therapy of IFN plus ribavirin for this disease (126) , (127), as well as during treatment of hepatitis B with Interferon (128). Peginterferon alpha-2a has also been reported to cause subacute thyroiditis (129) and the condition is seen in Takayasu’s arteritis suggesting an immune abnormality (130). On the other hand, subacute thyroiditis has been reported in patients receiving long term immunosuppressive therapy suggesting a minimal role for autoimmunity in the condition (131) , (132). Other reports of subacute thyroiditis for example with renal cell carcinoma (133), following the administration of cardiac catheterization dye(134), after gastric bypass (135) or after ginger ingestion (136) do not clearly contribute to an enhanced understanding of its etiology.
The thyroid gland may be adherent to its capsule or to the strap muscles but it can usually be dissected free, a feature distinguishing subacute thyroiditis from Riedel’s thyroiditis. The involved tissue appears yellowish or white and is more firm than normal. The gland is enlarged, and the enlargement is usually bilateral and uniform, but it may be asymmetrical, with predominant involvement of one lobe. Although the lesion may extend to the capsular surface, it can also be confined to the thyroid parenchyma and merely be palpable as a suspiciously hard area.
The macroscopic pathologic picture of subacute thyroiditis frequently bears a striking resemblance to cancer. The lesion is firm to dense in consistency, pale white in color, and has poorly defined margins that encroach irregularly on the adjacent normal thyroid. Microscopically, one sees a mixture of subacute, chronic, and granulomatous inflammatory changes associated with zones of parenchymal destruction and scar tissue. Early infiltration with polymorphonuclear leukocytes is replaced by lymphocytes and macrophages. The normal follicles may be largely replaced by an inflammatory reaction, but a few small follicles containing colloid remain (Fig. 2, below). Three dimensional cytomorphological analysis of fine needle aspiration biopsy samples from patients with subacute thyroiditis examined with scanning and transmission electron microscopy has shown a loss of a uniform, honeycomb cellular arrangement; variation in size and decrease or shortening of microvilli in follicular cells together with the appearance of round or ovoid giant cells (137). The most distinctive feature is the granuloma, consisting of giant cells clustered about foci of degenerating thyroid follicles (Fig. 2). The early literature contains accounts of tuberculous thyroiditis, a diagnosis largely based on the granulomatous tissue reaction, from which the descriptive but unfortunate term pseudotuberculous thyroiditis arose (138). Data on the mechanism of inflammation and the pathogenesis of subacute thyroiditis at the cellular level are sparse. However, a study of apoptosis and expression of Bcl 1-2 family proteins in 11 patients with SAT suggests that apoptotic mechanisms may be involved in the development of SAT (139). Growth factor rich monocytes/macrophages (containing VEGF, beta FGF, PDGF and TGF beta 1) are involved in the granulomatous stage (140). EGF is important in the regenerative stage as it has mitogenic effects on the thyrocyte. VEGF and beta FGF contribute to the angiogenesis at both these stages of the disease. Factors influencing the severity of the acute phase response during the course of SAT include serum interleukin -1 receptor antagonist which may have a significant anti-inflammatory role (141); also, a decrease in TNF alpha results in earlier resolution of experimentally induced granulomatous thyroiditis (142). The role of TNF- related apoptosis-inducing ligand (TRAIL) in promoting resolution of this condition is also being investigated (143).
Mast cells play an important part in the repair process of thyroid tissue affected by the disease via production of growth factors and biomolecules which modulate thyroid folliculogenesis and angiogenesis (144).
Subacute thyroiditis is encountered infrequently, but each year a handful of cases will be identified in a busy thyroid clinic. Woolner et al (138) collected 162 cases diagnosed on clinical grounds at the Mayo Clinic over a 5-year period; during the same time, 1,250 patients with Graves’ disease were seen. Thus, the disease had approximately one-eighth the incidence of Graves’ disease in this clinic population. During an evaluation of subtypes of hypothyroidism over a 4 year period in Denmark an incidence of subacute thyroiditis of 1.8% was found in a cohort of 685 patients with hypothyroidism (145) , (100). Although the disease has been described at all ages, it is rare in children (100) , (146). Female patients have outnumbered male patients in a ratio of 1.9-6:1, with a preponderance of cases in the third to fifth decades (147) , (148) , (37) , (101) , (138) and it has been noted as a rare cause of hyperthyroidism in pregnancy (149) , (150). In 160 patients studied during 37 years at the Mayo Clinic an age and sex adjusted incidence of 4.9 cases/100,000/year was noted (147).
Characteristically, the patient has severe pain and extreme tenderness in the thyroid region. A small minority of patients have been noted to present with painless or minimally painful subacute thyroiditis following viral symptomatology (151). These may be regarded as atypical subacute thyroiditis patients but their natural history of the disease is not known. Subacute thyroiditis has been reported to have occurred during the first trimester of pregnancy(149). When the symptom is difficulty in swallowing, the disorder may be initially mistaken for pharyngitis. Transient vocal cord paresis may occur (152). At times, the pain begins in one pole and then spreads rapidly to involve the rest of the gland (“creeping thyroiditis”). Pain may radiate to the jaw or the ears. Malaise, fatigue, myalgia and arthralgia are common. A mild to moderate fever is expected, and at times a high, swinging fever with temperatures above 104°F (40.0°C). The disease may reach its peak within 3 to 4 days and subside and disappear within a week, but more typically, a gradual onset extends over 1 to 2 weeks and continues with a fluctuating intensity for 3 to 6 weeks. Several recurrences of diminishing intensity extending over many months may be the unhappy fate of the patient.
The thyroid gland is typically enlarged two or three times the normal size or larger and is tender to palpation, sometimes exquisitely so. It is smooth and firm. Occasionally the condition may be confined to one lobe (153) , (154). Approximately one-half of the patients present during the first weeks of the illness, with symptoms of thyrotoxicosis, including nervousness, heat intolerance, palpitations, – even ventricular tachycardia (155), tremulousness, and increased sweating. These symptoms are caused by excessive release of preformed thyroid hormone from the thyroid gland during the acute phase of the inflammatory process. At least 2 cases of thyroid storm due to subacute thyroiditis have been described (156) , (157) and adverse cardiac outcomes have been reported even in individuals without preexisting cardiac history or lesions(158). As the disease process subsides, transient hypothyroidism occurs in about one-quarter of the patients. Ultimately thyroid function returns to normal and permanent hypothyroidism occurs in less than 10 percent of the cases (37) , (38) , (101). Occasionally the condition may be painless and present as fever of unknown origin (159) or associated with other findings and mimicking conditions such as temporal arteritis(160). Some clinical and laboratory features recorded in 2 recent series of SAT are shown in Table 2 (161) , (83). Liver function test abnormalities are found in half the patients and return to normal in a few months (162).
|TABLE 2 Clinical Features of Subacute Thyroiditis|
|Temp >38 0||28%||–|
|Labs-peak levels||1 week||–|
|Disease duration (days)||–||77|
|ATA: Antithyroid antibodies. US: Thyroid ultrasound. –: no dataData derived from refs (161) , (83).|
Table 3 provides a comparison between the clinical and laboratory findings of patients with subacute and acute thyroiditis (163-167) , (38) , (168). Laboratory examination may disclose a moderate leukocytosis. A curious and striking elevation of the erythrocyte sedimentation rate, at times above 100 mm/hr, or an elevated level of serum C-reactive protein (169) is a useful diagnostic clue. Recently the identification of CRP in salivary samples provides a convenient source for documenting the presence of abnormal levels in those with SAT(170). Short of a tissue diagnosis, most helpful is the characteristic combination of elevated erythrocyte sedimentation rate, high serum T4, T3, and TG concentrations in the presence of low thyroidal RAIU, TSH, and an absent or low titer of circulating TPO and TG antibodies. While the estimation of thyrotropin receptor antibodies (TRAb) in a thyrotoxic patient may be clinically useful in identifying Graves’ disease there have been reports of positive TRAb in patients with subacute thyroiditis although the frequency of this finding is low (171-174). Mild anemia and hyperglobulinemia may be present.
The value of a 99m-Tc-pertechnetate scintigraphy as a marker of disease activity and severity has been described (175). Pertechnetate scanning, although inexpensive and convenient, typically reveals little to no uptake and thus no visualization of the SAT process(175) , (176), a finding consistently reported in the literature(177) , (105) , (108) , (178) , (158) , (179). Further imaging studies have shown diffuse increased uptake of Tc-99m sestamibi(176) and Tc-99m tetrofosmin(175) in the thyroid region of patients in the acute phase (thyrotoxic) of subacute thyroiditis suggesting an ability of both agents to detect the inflammatory process associated with the disease (175) , (176). In the same patients color Doppler ultrasonography showed an absence of vascularization in the acute phase and its use in the differential diagnosis of unclear cases has been emphasized (180) , (181). Standard ultrasonigraphic images are characterized by hypoechoic appearance of the affected tissue the volume of which correlates with the severity of clinical discomfort(182). The application of newer technologies such as sonoelastography has the capacity to demonstrate markedly decreased elasticity (enhanced stiffness) in SAT lesions(86). Subacute thyroiditis may obscure the coexistence of papillary carcinoma in cases presenting with ultrasonographically diffuse hypoechoic areas (183). Subacute thyroiditis with thyrotoxicosis may also be distinguished from Graves’ hyperthyroidism by using T1- and T2- diffusion weighted magnetic resonance imaging (184) and as an intense area of uptake on (18) F-FDG PET/CT(179) , (185) although these investigation may not be available or even desirable in all centers. Fine needle aspiration biopsy is often diagnostic although patients are often alarmed at the prospect of this test due to the pain in the thyroid. However FNA may be helpful in ruling out malignancy (186) and the infection associated with localized, painful lesions of AST (see above).
Table 3. Features Useful in Differentiating Acute Suppurative Thyroiditis and Subacute Thyroiditis
|Characteristic||Acute Thyroiditis||Subacute Thyroiditis|
|History||Preceding upper respiratory infection||88%||17%|
|Symptoms of thyrotoxicosis||Uncommon||47%|
|Physical Examination of the thyroid||Painful thyroid swelling||100%||77%|
|Left side affected||85+%||not specific|
|Migrating thyroid tenderness||Possible||27%|
|Erythema of overlying skin||83%||not usually|
|Laboratory||Elevated white blood cell count||57%||25-50%|
|Erythrocyte sedimentation rate (>30mm/hr)||100%||85%|
|Abnormal thyroid hormone levels(elevated or depressed)||5-10%||60%|
|Alkaline phosphatase, transaminases increased||Rare||common|
|Needle Aspiration||Purulent, bacteria or fungi present||~100%||0|
|Lymphocytes, macrophages, some polys, giant cells||0||~100%|
|Radiological||123 I uptake low||Common||~100%|
|Abnormal thyroid scan||92%||Non-visualized|
|Thyroid scan or ultrasound helpful in diagnosis||75%||Non-specific|
|Gallium scan positive||~100%||~100%|
|Barium swallow showing fistula||Common||0|
|CT scan useful||Varies||not indicated|
|Clinical Course||Clinical response to glucocorticoid treatment||Transient||100%|
|Incision and drainage required||85%||No|
|Recurrence following operative drainage||16%||No|
|Pyriform sinus fistula discovered||96%||No|
|Modified from Szabo and Allen (38), see also Shabb & Solti (186)|
Subacute Thyroiditis Case Illustration
A.S., a 46-year old woman, noted the onset of a tender, slowly enlarging swelling in the low anterior neck in December. There was no antecedent infection or virus-like syndrome. She was aware of associated increased nervousness, mild tremor, increased sweating, and anorexia, without alteration in weight. In January, increasing pain that radiated to the back of her head and orbits necessitated medical consultation. A family history of thyroid disease was not elicited.
On physical examination she appeared to be in pain, BP was 155/80, and pulse 112/min and regular. Clinically, she appeared to be euthyroid. The thyroid gland was estimated to be 40 grams in weight and was tender, firm, and slightly irregular. The remainder of the examination was non-contributory.
Laboratory data included an erythrocyte sedimentation rate of 58 mm/min, FT4I of 16.1 m g/dl (normal, 3.6 to 9.3 m g/dl), TT4 level of 14.9 m g/dl (normal 4.2 to 9.4), and a Tg antibody titer of 1/40 (negative).
Figure 3 (below) shows a sequence of 125 I and 241 Am scans obtained throughout the course of her illness. On presentation, there was no 125I uptake seen on thyroid scintiscan, with an RAIU of 1 percent. At the same time, the 241Am scan showed virtually no stable iodine in the thyroid. A 241Am scan repeated in March showed continuing low 127I levels in the thyroid, at which time the serum TT4 level was 1.7 mg/dl and the FT4I was 0.8 m g/dl. The 241Am scans on these two dates demonstrate mainly background radiation scatter. With the resolution of her clinical syndrome over the next few months, the results of the thyroid scans were seen to return to normal. The result of the 125I scintiscan in June was completely normal, with an RAIU of 20 percent, at which time her TT4 level and FT4I had returned to the normal range. The 241Am scan 3 months later showed some re-accumulation of 127I, but the stable iodine store was still reduced. The last 241Am scan 14 months after onset demonstrated total repletion of her thyroidal 127I stores. At this time, the gland was normal in size (weight 20 g) and consistency.
Figure 3. Serial 125 I scintiscans and 241 Am fluorescent scans in a patient during the course of subacute thyroiditis. The first two fluorescent scans, done at a high sensitivity setting without background subtraction, have much neck “background” but demonstrate virtually no 127 I in the thyroid. (From Rapoport et al, (166) with permission.)
If subacute thyroiditis affects only one part of the thyroid gland, the serum T4 concentration and thyroidal RAIU may be entirely normal. A thyroid scan done with either radioactive iodine of 99m-Tc-pertchnetate will demonstrate failure of the involved areas of the gland to concentrate the tracer. When the thyroid is diffusely involved, which is more typical, a dramatic disturbance in iodine metabolism is observed.
During the initial phase of the disease, the RAIU is depressed or entirely absent and the concentrations of serum T4 and T3 are often elevated. Due to the concomitant release of non-hydrolyzed iodoproteins from the inflamed tissue, the serum thyroglobulin level is also high. During this phase the serum TSH level is low. Analysis of the TSH suppression seen in thyrotoxic patients indicates that patients with SAT may demonstrate suppressed but detectable levels of TSH while those with Graves’ disease or silent thyroiditis have undetectable TSH values(187). As those with SAT are evaluated sooner in the course of thyrotoxicosis due to the pain of the condition, the duration of the thyrotoxicosis is less, leading to proportionally less TSH suppression. This finding has been proposed to be useful in the differential diagnosis of these thyrotoxic states(187). The TSH response to TRH is suppressed (164) due to the high levels of circulating thyroid hormone. Iodide that is collected and metabolized by the gland is rapidly secreted because of the decreased ability to store colloid (166). At this time, the involved tissue shows decreased but not necessarily depleted stores of iodine, as determined by x-ray fluorescence (163) , (166), a study which is not readily available in most clinical settings in the USA. Administration of TSH will fail to produce a normal increase in RAIU. Evidently, thyroid cell damage reduces the ability of the gland to respond to TSH. As the process subsides, the serum T4, T3, and TG levels decline, but the serum TSH level remains suppressed. The normal concentrations of SHBG sometimes observed in the thyrotoxic phase probably reflects the short duration of exposure to increased thyroid hormone (188). Later, during the recovery phase, the RAIU becomes elevated with the resumption of the ability of the thyroid gland to concentrate iodide. The serum T4 concentration may fall below normal; the TSH level may become elevated. Usually after several weeks or months, all the parameters of thyroid function return to normal (Fig.4). Restoration of iodine stores appears to be much slower and may take more than a year after the complete clinical remission (163) , (166). In about 2% of patients subacute thyroiditis may trigger auto-reactive B cells to produce TSH receptor antibodies, resulting in TSH antibody associated thyroid dysfunction in some patients (172). This finding may be a potential explanation of the apparent occurrence of Graves’ disease following an episode of SAT(189).
The patient presenting with painful neck symptoms is frequently empirically treated with antibiotics with minimal evaluation in general practice only later to be found to have thyroid related disease(178). Diagnosis is usually not difficult once the patient is seen by the specialist. With an acutely enlarged, tender thyroid, an RAIU near zero, and elevated serum T4, T3, thyroglobulin concentrations and ESR, the diagnosis is almost certain. Circulating thyroid autoantibodies are absent or the titer is low. Among the diagnostic alternatives, the uncommon presentation of thyrotoxicosis in infectious thyroiditis must be considered(29) and the possibility of invading bacteria excluded (see Table 2). Rarely a fever of unknown origin may suggest temporal arteritis but is actually due to subacute thyroiditis (160). Additionally, because of the radiation of painful thyroid into the jaw area the presence of dental pain may be confused with SAT(190). The thyroid in Hashimoto’s thyroiditis (HT) may be slightly tender and painful, but this event is rare, and the typical disturbances in iodine metabolism and erythrocyte sedimentation rate are rarely found. Markers of inflammation such as CRP as measured in the saliva are normal in HT when compared to controls but are grossly elevated in the patient with SAT(170).
Standard thyroid ultrasonography may appear similar with hypoechoic tissue in both HT and SAT but by sonoelastography the SAT gland is profoundly stiffer than HT tissue which is somewhat stiffer than normal controls(86). The radio nuclide thyroid uptake and scanning in HT is variable with elevated, depressed or normal results reported. 18 F-FDG-PET in Hashimoto’s on the other hand is similar to that seen in SAT with usually very positive uptake reported(191) , (179) , (192). Magnetic resonance imaging does not differentiate between HT and SAT(184) and is therefore, like 123-I and PET scanning, of little value in separating the patient with painful Hashimoto’s from the SAT patient.
Hemorrhage into a cyst in a nodular thyroid gland may be confused with subacute thyroiditis although the condition may be associated with an autonomously functioning nodule (193). Hemorrhage is usually more sudden and transient, a fluctuant mass may be found in the involved region, and the erythrocyte sedimentation rate is normal. Occasionally, subacute thyroiditis mimics hyperthyroidism in a patient whose RAIU is suppressed by the administration of exogenous iodine. This event occurs particularly in transient thyrotoxicosis induced by iodine (167). The sudden onset of subacute thyroiditis, the presence of toxic symptoms without the typical signs of long-term hyperthyroidism, the tender gland, the constitutional symptoms, and the high erythrocyte sedimentation rate are helpful in making the differentiation. In some instances, measurement of antibodies and thyroid-stimulating immunoglobulins, and observation of the course of the illness may be required to confirm the diagnosis.
The single disease entity that is probably most difficult to differentiate from subacute thyroiditis is a variant of lymphocytic thyroiditis (168). This condition is unrelated to iodine ingestion and most likely is a variant of autoimmune thyroiditis. The patient presents with goiter, mild thyrotoxicosis, and a low RAIU. The course of the disease is indistinguishable from that of subacute thyroiditis and proceeds from a thyrotoxic phase through a hypothyroid phase to spontaneous remission with normalization of thyroid function. The goiter is however, typically painless and there are no associated systemic symptoms. This condition has been formerly confused with subacute (de Quervain’s) thyroiditis, which likely has led to the descriptive terms of silent, painless, or atypical subacute thyroiditis to refer to this entity. The most helpful distinguishing features, short of histologic examination of biopsy material, are the absence of pain and a normal erythrocyte sedimentation rate. (See also Chapter 13.)
Localized subacute thyroiditis, with induration, mild tenderness, and depressed iodine binding visualized on scan, can clearly be very suggestive of acute suppurative thyroiditis or even thyroid cancer. One series indicated a surprisingly high frequency of focal involvement observed among those with SAT(181). Indeed this differential is quite difficult when incidentally discovered lesions are evaluated. Thyroid lesions incidentally identified by 18F-FDG-PET/CT are said to have malignant potential in 14-63% of lesions identified(194) , (195). Among the other diagnostic findings reported to account for such FDG-PET incidentalomas is focal SAT(185). Usually the degree of pain and tenderness, elevated erythrocyte sedimentation rate, leukocytosis, and remission or spread to other parts of the gland make clinical differentiation possible. Traditional ultrasonography may reveal localized hypoechoic area in the thyroid and gray-scale and color Doppler sonography may be helpful in this situation (180) , (196). Sonoelastography of these nodular lesions yields abnormally inelastic results in both SAT as well as thyroid cancer(197). Occasionally, magnetic resonance imaging (184), where the image of SAT is characterized by low intensity, may assist the clinician in differential of these nodular lesions. The hypoechoic area can reflect the degree of inflammation and thyroid hormone levels (182). However, a fine needle aspiration is required for a definitive differentiation between these two processes (193) as well as the other entities noted above(97).
In some patients with SAT, no treatment is required. However, for many, some form of analgesic therapy is required to treat the symptoms of the disease until it resolves. At times, this relief of symptoms can be achieved with non-steroidal anti-inflammatory agents or aspirin. However, if this fails, as it often does when the symptoms are severe, and after acute suppurative thyroiditis had been definitively ruled out as outlined above, prednisone administration should be employed (37) , (101). Large doses promptly relieve the symptoms through non-specific anti-inflammatory effects. Treatment is generally begun with a single daily dose of 40 mg prednisone. After one week of this treatment, the dosage is tapered over a period of 6 weeks or so. The relief of the tenderness in the neck is so dramatic as to be virtually diagnostic of subacute thyroiditis. As the dose is tapered, most patients have no recrudescence of symptoms, but occasionally this does occur and the dose must be increased again. Alternatively oral cholecystographic agents (such as sodium ipodate or sodium iopanoate [neither of which is available in the USA at present]) may be used safely and effectively for the management of the thyrotoxicosis in these patients even when they have relapsed after corticosteroid therapy (198). The recurrent rate of subacute thyroiditis after cessation of prednisolone therapy is about 20% but no difference has been found in routine laboratory data between recurrent and non-recurrent groups of patients (199). Levothyroxine administration has been touted as useful in situations where the patient is not already hyperthyroid due to the release of thyroidal contents into the circulation(101). The effectiveness of this strategy on shortening the clinical course or reducing the frequency of reoccurrence is not clear. It is also of course necessary to administer thyroid hormones, at least transiently, if the patient enters a phase of symptomatic hypothyroidism subsequent to the acute inflammation. Levothyroxine should only be administered for up to a year, otherwise, the return of thyroid function to normal, which presumably is facilitated by TSH, may be prevented or delayed. During the recovery process, there may be a marked but transient increase in the 24 hour radioactive iodine uptake which can reach levels typical of Graves’ disease but thyrotoxicosis is not simultaneously present. This elevation of iodine uptake occurs prior to re-establishment of normal thyroid function and should not be confused (taken out of context) with hyperthyroidism due to Graves’ Disease. Surgical intervention is not the primary treatment for subacute thyroiditis. Experience from the Mayo clinic (200) has shown however that if surgery is performed for a clinically indeterminate thyroid nodule, resection is safe and with low morbidity. Because of the possibility of associated papillary cancer further cytological examination should be performed in patients presenting with a persistent hypoechoic area larger than 1 cm by ultrasonography (183).
In 90% or more of patients, there is a complete and spontaneous recovery and a return to normal thyroid function. However, the thyroid glands of patients with subacute thyroiditis may exhibit irregular scarring between islands of residual functioning parenchyma, although the patient has no symptoms. Up to 10% of the patients may become hypothyroid and require permanent replacement with levothyroxine. In a retrospective study of 252 patients with SAT permanent hypothyroidism occurred in 5.9% and all these had bilateral hypoechogenic areas on thyroid ultrasound at initial presentation suggesting that this may be a useful prognostic marker for the potential development of thyroid dysfunction after SAT (201). However, permanent hypothyroidism is significantly less common in SAT compared to the outcome noted in amiodarone induced thyrotoxicosis type 2 (the destructive thyroiditis) (202). It is of interest that elevated levels of serum thyroglobulin may persist well over a year after the initial diagnosis, indicating that disordered follicular architecture and/or low grade inflammation can persist for a relatively long period (203).
A minority (< 1%) of those presenting with clinical SAT in Japan have been recently reported to return (n= 7) a mean 4.7 months later with findings consistent with Graves’ disease(189) (GD). Review of the other 26 cases summarized in the report of Nakano et al. indicates a similar interval between the diagnosis of SAT and subsequent GD presentation, a clearly elevated RAIU in the GD phase of all the reports where an uptake is reported (14/26 [54%]) and a change in thyroid antibody positivity in 50% of those evaluated in both (6/26 [23%]) the SAT and GD presentation(189). Combining Nakano’s cases with their review of the literature, fully 21/31 [68%] of cases labeled as SAT were diagnosed clinically without a radioactive iodine uptake assessment and a further 4/12 [33%] of those diagnosed as SAT with a RAIU available, had uptakes greater than 10% at the time of the SAT diagnosis(189). This brings into question the true incidence of this reported transition from presumably non-autoimmune SAT to clearly immune mediated GD.
Initially described by Semple in 1864 and Bolby in 1888(204), the condition then again reported in 1896 by Riedel as an “eisenharte” (iron hard) fixed and usually painless enlargement of the thyroid (205-207) is a chronic sclerosing thyroiditis, occurring especially in women, that tends to progress inexorably to complete destruction of the thyroid gland and frequently causes pressure symptoms in the neck (208) , (205) , (209). It is exceedingly rare with estimated incidence of 1.06 cases per 100,000 population and 37/57,000 (0.06%) surgical outcomes over a 64 year period(210). In the Mayo Clinic series (210) it occurred approximately one-fiftieth as frequently as Hashimoto’s thyroiditis. It is more frequent in women (F:M 3.1:1)(211) , (117) , (205) , (37) who were recently reported to represent 81% of those with confirmed Riedel’s in a Mayo clinic series(212). Riedel’s thyroiditis is principally reported to occur in the 30- to 50 year age group(212) , (211) , (37).
The thyroid gland is normal in size or enlarged, focally or symmetrically involved, and extremely (woody) hard. The gland is replaced by the inflammatory process which may extend into adjacent structures including parathyroid, skeletal muscle, nerves, blood vessels as well as the trachea(213). Gross observation of the mass reveals a pale gray appearance similar to a malignant lesion(214). There are no tissues planes visible and the cut surface of the mass is stark white due to the hypovascularity of the tissue(215). Histologically normal tissue is replaced by inflammatory cells, predominantly lymphocytes, plasma cells, eosinophils(211) , (216),and small amounts of colloid(217-219) in a dense matrix of hyalinized connective tissue. Characteristically, an inflammatory reaction of the venous vascular structures has been described(214). An oft stated criterion useful in assuring the pathologic diagnosis is to note the absence of granulomatous tissue and malignancy(214) , (211) , (215). A potentially difficult differential diagnostic decision may be encountered with rare sarcomas of the thyroid region(220) or with the pauci-cellular variant of anaplastic thyroid cancer which although similar in gross appearance will have distinctive histopathologic immunohistochemical findings(221).
Although the etiology is unclear, Riedel’s has been characterized in various ways including as the cervical manifestation of a systemic fibrosing disorder with identical histopathological appearance(222). Further Riedel’s has been called a variant of Hashimoto’s, a primary infiltrative disease of the thyroid and even a manifestation of end stage deQuervain’s thyroiditis(223) , (208) , (224) , (219). Riedel’s has been reported following subacute thyroiditis (223) and a case of concurrent Riedel’s, Hashimoto’s and acute thyroiditis has also been reported (225). The report of a case of Graves’ disease following Riedel’s thyroiditis (226) and the observation that the B cell proliferation observed in the course of these diseases has been shown to be polyclonal (227) supports the notion of autoimmune mechanisms in the etiology of the Riedel’s condition. The occurrence of marked tissue eosinophilia and the extracellular deposition of eosinophil granule major basic protein suggests a role for eosinophils and their products in the development of fibrosis in Riedel’s thyroiditis (216). Fibrosis may also be related to the action of TGF beta 1, as seen in murine thyroiditis (228). Most recently links between Hashimoto’s, IgG4-related systemic disease (IgG4-RSD) and Riedel’s have been reported (229-231). Supporting evidence showing the presence of IgG4-bearing plasma cells in thyroidectomy specimens and other affected organs (229) , (232). A recent comprehensive review of potential etiology has been published(213).
Riedel’s thyroiditis usually presents as a hard thyroid mass, frequently associated with compressive symptoms(208) , (212) , (211) , (210) , (233) , (205) , (37) and historically has been diagnosed by a surgeon faced with an inflammatory mass of fibrosclerosing tissue(234) , (235) when expecting a thyroid tumor(218). Intraoperative diagnostic confusion with anaplastic thyroid cancer(221), sarcoma of the thyroid(220), thyroid lymphoma(236) or fibrosing Hashimoto’s thyroiditis(237) have been reported. Riedel’s may occur in a multinodular goiter or as a rapidly growing hard neck mass in a previously normal gland mimicking thyroid cancer(234) , (238). As the extent of the fibrosis increases or concomitant Hashimoto’s is present, involvement of a critical mass of the thyroid tissue results in primary hypothyroidism in 25-80% of cases(217) , (239) , (208) , (212) , (218). Antithyroid antibodies are present in 67-90% of reported cases(212) , (209). Extension of the inflammatory process into underlying parathyroid glands may result in non-surgical hypoparathyroidism(239-243) in up to 14% cases encountered(212). The fibrosis may remain relatively stable or progress resulting in local complications by compressing the trachea or esophagus and resulting in symptoms of local pressure, dyspnea, dysphagia as well as stridor out of proportion of the size of the mass(244) , (245), with subsequent hoarseness, and aphonia, with involvement of the recurrent laryngeal nerves(237) , (243). Further extension of the inflammatory process involving neck structure can result in Tolosa-Hunt syndrome(246), Horner’s syndrome(243), occlusive phlebitis of cervical vessels(247-249). The occurrence of cerebral sinus thrombosis suggests that Riedel’s thyroiditis may cause venous stasis, vascular damage, and possibly hypercoaguability (250). Estimates as high as 38% associate Riedel’s thyroiditis with similar fibro-sclerotic processes in other areas(212). Subcutaneous fibrosclerosis has also been noted but it is very rare(251). The lesions appear in the lacrimal glands, orbits(252), parotid glands(253), mediastinum(214) , (212) , (210) , (218), coronary arteries(212), retroperitoneal tissues(239) , (208) , (210) , (254) , (255), bile ducts(256) , (211) and pancreas(256) in varying combinations in the syndrome of multifocal fibro-sclerositis (257) , (258).
Initially the patient with a thyroid mass will need an assessment of thyroid function, and may benefit from screening thyroid antibodies(259). A complete blood count reveals normal to elevated white blood cell counts. The erythrocyte sedimentation rate is usually moderately elevated(218) , (219). Due to the potential of hypoparathyroidism an assessment of calcium status is prudent(213). Ultrasonography of the thyroid typically reveals a diffuse, hypoechoic, hypovascular appearance due to the extensive fibrosing process(234) , (239) , (226) , (260) , (261). Unique to the findings in Riedel’s thyroiditis is an encasement of the carotid arteries, not typically seen in other forms of multinodular or Hashimoto’s goiter(212) , (262). Sonographic elastography demonstrates significant stiffness of the tissue compared to normal thyroid(262). At this point in the evaluation a fine needle aspiration (FNA) of the thyroid mass is usually obtained. FNA results are typically non-diagnostic due the lack of thyroid follicular cells(212) , (211) , (215) , (37) but may contain evidence of the inflammatory process(212), fibrous tissue and myofibroblasts(263), or even cytopathology findings consistent with follicular neoplasm(241).
In patients with significant obstructive symptomatology a neck computed tomography (CT) study may be ordered to assess tracheal integrity. CT images characteristically demonstrate hypodense tissue which does not enhance with iodinated contrast in the affected area(260). CT images readily reveal extrathyroidal extension of the inflammatory process(260) , (264), and have been reported to document arterial encasement in about half of subjects and jugular involvement in about one third of cases(212). Magnetic resonance imaging (MRI) can be expected to show hypointense images on both T1 and T2 weighted images(260) and variable enhancement patterns after gadolinium enhancement(265) , (260) , (261) , (264) , (266). Unlike the hypointense images produced by CT and MRI, Fluorine-18 fluorodeoxyglucose [FDG] positron emission tomographic (PET) images have shown metabolic activity not only in extrathyroidal masses associated with the systemic inflammatory process but also increased glucose metabolism in the Riedel’s thyroid, likely as a result of active inflammation involving lymphocytes, plasma cells and fibroblast proliferation (267) , (268) , (262). FDG metabolic activity can also be used to assess a patient’s response to therapy (267) , (268) but not all reports of this phenomenon had documented this effect(262).
Although not typically indicated in the evaluation of a eu- or hypothyroid individual with a thyroid mass, 99mTc-pertechnetate or 123/131-I scanning in Riedel’s is typically compromised due to low uptake and patchy images typical of other forms of chronic thyroiditis(211) , (218) , (219). An exception to the utility of radio nuclide scanning is found in exactly the circumstance where a nuclear medicine scan is indicated that being in the thyrotoxic patient presenting with the thyroid mass. In those with Graves’ disease or a toxic thyroid nodule, the hyperfunctioning portion of the thyroid is indeed well visualized while the portion involved with Riedel’s typically demonstrates no uptake(226). Finally, it has recently been reported that gallium scanning may. As expected, also demonstrate significant uptake in the Riedel’s lesion(88).
Establishing the diagnosis of Riedel’s requires histopathologic confirmation at the present time. Biopsy material may be obtained by Tru-cut needle biopsy(269), open biopsy(37) or at the time of decompressive thyroidectomy. Histopathologic findings required to establish this diagnosis include: 1) The presence of an inflammatory process in the thyroid with extension into surrounding tissue. 2) The inflammatory infiltrate should contain no giant cells, lymphoid follicles, oncocytes or granulomas. 3) There should be evidence of occlusive phlebitis. 4) There should be no evidence of thyroid malignancy(270). In light of the recent work defining Riedel’s as a potential manifestation of the IgG4-related systemic sclerosing disease, the potential role of incorporating the presence of immunohistochemical assessment of tissue lymphocytes and the measurement of IgG4 levels into working diagnostic criteria remains to be defined.
Management of Riedel’s Thyroiditis
Although there is no specific therapy for Riedel’s thyroiditis, several management strategies are available dependent on the clinical features of the disease in the individual patient. Patients commonly undergo surgery for relief of obstructive symptoms. Histopathology allows for the definitive establishment of the diagnosis. Most are then treated medically for associated hormone deficiencies with levothyroxine and /or calcium along with with calcitriol, but this supplementation is not thought to influence the course of the disease. Finally, anti-inflammatory treatment aimed at diminishing the inflammatory mass is applied.
Surgical therapy for debulking and symptoms relief should usually be limited to isthmusectomy (211) , (241) , (233) , (37) when total thyroidectomy is not possible. Due to the obliteration of tissue planes associated with the advancing inflammatory process there is an enhanced danger of hypoparathyroidism and recurrent laryngeal nerve injury even when limited surgery is performed by experienced surgical specialists as documented in a recent series from the Mayo clinic where 39% of Riedel’s patients suffered surgical complications(212). Previous and contemporary experience therefore recommends that extensive surgical procedures be considered inappropriate (212) , (215) , (241) , (37).
Medical therapy to arrest progression of symptomatic disease should be pursued after establishment of a firm diagnosis. Corticosteroid therapy has been found to be effective in some cases (271) , (240) , (272) , (265) , (269) , (258) , (273-275) , (250) , (276) , (209), probably those with active inflammation(229) , (274). Initial doses of up to 100mg per day of prednisone have been used(211) but sustained improvement has been reported with lower doses of 15-60 mg per day (271) , (258) , (273) , (276) , (236) , (243). There are no controlled trials of steroid therapy in Riedel’s and although some patients obtain long term benefit after steroid withdrawal (222) , (258) , (274) others may relapse usually leading to the reintroduction of glucocorticoids or the addition of alternative anti-inflammatory therapy(277) , (278) , (243). The reasons for this variation are unclear but inflammatory activity and duration of disease may be relevant factors. Most recently, the observation that smoking history may play a role in the responsiveness of Riedel’s pathology to glucocorticoid therapy has been published(212).
In those who fail to respond to steroid therapy or relapse after withdrawal, tamoxifen therapy should be tried. Several reports have described an encouraging response with this agent, admittedly in only a small number of patients (279-282) , (277) , (283) , (284) , (243). It is possible that tamoxifen acts in Riedel’s by inhibition of fibroblast proliferation through the stimulation of TGF beta (285-287). Tamoxifen in combination with prednisone or tamoxifen as monotherapy have both been reported to be effective (277) , (283) , (284) , (243). There appears to be a persistent benefit to tamoxifen therapy during continued application in most but not all cases (212) , (278). Recent data on effective therapy with other immunosuppressive agents indicates that a combination of mycophenolate mofetil and prednisone has been observed to have successfully treated an individual who failed a prednisone and tamoxifen combination (278). The potential usefulness of this intervention awaits confirmation.
Summary of Riedel’s Thyroiditis
Riedel’s thyroiditis should be suspected in patients with a thyroid mass and unique clinical features. Findings increasing the likelihood of Riedel’s include local restrictive or infiltrative symptoms out of proportion to the size or extent of the mass or simultaneous hypocalcemia. Surgical intervention should be limited to rule out the presence of malignancy and obtain the histopathologic confirmation. Once Riedel’s thyroiditis is established, a search for related fibrotic conditions and medical treatment should be pursued. Replacement of thyroxine and when appropriate, calcium and vitamin D therapy should be begun along with anti-inflammatory medications.
RARE INFLAMMATORY OR INFILTRATIVE DISEASES
In addition to the varieties of thyroiditis already mentioned, which are diseases specifically of the thyroid gland, generalized or systemic diseases may also involve the thyroid gland (37). The lesions of sarcoid may appear in the thyroid gland of 1-4% 0f patients with systemic sarcoidosis(288). Thyroid dysfunction has been reported very infrequently (1-3%)(289) in systemic sarcoidosis but a recent series of patients with cutaneous sarcoidosis noted abnormal TSH values in 26% compared to the US population expectation of about 10%(289). Most thyroid dysfunction was mild, a male to female ratio of abnormal thyroid function of 1:1 was noted, Caucasians were more frequently affected than African Americans and 20% of those with abnormal TSH were classified as hypothyroid(289). Infiltration of the thyroid with sarcoidosis is reported to occur in about 5% of patients with sarcoidosis(290). Multinodular goiter has recently been described as an initial presenting manifestation in a woman eventually diagnosed with systemic sarcoidosis(288). This case illustrates the difficulty in diagnosing the cause of supine dyspnea in patients with sarcoidosis, illustrating the potential of a thyroid contribution to the overall clinical picture(288).
Deposits of amyloid are quite common in systemic amyloidosis(291) and rarely causes goiter with more than 200 cases in the worlds literature(292) , (291) , (293) , (294). Although senile transthyretin amyloidosis is primarily associated with amyloid deposits in the heart, familial forms of amyloidosis due to transthyretin gene mutations are associated with deposits of amyloid in multiple tissues(295) . Amyloid goiter with transthyretin activity in a patient with chronic renal failure has been reported (295). Clinically, an amyloid goiter may be progressive, diffuse and rapidly lead to compressive symptoms(291) , (294). Thyroid function in association with an amyloid goiter is normal in 2/3 of cases, 1/7 present with hypothyroidism and fewer demonstrate other abnormalities of thyroid function(291). In addition to the focal deposition of amyloid in thyroid tissues associated with most cases of medullary thyroid cancer(296), several cases of papillary thyroid cancer have been reported in association of amyloid goiter(297-299) , (291). Amyloid goiter may be readily diagnosed by fine needle aspiration biopsy(300) and has been reported in conjunction with infiltration of other endocrine organs such as the pituitary(293). It has been suggested that the thyroid FNA is both an accurate and relatively safe site of biopsy to confirm the presence of systemic amyloidosis(291).
Painless thyroiditis has been noted in a woman with rheumatoid arthritis and secondary amyloidosis infiltrating the thyroid gland (301). Radiotherapy for tonsillar carcinoma has been reported to result in thyroiditis (302). Irradiation to the thyroid during therapy for breast cancer or lymphoma can also induce hypothyroidism. Following 131 I therapy for Graves’ disease or toxic multinodular goiter, thyroiditis which is occasionally symptomatic, may develop. This situation is discussed in Chapters 11 and 18. Therapy should be directed toward the primary disease rather than the thyroid, but administration of thyroid hormone may be necessary if destruction of thyroid tissue is sufficient to produce hypothyroidism. Finally, surgery to the neck, associated with mechanical manipulation of the thyroid during laryngectomy or parathyroid surgery can result in a painless subacute thyroiditis like picture (303-305).
SUMMARY: THYROIDITIS, ACUTE, SUBACUTE AND RIEDEL’S
The thyroid, like any other structure, may be the seat of an acute or chronic suppurative or non-suppurative inflammation. Various systemic infiltrative disorders may leave their mark on the thyroid gland as well as elsewhere. Infectious thyroiditis is a rare condition, usually the result of bacterial invasion of the gland. Its signs are the classic ones of inflammation: heat, pain, redness, and swelling, and special ones conditioned by local relationships, such as dysphagia and a desire to keep the head flexed on the chest in order to relax the paratracheal muscles. The treatment is that for any febrile disease, including specific antibiotic drugs if the invading organism has been identified and its sensitivity to the drug established. Otherwise, a broad-spectrum antibiotic may be used. Surgical drainage may be necessary and a search for a pyriform sinus fistula should be made, particularly in children with thyroiditis involving the left lobe. Important to differentiate from the acute bacterial infection of acute suppurative thyroiditis (AST) is subacute (granulomatous) thyroiditis (SAT) which is far more common than AST and is characterized by a more protracted course, usually involving the thyroid symmetrically. The gland is also swollen and tender, and the systemic reaction may also be severe, with fever and an elevated erythrocyte sedimentation rate. During the acute phase of the disorder, tests of thyroid function disclose a suppression of TSH, increased serum concentrations of T4, T3, and thyroglobulin while a diminished thyroidal RAIU is observed. The cause of SAT has been established in only a few instances in which a viral infection has been the initiating factor. There may be repeated recurrences of diminishing severity. Usually, but not always, the function of the thyroid is normal after the disease has subsided. Subacute thyroiditis may be treated with rest, non-steroidal anti-inflammatory drugs or aspirin, and thyroid hormone. If the disease is severe and protracted, it is usually necessary to resort to administration of glucocorticoids, but recurrence may follow their withdrawal. It is precisely the observational nature of SAT therapy combined with the use of glucocorticoids which make it so critical to definitively rule out the bacterial etiology of AST in the patient presenting with a painful thyroid.
Riedel’s thyroiditis is a chronic sclerosing replacement of the gland that is exceedingly rare. The process extends to adjacent structures, making any surgical intervention very difficult and potentially harmful. The exact cause of Riedel’s thyroiditis remains unknown, and no specific treatment is available beyond limited resection of the thyroid gland to relieve the symptoms of tracheal or esophageal compression. The use of anti-inflammatory medical treatments has been demonstrated to have significant benefits to outcome. Sarcoidosis may involve the thyroid, and amyloid may be deposited in the gland in quantities sufficient to cause goiter. In all of these diseases it may be necessary to give the patient levothyroxine replacement therapy if the function of the gland has been impaired.
1. Brook, I 2003 Microbiology and management of acute suppurative thyroiditis in children Int J Pediatr Otorhinolaryngol 67 :447-451.
2. Chang, P, Tsai, WY, Lee, PI, Hsiao, PH, Huang, LM, Lee, JS, Peng, SF Li, YW 2002 Clinical characteristics and management of acute suppurative thyroiditis in children J Formos Med Assoc 101 :468-471.
3. Chi, H, Lee, YJ, Chiu, NC, Huang, FY, Huang, CY, Lee, KS, Shih, SL Shih, BF 2002 Acute suppurative thyroiditis in children Pediatr Infect Dis J 21 :384-387.
4. Hatabu, H, Kasagi, K, Yamamoto, K, Iida, Y, Misaki, T, Hidaka, A, Endo, K Konishi, J 1990 Acute suppurative thyroiditis associated with piriform sinus fistula: sonographic findings AJR Am J Roentgenol 155 :845-847.
5. Fukata, S, Miyauchi, A, Kuma, K Sugawara, M 2002 Acute suppurative thyroiditis caused by an infected piriform sinus fistula with thyrotoxicosis Thyroid 12 :175-178.
6. Gan, YULam, SL 2004 Imaging findings in acute neck infection due to pyriform sinus fistula Ann Acad Med Singapore 33 :636-640.
7. Lucaya, J, Berdon, WE, Enriquez, G, Regas, J Carreno, JC 1990 Congenital pyriform sinus fistula: a cause of acute left-sided suppurative thyroiditis and neck abscess in children Pediatr Radiol 21 :27-29.
8. Miyauchi, A, Matsuzuka, F, Kuma, K Katayama, S 1992 Piriform sinus fistula and the ultimobranchial body Histopathology 20 :221-227.
9. Miyauchi, A, Yokozawa, T, Matsuzuka, F Kuma, K 1998 Acute suppurative thyroiditis; infection in thyroid nodules or infection through a piriform sinus fistula. Thyroidol. Clin Exp 10 :75-79.
10. Shah, SSBaum, SG 2000 Diagnosis and Management of Infectious Thyroiditis Curr Infect Dis Rep 2 :147-153.
11. Paes, JE, Burman, KD, Cohen, J, Franklyn, J, McHenry, CR, Shoham, S Kloos, RT 2010 Acute bacterial suppurative thyroiditis: a clinical review and expert opinion Thyroid 20 :247-255.
12. Hendrick, JW 1957 Diagnosis and management of thyroiditis J Am Med Assoc 164 :127-133.
13. Yu, EH, Ko, WC, Chuang, YC Wu, TJ 1998 Suppurative Acinetobacter baumanii thyroiditis with bacteremic pneumonia: case report and review Clin Infect Dis 27 :1286-1290.
14. Minhas, SS, Watkinson, JC Franklyn, J 2001 Fourth branchial arch fistula and suppurative thyroiditis: a life-threatening infection J Laryngol Otol 115 :1029-1031.
15. Nicoucar, K, Giger, R, Pope, HG, Jr., Jaecklin, T Dulguerov, P 2009 Management of congenital fourth branchial arch anomalies: a review and analysis of published cases J Pediatr Surg 44 :1432-1439.
16. Acocelia, A, Nardi, P, Sacco Agostini, T 2007 Acute thyroiditis of odontogenic origin. Minerva Stomatol. 56 :461-467.
17. Berger, SA, Zonszein, J, Villamena, P Mittman, N 1983 Infectious diseases of the thyroid gland Rev Infect Dis 5 :108-122.
18. Fernandez, JF, Anaissie, EJ, Vassilopoulou-Sellin, R Samaan, NA 1991 Acute fungal thyroiditis in a patient with acute myelogenous leukaemia J Intern Med 230 :539-541.
19. Gandhi, RT, Tollin, SR Seely, EW 1994 Diagnosis of Candida thyroiditis by fine needle aspiration J Infect 28 :77-81.
20. Vandjme, A, Pageaux, GP, Bismuth, M, Fabre, JM, Domergue, J, Perez, C, Makeieff, M, Mourad, G Larrey, D 2001 Nocardiosis revealed by thyroid abscess in a liver–kidney transplant recipient Transpl Int 14 :202-204.
21. Imai, C, Kakihara, T, Watanabe, A, Ikarashi, Y, Hotta, H, Tanaka, A Uchiyama, M 2002 Acute suppurative thyroiditis as a rare complication of aggressive chemotherapy in children with acute myelogeneous leukemia Pediatr Hematol Oncol 19 :247-253.
22. Bukvic, B, Diklic, A Zivaljevic, V 2009 Acute suppurative klebsiella thyroiditis: a case report Acta Chir Belg 109 :253-255.
23. Chiovato, L, Canale, G, Maccherini, D, Falcone, V, Pacini, F Pinchera, A 1993 Salmonella brandenburg: a novel cause of acute suppurative thyroiditis Acta Endocrinol (Copenh) 128 :439-442.
24. Dai, MS, Chang, H, Peng, MY, Ho, CL Chao, TY 2003 Suppurative salmonella thyroiditis in a patient with chronic lymphocytic leukemia Ann Hematol 82 :646-648.
25. Su, DHHuang, TS 2002 Acute suppurative thyroiditis caused by Salmonella typhimurium: a case report and review of the literature Thyroid 12 :1023-1027.
26. Wu, SW, Chang, HR, Tsao, SM, Wu, YL, Yao, CC Lian, JD 2008 A Salmonella infection complicated with suppurative thyroiditis and ruptured aortic mycotic aneurysm in a renal transplant recipient Transplant Proc 40 :3759-3763.
27. Fernandez Pena, C, Morales Gorria, MJ, Morano Amado, LE, Lopez Miragalla, MI Pena Gonzalez, E 1999 Pasteurella spp: a newmicroorganism to the cause of acute suppurative thyroiditis. An Med Interna 16 :637-638.
28. McLaughlin, SA, Smith, SL Meek, SE 2006 Acute suppurative thyroiditis caused by Pasteurella multocida and associated with thyrotoxicosis Thyroid 16 :307-310.
29. Spitzer, M, Alexanian, S Farwell, AP 2011 Thyrotoxicosis with Post-Treatment Hypothyroidism in a Patient with Acute Suppurative Thyroiditis Due to Porphyromonas Thyroid.
30. Iniguez, JL, Duyckaerts, V Badoual, J 1989 [Acute thyroiditis caused by Eikenella corrodens and abnormality of the left pyriform sinus] Arch Fr Pediatr 46 :745-747.
31. Queen, JS, Clegg, HW, Council, JC Morton, D 1988 Acute suppurative thyroiditis caused by Eikenella corrodens J Pediatr Surg 23 :359-361.
32. Yoshino, Y, Inamo, Y, Fuchigami, T, Hashimoto, K, Ishikawa, T, Abe, O, Tahara, D Hayashi, K 2010 A pediatric patient with acute suppurative thyroiditis caused by Eikenella corrodens J Infect Chemother 16 :353-355.
33. Das, DK, Pant, CS, Chachra, KL Gupta, AK 1992 Fine needle aspiration cytology diagnosis of tuberculous thyroiditis. A report of eight cases Acta Cytol 36 :517-522.
34. Nieuwland, Y, Tan, KY Elte, JW 1992 Miliary tuberculosis presenting with thyrotoxicosis Postgrad Med J 68 :677-679.
35. Orlandi, F, Fiorini, S, Gonzatto, I, Saggiorato, E, Pivano, G, Angeli, A Pasquali, R 1999 Tubercular involvement of the thyroid gland: a report of two cases Horm Res 52 :291-294.
36. Terzidis, K, Tourli, P, Kiapekou, E Alevizaki, M 2007 Thyroid tuberculosis Hormones (Athens) 6 :75-79.
37. Singer, PA 1991 Thyroiditis. Acute, subacute, and chronic Med Clin North Am 75 :61-77.
38. Szabo, SMAllen, DB 1989 Thyroiditis. Differentiation of acute suppurative and subacute. Case report and review of the literature Clin Pediatr (Phila) 28 :171-174.
39. Karatoprak, N, Atay, Z, Erol, N, Goksugur, SB Ceran, O 2005 Actinomycotic suppurative thyroiditis in a child J Trop Pediatr 51 :383-385.
40. Moinuddin, S, Barazi, H Moinuddin, M 2008 Acute blastomycosis thyroiditis Thyroid 18 :659-661.
41. Park, YH, Baik, JH Yoo, J 2005 Acute thyroiditis of actinomycosis Thyroid 15 :1395-1396.
42. Trites, JEvans, M 1998 Actinomycotic thyroiditis in a child J Pediatr Surg 33 :781-782.
43. Carriere, C, Marchandin, H, Andrieu, JM, Vandome, A Perez, C 1999 Nocardia thyroiditis: unusual location of infection J Clin Microbiol 37 :2323-2325.
44. Karabinis, A, Douzinas, E, Clouva, P, Papanicolaou, M, Kakaviatos, N Bilalis, D 1993 [Acute necrotic thyroiditis caused by Candida albicans immediately after acute hemorrhagic rectocolitis] Presse Med 22 :34.
45. Lewin, SR, Street, AC Snider, J 1993 Suppurative thyroiditis due to Nocardia asteroides J Infect 26 :339-340.
46. Avram, AM, Sturm, CA, Michael, CW, Sisson, JC Jaffe, CA 2004 Cryptococcal thyroiditis and hyperthyroidism Thyroid 14 :471-474.
47. Zavascki, AP, Maia, AL Goldani, LZ 2007 Pneumocystis jiroveci thyroiditis: report of 15 cases in the literature Mycoses 50 :443-446.
48. Orkar, KS, Dakum, NK, Kidmas, AT Awani, KU 2001 Pyogenic thyroiditis and HIV infection West Afr J Med 20 :173-175.
49. Tien, KJ, Chen, TC, Hsieh, MC, Hsu, SC, Hsiao, JY, Shin, SJ Hsin, SC 2007 Acute suppurative thyroiditis with deep neck infection: a case report Thyroid 17 :467-469.
50. Iwama, S, Kato, Y Nakayama, S 2007 Acute suppurative thyroiditis extending to descending necrotizing mediastinitis and pericarditis Thyroid 17 :281-282.
51. Premawardhana, LD, Vora, JP Scanlon, MF 1992 Suppurative thyroiditis with oesophageal carcinoma Postgrad Med J 68 :592-593.
52. Valina, S, Lotter, O, Schaller, HE Rahmanian-Schwarz, A 2011 [Abscess Formation after Puncture of a Thyroid Cyst – A Case Report.] Zentralbl Chir.
53. Kale, SU, Kumar, A David, VC 2004 Thyroid abscess–an acute emergency Eur Arch Otorhinolaryngol 261 :456-458.
54. Jimenez-Heffernan, JA, Perez, F, Hornedo, J, Perna, C Lapuente, F 2004 Massive thyroid tumoral embolism from a breast carcinoma presenting as acute thyroiditis Arch Pathol Lab Med 128 :804-806.
55. Nishihara, E, Miyauchi, A, Matsuzuka, F, Sasaki, I, Ohye, H, Kubota, S, Fukata, S, Amino, N Kuma, K 2005 Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis Thyroid 15 :1183-1187.
56. Chen, HW, Tseng, FY, Su, DH, Chang, YL Chang, TC 2006 Secondary infection and ischemic necrosis after fine needle aspiration for a painful papillary thyroid carcinoma: a case report Acta Cytol 50 :217-220.
57. Sicilia, VMezitis, S 2006 A case of acute suppurative thyroiditis complicated by thyrotoxicosis J Endocrinol Invest 29 :997-1000.
58. Hopwood, NJKelch, RP 1993 Thyroid masses: approach to diagnosis and management in childhood and adolescence Pediatr Rev 14 :481-487.
59. Sai Prasad, TR, Chong, CL, Mani, A, Chui, CH, Tan, CE, Tee, WS Jacobsen, AS 2007 Acute suppurative thyroiditis in children secondary to pyriform sinus fistula Pediatr Surg Int 23 :779-783.
60. Wasniewska, M, Vigone, MC, Cappa, M, Cassio, A, Scognamillo, R, Aversa, T, Rubino, M De Luca, F 2007 Acute suppurative thyroiditis in childhood: spontaneous closure of sinus pyriform fistula may occur even very early J Pediatr Endocrinol Metab 20 :75-77.
61. Dugar, M, da Graca Bandeira, A, Bruns, J, Jr. Som, PM 2009 Unilateral hypopharyngitis, cellulitis, and a multinodular goiter: a triad of findings suggestive of acute suppurative thyroiditis AJNR Am J Neuroradiol 30 :1944-1946.
62. Mohan, PS, Chokshi, RA, Moser, RL Razvi, SA 2005 Thyroglossal duct cysts: a consideration in adults Am Surg 71 :508-511.
63. Robazzi, TC, Alves, C Mendonca, M 2009 Acute suppurative thyroiditis as the initial presentation of juvenile systemic lupus erythematosus J Pediatr Endocrinol Metab 22 :379-383.
64. Cabizuca, CA, Bulzico, DA, de Almeida, MH, Conceicao, FL Vaisman, M 2008 Acute thyroiditis due to septic emboli derived from infective endocarditis Postgrad Med J 84 :445-446.
65. Inoue, K, Kozawa, J, Funahashi, T, Nakata, Y, Mitsui, E, Kitamura, T, Maeda, N, Kishida, K, Otsuki, M, Okita, K, Iwahashi, H, Imagawa, A Shimomura, I 2011 Right-sided acute suppurative thyroiditis caused by infectious endocarditis Intern Med 50 :2893-2897.
66. Bar-Ziv, J, Slasky, BS, Sichel, JY, Lieberman, A Katz, R 1996 Branchial pouch sinus tract from the piriform fossa causing acute suppurative thyroiditis, neck abscess, or both: CT appearance and the use of air as a contrast agent AJR Am J Roentgenol 167 :1569-1572.
67. Cases, JA, Wenig, BM, Silver, CE Surks, MI 2000 Recurrent acute suppurative thyroiditis in an adult due to a fourth branchial pouch fistula J Clin Endocrinol Metab 85 :953-956.
68. Himi, TKataura, A 1995 Distribution of C cells in the thyroid gland with pyriform sinus fistula Otolaryngol Head Neck Surg 112 :268-273.
69. Miyauchi, A, Matsuzuka, F, Takai, S, Kuma, K Kosaki, G 1981 Piriform sinus fistula. A route of infection in acute suppurative thyroiditis Arch Surg 116 :66-69.
70. Nonomura, N, Ikarashi, F, Fujisaki, T Nakano, Y 1993 Surgical approach to pyriform sinus fistula Am J Otolaryngol 14 :111-115.
71. Takai, SI, Miyauchi, A, Matsuzuka, F, Kuma, K Kosaki, G 1979 Internal fistula as a route of infection in acute suppurative thyroiditis Lancet 1 :751-752.
72. Yamashita, J, Ogawa, M, Yamashita, S, Saishoji, T, Nomura, K Tsuruta, J 1994 Acute suppurative thyroiditis in an asymptomatic woman: an atypical presentation simulating thyroid carcinoma Clin Endocrinol (Oxf) 40 :145-149; discussion 149-150.
73. Al-Kordi, RS, Alenizi, E Elgazzar, AH 2008 Acute suppurative thyroiditis with abscess, gas formation, and thyrotoxic crisis Nuklearmedizin 47 :N44-46.
74. Bussman, YC, Wong, ML, Bell, MJ Santiago, JV 1977 Suppurative thyroiditis with gas formation due to mixed anaerobic infection J Pediatr 90 :321-322.
75. Gaafar, HEl-Garem, F 1975 Acute thyroiditis with gas formation J Laryngol Otol 89 :323-327.
76. Reksoprawiro, S 2003 Suppurative thyroiditis with gas formation Asian J Surg 26 :180-182.
77. Dordain, ML, Coutant, G, Algayres, JP, Jancovici, R, Pats, B Daly, JP 1997 [Suppurative mediastinitis secondary to acute thyroiditis in a patient under corticotherapy] Presse Med 26 :319-320.
78. Lemariey, Hamelin Muler 1955 [Acute thyroiditis complicating mediastinitis] Ann Otolaryngol 72 :571-573.
79. Pereira, O, Prasad, DS, Bal, AM, McAteer, D Abraham, P 2010 Fatal descending necrotizing mediastinitis secondary to acute suppurative thyroiditis developing in an apparently healthy woman Thyroid 20 :571-572.
80. Larsen, PR 1975 Thyroidal triiodothyronine and thyroxine in Graves’ disease: correlation with presurgical treatment, thyroid status, and iodine content J Clin Endocrinol Metab 41 :1098-1104.
81. Yung, BC, Loke, TK, Fan, WC Chan, JC 2000 Acute suppurative thyroiditis due to foreign body-induced retropharyngeal abscess presented as thyrotoxicosis Clin Nucl Med 25 :249-252.
82. Miyauchi, A, Inoue, H, Tomoda, C Amino, N 2009 Evaluation of chemocauterization treatment for obliteration of pyriform sinus fistula as a route of infection causing acute suppurative thyroiditis Thyroid 19 :789-793.
83. Nishihara, E, Ohye, H, Amino, N, Takata, K, Arishima, T, Kudo, T, Ito, M, Kubota, S, Fukata, S Miyauchi, A 2008 Clinical characteristics of 852 patients with subacute thyroiditis before treatment Intern Med 47 :725-729.
84. Miyauchi, A 2010 Thyroid gland: A new management algorithm for acute suppurative thyroiditis? Nat Rev Endocrinol 6 :424-426.
85. Masuoka, H, Miyauchi, A, Tomoda, C, Inoue, H, Takamura, Y, Ito, Y, Kobayashi, K Miya, A 2011 Imaging studies in sixty patients with acute suppurative thyroiditis Thyroid 21 :1075-1080.
86. Ruchala, M, Szczepanek-Parulska, E, Zybek, A, Moczko, J, Czarnywojtek, A, Kaminski, G Sowinski, J 2011 The role of sonoelastography in acute, subacute and chronic thyroiditis – a novel application of the method Eur J Endocrinol.
87. Bernard, PJ, Som, PM, Urken, ML, Lawson, W Biller, HF 1988 The CT findings of acute thyroiditis and acute suppurative thyroiditis Otolaryngol Head Neck Surg 99 :489-493.
88. Yung, G, Kannangara, K, Bui, C, Mansberg, R Champion, B 2010 Riedel thyroiditis demonstrated on gallium scintigraphy Clin Nucl Med 35 :614-617.
89. Park, NH, Park, HJ, Park, CS, Kim, MS Park, SI 2011 The emerging echogenic tract sign of pyriform sinus fistula: an early indicator in the recovery stage of acute suppurative thyroiditis AJNR Am J Neuroradiol 32 :E44-46.
90. Miyauchi, A, Tomoda, C, Uruno, T, Takamura, Y, Ito, Y, Miya, A, Kobayashi, K, Matsuzuka, F, Fukata, S, Amino, N Kuma, K 2005 Computed tomography scan under a trumpet maneuver to demonstrate piriform sinus fistulae in patients with acute suppurative thyroiditis Thyroid 15 :1409-1413.
91. Ukiyama, E, Endo, M, Yoshida, F Watanabe, T 2007 Light guided procedure for congenital pyriform sinus fistula; new and simple procedure for impalpable fistula Pediatr Surg Int 23 :1241-1243.
92. Kim, KH, Sung, MW, Koh, TY, Oh, SH Kim, IS 2000 Pyriform sinus fistula: management with chemocauterization of the internal opening Ann Otol Rhinol Laryngol 109 :452-456.
93. Pereira, KDSmith, SL 2008 Endoscopic chemical cautery of piriform sinus tracts: a safe new technique Int J Pediatr Otorhinolaryngol 72 :185-188.
94. Smith, SLPereira, KD 2008 Suppurative thyroiditis in children: a management algorithm Pediatr Emerg Care 24 :764-767.
95. Jordan, JA, Graves, JE, Manning, SC, McClay, JE Biavati, MJ 1998 Endoscopic cauterization for treatment of fourth branchial cleft sinuses Arch Otolaryngol Head Neck Surg 124 :1021-1024.
96. Rauhofer, U, Prager, G, Hormann, M, Auer, H, Kaserer, K Niederle, B 2003 Cystic echinococcosis of the thyroid gland in children and adults Thyroid 13 :497-502.
97. Mordes, DABrachtel, EF 2011 Cytopathology of subacute thyroiditis Diagn Cytopathol.
98. Nicoucar, K, Giger, R, Jaecklin, T, Pope, HG, Jr. Dulguerov, P 2010 Management of congenital third branchial arch anomalies: a systematic review Otolaryngol Head Neck Surg 142 :21-28 e22.
99. Pereira, KD, Losh, GG, Oliver, D Poole, MD 2004 Management of anomalies of the third and fourth branchial pouches Int J Pediatr Otorhinolaryngol 68 :43-50.
100. Ogawa, E, Katsushima, Y, Fujiwara, I Iinuma, K 2003 Subacute thyroiditis in children: patient report and review of the literature J Pediatr Endocrinol Metab 16 :897-900.
101. Volpe, R 1993 The management of subacute (DeQuervain’s) thyroiditis Thyroid 3 :253-255.
102. Galluzzo, A, Giordano, C, Andronico, F, Filardo, C, Andronico, G Bompiani, G 1980 Leukocyte migration test in subacute thyroiditis: hypothetical role of cell-mediated immunity J Clin Endocrinol Metab 50 :1038-1041.
103. Tamai, H, Nozaki, T, Mukuta, T, Morita, T, Matsubayashi, S, Kuma, K, Kumagai, LF Nagataki, S 1991 The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis J Clin Endocrinol Metab 73 :245-250.
104. Parmar, RC, Bavdekar, SB, Sahu, DR, Warke, S Kamat, JR 2001 Thyroiditis as a presenting feature of mumps Pediatr Infect Dis J 20 :637-638.
105. Dimos, G, Pappas, G Akritidis, N 2010 Subacute thyroiditis in the course of novel H1N1 influenza infection Endocrine 37 :440-441.
106. Volta, C, Carano, N, Street, ME Bernasconi, S 2005 Atypical subacute thyroiditis caused by Epstein-Barr virus infection in a three-year-old girl Thyroid 15 :1189-1191.
107. Satoh, M 1975 Virus-like particles in the follicular epithelium of the thyroid from a patient with subacute thyroiditis (deQuervain’s). Acta Pathol Jpn 25 :499-501.
108. Engkakul, P, Mahachoklertwattana, P Poomthavorn, P 2011 de Quervain thyroiditis in a young boy following hand-foot-mouth disease Eur J Pediatr 170 :527-529.
109. Luotola, K, Hyoty, H, Salmi, J, Miettinen, A, Helin, H Pasternack, A 1998 Evaluation of infectious etiology in subacute thyroiditis–lack of association with coxsackievirus infection APMIS 106 :500-504.
110. Mori, K, Yoshida, K, Funato, T, Ishii, T, Nomura, T, Fukuzawa, H, Sayama, N, Hori, H, Ito, S Sasaki, T 1998 Failure in detection of Epstein-Barr virus and cytomegalovirus in specimen obtained by fine needle aspiration biopsy of thyroid in patients with subacute thyroiditis Tohoku J Exp Med 186 :13-17.
111. Espino Montoro, A, Medina Perez, M, Gonzalez Martin, MC, Asencio Marchante, R Lopez Chozas, JM 2000 [Subacute thyroiditis associated with positive antibodies to the Epstein-Barr virus] An Med Interna 17 :546-548.
112. Al Maawali, A, Al Yaarubi, S Al Futaisi, A 2008 An infant with cytomegalovirus-induced subacute thyroiditis J Pediatr Endocrinol Metab 21 :191-193.
113. Volpe, R, Row, VV Ezrin, C 1967 Circulating viral and thyroid antibodies in subacute thyroiditis J Clin Endocrinol Metab 27 :1275-1284.
114. Desailloud, RHober, D 2009 Viruses and thyroiditis: an update Virol J 6 :5.
115. Buc, M, Nyulassy, S, Hnilica, P Stefanovic, J 1976 HLA-BW35 and subacute de Quervain’s thyroiditis [proceedings] Diabete Metab 2 :163.
116. Hamaguchi, E, Nishimura, Y, Kaneko, S Takamura, T 2005 Subacute thyroiditis developed in identical twins two years apart Endocr J 52 :559-562.
117. Kabalak, TOzgen, AG 2002 Familial occurrence of subacute thyroiditis Endocr J 49 :207-209.
118. Kramer, AB, Roozendaal, C Dullaart, RP 2004 Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35 Thyroid 14 :544-547.
119. Zein, EF, Karaa, SE Megarbane, A 2007 Familial occurrence of painful subacute thyroiditis associated with human leukocyte antigen-B35 Presse Med 36 :808-809.
120. Kalmus, Y, Kovatz, S, Shilo, L, Ganem, G Shenkman, L 2000 Sweet’s syndrome and subacute thyroiditis Postgrad Med J 76 :229-230.
121. Richard, J, Lazarte, S, Calame, A Lingvay, I 2010 Sweet’s syndrome and subacute thyroiditis: an unrecognized association? Thyroid 20 :1425-1426.
122. Vassilopoulou-Sellin, R, Sella, A, Dexeus, FH, Theriault, RL Pololoff, DA 1992 Acute thyroid dysfunction (thyroiditis) after therapy with interleukin-2 Horm Metab Res 24 :434-438.
123. Amenomori, M, Mori, T, Fukuda, Y, Sugawa, H, Nishida, N, Furukawa, M, Kita, R, Sando, T, Komeda, T Nakao, K 1998 Incidence and characteristics of thyroid dysfunction following interferon therapy in patients with chronic hepatitis C Intern Med 37 :246-252.
124. Hernan Martinez, J, Corder, E, Uzcategui, M, Garcia, M, Sostre, S Garcia, A 2011 Subacute thyroiditis and dyserythropoesis after influenza vaccination suggesting immune dysregulation Bol Asoc Med P R 103 :48-52.
125. Hsiao, JY, Hsin, SC, Hsieh, MC, Hsia, PJ Shin, SJ 2006 Subacute thyroiditis following influenza vaccine (Vaxigrip) in a young female Kaohsiung J Med Sci 22 :297-300.
126. Kryczka, W, Brojer, E, Kowalska, A Zarebska-Michaluk, D 2001 Thyroid gland dysfunctions during antiviral therapy of chronic hepatitis C Med Sci Monit 7 Suppl 1 :221-225.
127. Parana, R, Cruz, M, Lyra, L Cruz, T 2000 Subacute thyroiditis during treatment with combination therapy (interferon plus ribavirin) for hepatitis C virus J Viral Hepat 7 :393-395.
128. Omur, O, Daglyoz, G, Akarca, U Ozcan, Z 2003 Subacute thyroiditis during interferon therapy for chronic hepatitis B infection Clin Nucl Med 28 :864-865.
129. Moser, C, Furrer, J Ruggieri, F 2007 [Neck pain and fever after peginterferon alpha-2a] Praxis (Bern 1994) 96 :205-207.
130. Ohta, Y, Ohya, Y, Fujii, K, Tsuchihashi, T, Sato, K, Abe, I Iida, M 2003 Inflammatory diseases associated with Takayasu’s arteritis Angiology 54 :339-344.
131. Obuobie, K, Al-Sabah, A Lazarus, JH 2002 Subacute thyroiditis in an immunosuppressed patient J Endocrinol Invest 25 :169-171.
132. Ozdogu, H, Boga, C, Bolat, F Ertorer, ME 2006 Wegener’s granulomatosis with a possible thyroidal involvement J Natl Med Assoc 98 :956-958.
133. Algun, E, Alici, S, Topal, C, Ugras, S, Erkoc, R, Sakarya, ME Ozbey, N 2003 Coexistence of subacute thyroiditis and renal cell carcinoma: a paraneoplastic syndrome CMAJ 168 :985-986.
134. Calvi, LDaniels, GH 2011 Acute thyrotoxicosis secondary to destructive thyroiditis associated with cardiac catheterization contrast dye Thyroid 21 :443-449.
135. Carneiro, JR, Macedo, RG Da Silveira, VG 2004 Thyrotoxicosis after gastric bypass Obes Surg 14 :699-701.
136. Sanavi, SAfshar, R 2010 Subacute thyroiditis following ginger (Zingiber officinale) consumption Int J Ayurveda Res 1 :47-48.
137. Chang, TC, Lai, SM, Wen, CY Hsiao, YL 2004 Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis Acta Cytol 48 :155-160.
138. Woolner, LB, Mc, CW Beahrs, OH 1957 Granulomatous thyroiditis (De Quervain’s thyroiditis) J Clin Endocrinol Metab 17 :1202-1221.
139. Koga, M, Hiromatsu, Y, Jimi, A, Toda, S, Koike, N Nonaka, K 1999 Immunohistochemical analysis of Bcl-2, Bax, and Bak expression in thyroid glands from patients with subacute thyroiditis J Clin Endocrinol Metab 84 :2221-2225.
140. Toda, S, Nishimura, T, Yamada, S, Koike, N, Yonemitsu, N, Watanabe, K, Matsumura, S, Gartner, R Sugihara, H 1999 Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture J Pathol 188 :415-422.
141. Luotola, K, Mantula, P, Salmi, J, Haapala, AM, Laippala, P Hurme, M 2001 Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis APMIS 109 :454-460.
142. Chen, K, Wei, Y, Sharp, GC Braley-Mullen, H 2007 Decreasing TNF-alpha results in less fibrosis and earlier resolution of granulomatous experimental autoimmune thyroiditis J Leukoc Biol 81 :306-314.
143. Fang, Y, Sharp, GC, Yagita, H Braley-Mullen, H 2008 A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis J Pathol 216 :505-513.
144. Toda, S, Tokuda, Y, Koike, N, Yonemitsu, N, Watanabe, K, Koike, K, Fujitani, N, Hiromatsu, Y Sugihara, H 2000 Growth factor-expressing mast cells accumulate at the thyroid tissue-regenerative site of subacute thyroiditis Thyroid 10 :381-386.
145. Carle, A, Laurberg, P, Pedersen, IB, Knudsen, N, Perrild, H, Ovesen, L, Rasmussen, LB Jorgensen, T 2006 Epidemiology of subtypes of hypothyroidism in Denmark Eur J Endocrinol 154 :21-28.
146. Wasniewska, M, Vigone, MC, Cappa, M, Aversa, T, Rubino, M De Luca, F 2007 Acute suppurative thyroiditis in childhood: relative frequency among thyroid inflammatory diseases* J Endocrinol Invest 30 :346-347.
147. Fatourechi, V, Aniszewski, JP, Fatourechi, GZ, Atkinson, EJ Jacobsen, SJ 2003 Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study J Clin Endocrinol Metab 88 :2100-2105.
148. Qari, FAMaimani, AA 2005 Subacute thyroiditis in Western Saudi Arabia Saudi Med J 26 :630-633.
149. Anastasilakis, AD, Karanicola, V, Kourtis, A, Makras, P, Kampas, L, Gerou, S Giomisi, A 2011 A case report of subacute thyroiditis during pregnancy: difficulties in differential diagnosis and changes in cytokine levels Gynecol Endocrinol 27 :384-390.
150. Hiraiwa, T, Kubota, S, Imagawa, A, Sasaki, I, Ito, M, Miyauchi, A Hanafusa, T 2006 Two cases of subacute thyroiditis presenting in pregnancy J Endocrinol Invest 29 :924-927.
151. Daniels, GH 2001 Atypical subacute thyroiditis: preliminary observations Thyroid 11 :691-695.
152. Dedivitis, RACoelho, LS 2007 Vocal fold paralysis in subacute thyroiditis Braz J Otorhinolaryngol 73 :138.
153. Nakamura, S, Saio, Y Ishimori, M 1998 Recurrent hemithyroiditis: a case report Endocr J 45 :595-600.
154. Sari, O, Erbas, B Erbas, T 2001 Subacute thyroiditis in a single lobe Clin Nucl Med 26 :400-401.
155. Alper, AT, Hasdemir, H, Akyol, A Cakmak, N 2007 Incessant ventricular tachycardia due to subacute thyroiditis Int J Cardiol 116 :e22-24.
156. Sherman, SI, Simonson, L Ladenson, PW 1996 Clinical and socioeconomic predispositions to complicated thyrotoxicosis: a predictable and preventable syndrome? Am J Med 101 :192-198.
157. Swinburne, JLKreisman, SH 2007 A rare case of subacute thyroiditis causing thyroid storm Thyroid 17 :73-76.
158. Kim, HJ, Jung, TS, Hahm, JR, Hwang, SJ, Lee, SM, Jung, JH, Kim, SK Chung, SI 2011 Thyrotoxicosis-induced acute myocardial infarction due to painless thyroiditis Thyroid 21 :1149-1151.
159. Mizokami, T, Okamura, K, Sato, K, Hirata, T, Yamasaki, K Fujishima, M 1998 Localized painful giant-cell thyroiditis without inflammatory signs in a euthyroid patient followed by serial sonography J Clin Ultrasound 26 :329-332.
160. Cunha, BA, Chak, A Strollo, S 2010 Fever of unknown origin (FUO): de Quervain’s subacute thyroiditis with highly elevated ferritin levels mimicking temporal arteritis (TA) Heart Lung 39 :73-77.
161. Benbassat, CA, Olchovsky, D, Tsvetov, G Shimon, I 2007 Subacute thyroiditis: clinical characteristics and treatment outcome in fifty-six consecutive patients diagnosed between 1999 and 2005 J Endocrinol Invest 30 :631-635.
162. Matsumoto, Y, Amino, N, Kubota, S, Ikeda, N, Morita, S, Nishihara, E, Ohye, H, Kudo, T, Ito, M, Fukata, S Miyauchi, A 2008 Serial changes in liver function tests in patients with subacute thyroiditis Thyroid 18 :815-816.
163. Fragu, P, Rougier, P, Schlumberger, M Tubiana, M 1982 Evolution of thyroid 127I stores measured by X-ray fluorescence in subacute thyroiditis J Clin Endocrinol Metab 54 :162-166.
164. Gordin, ALamberg, BA 1973 Serum thyrotrophin response to thyrotrophin releasing hormone and the concentration of free thyroxine in subacute thyroiditis Acta Endocrinol (Copenh) 74 :111-121.
165. Intenzo, CM, Park, CH, Kim, SM, Capuzzi, DM, Cohen, SN Green, P 1993 Clinical, laboratory, and scintigraphic manifestations of subacute and chronic thyroiditis Clin Nucl Med 18 :302-306.
166. Rapoport, B, Block, MB, Hoffer, PB DeGroot, LJ 1973 Depletion of thyroid iodine during subacute thyroiditis J Clin Endocrinol Metab 36 :610-611.
167. Savoie, JC, Massin, JP, Thomopoulos, P Leger, F 1975 Iodine-induced thyrotoxicosis in apparently normal thyroid glands J Clin Endocrinol Metab 41 :685-691.
168. Woolf, PD 1980 Transient painless thyroiditis with hyperthyroidism: a variant of lymphocytic thyroiditis? Endocr Rev 1 :411-420.
169. Pearce, EN, Bogazzi, F, Martino, E, Brogioni, S, Pardini, E, Pellegrini, G, Parkes, AB, Lazarus, JH, Pinchera, A Braverman, LE 2003 The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease Thyroid 13 :643-648.
170. Rao, NL, Shetty, S, Upadhyaya, K, R, MP, Lobo, EC, Kedilaya, HP Prasad, G 2010 Salivary C-Reactive Protein in Hashimoto’s Thyroiditis and Subacute Thyroiditis Int J Inflam 2010 :514659.
171. Fujii, S, Miwa, U, Seta, T, Ohoka, T Mizukami, Y 2003 Subacute thyroiditis with highly positive thyrotropin receptor antibodies and high thyroidal radioactive iodine uptake Intern Med 42 :704-709.
172. Iitaka, M, Momotani, N, Hisaoka, T, Noh, JY, Ishikawa, N, Ishii, J, Katayama, S Ito, K 1998 TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis Clin Endocrinol (Oxf) 48 :445-453.
173. Kamijo, K 2003 TSH-receptor antibody measurement in patients with various thyrotoxicosis and Hashimoto’s thyroiditis: a comparison of two two-step assays, coated plate ELISA using porcine TSH-receptor and coated tube radioassay using human recombinant TSH-receptor Endocr J 50 :113-116.
174. Takasu, N, Kamijo, K, Sato, Y, Yoshimura, H, Nagata, A Ochi, Y 2004 Sensitive thyroid-stimulating antibody assay with high concentrations of polyethylene glycol for the diagnosis of Graves’ disease Clin Exp Pharmacol Physiol 31 :314-319.
175. Hiromatsu, Y, Ishibashi, M, Miyake, I Nonaka, K 1998 Technetium-99m tetrofosmin imaging in patients with subacute thyroiditis Eur J Nucl Med 25 :1448-1452.
176. Hiromatsu, Y, Ishibashi, M, Nishida, H, Kawamura, S, Kaku, H, Baba, K, Kaida, H Miyake, I 2003 Technetium-99 m sestamibi imaging in patients with subacute thyroiditis Endocr J 50 :239-244.
177. Alonso, O, Mut, F, Lago, G, Aznarez, A, Nunez, M, Canepa, J Touya, E 1998 99Tc(m)-MIBI scanning of the thyroid gland in patients with markedly decreased pertechnetate uptake Nucl Med Commun 19 :257-261.
178. Janssen, OE 2011 [Atypical presentation of subacute thyroiditis] Dtsch Med Wochenschr 136 :519-522.
179. Song, YS, Jang, SJ, Chung, JK Lee, DS 2009 F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and Tc-99m pertechnate scan findings of a patient with unilateral subacute thyroiditis Clin Nucl Med 34 :456-458.
180. Kunz, A, Blank, W Braun, B 2005 De Quervain’s subacute thyroiditis — colour Doppler sonography findings Ultraschall Med 26 :102-106.
181. Park, SY, Kim, EK, Kim, MJ, Kim, BM, Oh, KK, Hong, SW Park, CS 2006 Ultrasonographic characteristics of subacute granulomatous thyroiditis Korean J Radiol 7 :229-234.
182. Omori, N, Omori, K Takano, K 2008 Association of the ultrasonographic findings of subacute thyroiditis with thyroid pain and laboratory findings Endocr J 55 :583-588.
183. Nishihara, E, Hirokawa, M, Ohye, H, Ito, M, Kubota, S, Fukata, S, Amino, N Miyauchi, A 2008 Papillary carcinoma obscured by complication with subacute thyroiditis: sequential ultrasonographic and histopathological findings in five cases Thyroid 18 :1221-1225.
184. Tezuka, M, Murata, Y, Ishida, R, Ohashi, I, Hirata, Y Shibuya, H 2003 MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy J Magn Reson Imaging 17 :163-169.
185. Yeo, SH, Lee, SK, Hwang, I Ahn, EJ 2011 Subacute thyroiditis presenting as a focal lesion on [18F] fluorodeoxyglucose whole-body positron-emission tomography/CT AJNR Am J Neuroradiol 32 :E58-60.
186. Shabb, NSSalti, I 2006 Subacute thyroiditis: fine-needle aspiration cytology of 14 cases presenting with thyroid nodules Diagn Cytopathol 34 :18-23.
187. Ito, M, Takamatsu, J, Yoshida, S, Murakami, Y, Sakane, S, Kuma, K Ohsawa, N 1997 Incomplete thyrotroph suppression determined by third generation thyrotropin assay in subacute thyroiditis compared to silent thyroiditis or hyperthyroid Graves’ disease J Clin Endocrinol Metab 82 :616-619.
188. Vierhapper, H, Bieglmayer, C, Nowotny, P Waldhausl, W 1998 Normal serum concentrations of sex hormone binding-globulin in patients with hyperthyroidism due to subacute thyroiditis Thyroid 8 :1107-1111.
189. Nakano, Y, Kurihara, H Sasaki, J 2011 Graves’ disease following subacute thyroiditis Tohoku J Exp Med 225 :301-309.
190. Tesfaye, H, Cimermanova, R, Cholt, M, Sykorova, P, Pechova, M Prusa, R 2009 Subacute thyroiditis confused with dental problem Cas Lek Cesk 148 :438-441.
191. Meller, J, Sahlmann, CO Scheel, AK 2007 18F-FDG PET and PET/CT in fever of unknown origin J Nucl Med 48 :35-45.
192. Yasuda, S, Shohtsu, A, Ide, M, Takagi, S, Takahashi, W, Suzuki, Y Horiuchi, M 1998 Chronic thyroiditis: diffuse uptake of FDG at PET Radiology 207 :775-778.
193. Liel, Y 2007 The survivor: association of an autonomously functioning thyroid nodule and subacute thyroiditis Thyroid 17 :183-184.
194. King, DL, Stack, BC, Jr., Spring, PM, Walker, R Bodenner, DL 2007 Incidence of thyroid carcinoma in fluorodeoxyglucose positron emission tomography-positive thyroid incidentalomas Otolaryngol Head Neck Surg 137 :400-404.
195. Van den Bruel, A, Maes, A, De Potter, T, Mortelmans, L, Drijkoningen, M, Van Damme, B, Delaere, P Bouillon, R 2002 Clinical relevance of thyroid fluorodeoxyglucose-whole body positron emission tomography incidentaloma J Clin Endocrinol Metab 87 :1517-1520.
196. Zacharia, TT, Perumpallichira, JJ, Sindhwani, V Chavhan, G 2002 Gray-scale and color Doppler sonographic findings in a case of subacute granulomatous thyroiditis mimicking thyroid carcinoma J Clin Ultrasound 30 :442-444.
197. Xie, P, Xiao, Y Liu, F 2011 Real-time ultrasound elastography in the diagnosis and differential diagnosis of subacute thyroiditis J Clin Ultrasound 39 :435-440.
198. Martinez, DSChopra, IJ 2003 Use of oral cholecystography agents in the treatment of hyperthyroidism of subacute thyroiditis Panminerva Med 45 :53-57.
199. Mizukoshi, T, Noguchi, S, Murakami, T, Futata, T Yamashita, H 2001 Evaluation of recurrence in 36 subacute thyroiditis patients managed with prednisolone Intern Med 40 :292-295.
200. Duininck, TM, van Heerden, JA, Fatourechi, V, Curlee, KJ, Farley, DR, Thompson, GB, Grant, CS Lloyd, RV 2002 de Quervain’s thyroiditis: surgical experience Endocr Pract 8 :255-258.
201. Nishihara, E, Amino, N, Ohye, H, Ota, H, Ito, M, Kubota, S, Fukata, S Miyauchi, A 2009 Extent of hypoechogenic area in the thyroid is related with thyroid dysfunction after subacute thyroiditis J Endocrinol Invest 32 :33-36.
202. Bogazzi, F, Dell’Unto, E, Tanda, ML, Tomisti, L, Cosci, C, Aghini-Lombardi, F, Sardella, C, Pinchera, A, Bartalena, L Martino, E 2006 Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis J Endocrinol Invest 29 :694-699.
203. Izumi, MLarsen, PR 1978 Correlation of sequential changes in serum thyroglobulin, triiodothyronine, and thyroxine in patients with Graves’ disease and subacute thyroiditis Metabolism 27 :449-460.
204. Goodman, HI 1941 Riedel’s Thyroiditis: a review and report of two cases American Journal of Surgery 54 :472-478.
205. Riedel, BM 1896 Die chronische zur Bildung eisenharter Tumoren fuehrende Entzuendung der Shilddruese. Verh Ges Chir. 25 :101-105.
206. Riedel, BM 1896 Vorstellung eines Kranken mit chronischer Strumitis. Verh Ges Chir. 26 :127-129.
207. Riedel, BM 1910 Ueber Verlauf und Ausgang der chronischer Strumitis. Munch Med Wochenschr 57 :1946-1947.
208. de Lange, WE, Freling, NJ, Molenaar, WM Doorenbos, H 1989 Invasive fibrous thyroiditis (Riedel’s struma): a manifestation of multifocal fibrosclerosis? A case report with review of the literature Q J Med 72 :709-717.
209. Zimmermann-Belsing, TFeldt-Rasmussen, U 1994 Riedel’s thyroiditis: an autoimmune or primary fibrotic disease? J Intern Med 235 :271-274.
210. Hay, ID 1985 Thyroiditis: a clinical update Mayo Clin Proc 60 :836-843.
211. Guimaraes, VC, Subacute and Reidel’s Thyroiditis , in Endocrinology: Adult and Pediatric , JL JamesonLJ De Groot, Editors. 2010, Elsevier: Philadelphia. p. 1600-1603.
212. Fatourechi, MM, Hay, ID, McIver, B, Sebo, TJ Fatourechi, V 2011 Invasive fibrous thyroiditis (riedel thyroiditis): the mayo clinic experience, 1976-2008 Thyroid 21 :765-772.
213. Hennessey, JV 2011 Clinical review: Riedel’s thyroiditis: a clinical review J Clin Endocrinol Metab 96 :3031-3041.
214. Balach, ZWLiVolsi, VA, Pathology , in Werner & Ingbar’s The Thyroid; A Fundamental and Clinical Text , LE BravermanRE Utiger, Editors. 2005, Lippincott Williams & Wilkins: Philadelphia. p. 427.
215. Lee, SLAnanthakrishnan, S 2011 Infiltartive thyroid disease , in UpToDate , BD RoseJE Mulder, Editors. BDR, Inc.: Wellesley, MA. p. 1-21.
216. Heufelder, AE, Goellner, JR, Bahn, RS, Gleich, GJ Hay, ID 1996 Tissue eosinophilia and eosinophil degranulation in Riedel’s invasive fibrous thyroiditis J Clin Endocrinol Metab 81 :977-984.
217. Beahrs, OH, McConahey, WM Woolner, LB 1957 Invasive fibrous thyroiditis (Riedel’s struma) J Clin Endocrinol Metab 17 :201-220.
218. Schwaegerle, SM, Bauer, TW Esselstyn, CB, Jr. 1988 Riedel’s thyroiditis Am J Clin Pathol 90 :715-722.
219. Volpe, R, Subacute and Sclerosing Thyroiditis , in Endocrinology , LJ De Groot, Editor. 1995, WB Saunders: Philadelphia. p. 742-751.
220. Torres-Montaner, A, Beltran, M, Romero de la Osa, A Oliva, H 2001 Sarcoma of the thyroid region mimicking Riedel’s thyroiditis J Clin Pathol 54 :570-572.
221. Wan, SK, Chan, JK Tang, SK 1996 Paucicellular variant of anaplastic thyroid carcinoma. A mimic of Reidel’s thyroiditis Am J Clin Pathol 105 :388-393.
222. Katsikas, D, Shorthouse, AJ Taylor, S 1976 Riedel’s thyroiditis Br J Surg 63 :929-931.
223. Cho, MH, Kim, CS, Park, JS, Kang, ES, Ahn, CW, Cha, BS, Lim, SK, Kim, KR Lee, HC 2007 Riedel’s thyroiditis in a patient with recurrent subacute thyroiditis: a case report and review of the literature Endocr J 54 :559-562.
224. LiVolsi, VALoGerfo, P, eds. Thyroiditis . 1981, CRC Press: Boca Raton. 21-42.
225. Pirola, I, Morassi, ML, Braga, M, De Martino, E, Gandossi, E Cappelli, C 2009 A Case of Concurrent Riedel’s, Hashimoto’s and Acute Suppurative Thyroiditis Case Report Med 2009 :535974.
226. McIver, B, Fatourechi, MM, Hay, ID Fatourechi, V 2010 Graves’ disease after unilateral Riedel’s thyroiditis J Clin Endocrinol Metab 95 :2525-2526.
227. Kojima, M, Nakamura, S, Yamane, Y, Shimizu, K, Sugiharal, S Masawa, N 2003 Riedel’s thyroiditis containing cytologically atypically appearing B-cells: a case report Pathol Res Pract 199 :497-501.
228. Chen, K, Wei, Y, Sharp, GC Braley-Mullen, H 2000 Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis J Leukoc Biol 68 :828-835.
229. Dahlgren, M, Khosroshahi, A, Nielsen, GP, Deshpande, V Stone, JH 2010 Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum Arthritis Care Res (Hoboken) 62 :1312-1318.
230. Li, Y, Bai, Y, Liu, Z, Ozaki, T, Taniguchi, E, Mori, I, Nagayama, K, Nakamura, H Kakudo, K 2009 Immunohistochemistry of IgG4 can help subclassify Hashimoto’s autoimmune thyroiditis Pathol Int 59 :636-641.
231. Neild, GH, Rodriguez-Justo, M, Wall, C Connolly, JO 2006 Hyper-IgG4 disease: report and characterisation of a new disease BMC Med 4 :23.
232. Yamamoto, M, Takahashi, H Shinomura, Y 2010 [IgG4-related systemic disease/systemic IgG4-related disease] Rinsho Byori 58 :454-465.
233. Pearce, EN, Farwell, AP Braverman, LE 2003 Thyroiditis N Engl J Med 348 :2646-2655.
234. Annaert, M, Thijs, M, Sciot, R Decallonne, B 2007 Riedel’s thyroiditis occurring in a multinodular goiter, mimicking thyroid cancer J Clin Endocrinol Metab 92 :2005-2006.
235. Lu, L, Gu, F, Dai, WX, Li, WY, Chen, J, Xiao, Y Zeng, ZP 2010 Clinical and pathological features of Riedel’s thyroiditis Chin Med Sci J 25 :129-134.
236. Vigouroux, C, Escourolle, H, Mosnier-Pudar, H, Thomopoulos, P, Louvel, A, Chapuis, Y, Varet, B Luton, JP 1996 [Riedel’s thyroiditis and lymphoma. Diagnostic difficulties] Presse Med 25 :28-30.
237. Sheu, SYSchmid, KW 2003 [Inflammatory diseases of the thyroid gland. Epidemiology, symptoms and morphology] Pathologe 24 :339-347.
238. Shahi, N, Abdelhamid, MF, Jindall, M Awad, RW 2010 Riedel’s thyroiditis masquerading as anaplastic thyroid carcinoma: a case report J Med Case Reports 4 :15.
239. Best, TB, Munro, RE, Burwell, S Volpe, R 1991 Riedel’s thyroiditis associated with Hashimoto’s thyroiditis, hypoparathyroidism, and retroperitoneal fibrosis J Endocrinol Invest 14 :767-772.
240. Chopra, D, Wool, MS, Crosson, A Sawin, CT 1978 Riedel’s struma associated with subacute thyroiditis, hypothyroidism, and hypoparathyroidism J Clin Endocrinol Metab 46 :869-871.
241. Marin, F, Araujo, R, Paramo, C, Lucas, T Salto, L 1989 Riedel’s thyroiditis associated with hypothyroidism and hypoparathyroidism Postgrad Med J 65 :381-383.
242. Nazal, EM, Belmatoug, N, de Roquancourt, A, Lefort, A Fantin, B 2003 Hypoparathyroidism preceding Riedel’s thyroiditis Eur J Intern Med 14 :202-204.
243. Yasmeen, T, Khan, S, Patel, SG, Reeves, WA, Gonsch, FA, de Bustros, A Kaplan, EL 2002 Clinical case seminar: Riedel’s thyroiditis: report of a case complicated by spontaneous hypoparathyroidism, recurrent laryngeal nerve injury, and Horner’s syndrome J Clin Endocrinol Metab 87 :3543-3547.
244. Heufelder, AEBahn, RS 1994 Modulation of Graves’ orbital fibroblast proliferation by cytokines and glucocorticoid receptor agonists Invest Ophthalmol Vis Sci 35 :120-127.
245. Heufelder, AEHay, ID 1995 Further evidence for autoimmune mechanisms in the pathogenesis of Riedel’s invasive fibrous thyroiditis J Intern Med 238 :85-86.
246. Khan, MA, Hashmi, SM, Prinsley, PR Premachandra, DJ 2004 Reidel’s thyroiditis and Tolosa-Hunt syndrome, a rare association J Laryngol Otol 118 :159-161.
247. Geissler, B, Wagner, T, Dorn, R Lindemann, F 2001 Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis J Endocrinol Invest 24 :111-115.
248. Meijer, S, Hoitsma, HF Scholtmeijer, R 1976 Idiopathic retroperitoneal fibrosis in multifocal fibrosclerosis Eur Urol 2 :258-260.
249. Meyer, SHausman, R 1976 Occlusive phlebitis in multifocal fibrosclerosis Am J Clin Pathol 65 :274-283.
250. Vaidya, B, Coulthard, A, Goonetilleke, A, Burn, DJ, James, RA Kendall-Taylor, P 1998 Cerebral venous sinus thrombosis: a late sequel of invasive fibrous thyroiditis Thyroid 8 :787-790.
251. Natt, N, Heufelder, AE, Hay, ID, Grant, CS Goellner, JR 1997 Extracervical fibrosclerosis causing obstruction of a ventriculo-peritoneal shunt in a patient with hydrocephalus and invasive fibrous thyroiditis (Riedel’s struma) Clin Endocrinol (Oxf) 47 :107-111.
252. Egsgaard Nielsen, V, Hecht, P, Krogdahl, AS, Andersen, PB Hegedus, L 2003 A rare case of orbital involvement in Riedel’s thyroiditis J Endocrinol Invest 26 :1032-1036.
253. Hines, RC, Scheuermann, HA, Royster, HP Rose, E 1970 Invasive fibrous (Riedel’s) thyroiditis with bilateral fibrous parotitis JAMA 213 :869-871.
254. Julie, C, Vieillefond, A, Desligneres, S, Schaison, G, Grunfeld, JP Franc, B 1997 Hashimoto’s thyroiditis associated with Riedel’s thyroiditis and retroperitoneal fibrosis Pathol Res Pract 193 :573-577; discussion 578.
255. Rao, CR, Ferguson, GC Kyle, VN 1973 Retroperitoneal fibrosis associated with Riedel’s struma Can Med Assoc J 108 :1019-1021.
256. Brihaye, B, Lidove, O, Sacre, K, Laissy, JP, Escoubet, B, Valla, D Papo, T 2008 Diffuse periarterial involvement in systemic fibrosclerosis with Riedel’s thyroiditis, sclerosing cholangitis, and retroperitoneal fibrosis Scand J Rheumatol 37 :490-492.
257. Hamed, G, Tsushima, K, Yasuo, M, Kubo, K, Yamazaki, S, Kawa, S, Hamano, H Yamamoto, H 2007 Inflammatory lesions of the lung, submandibular gland, bile duct and prostate in a patient with IgG4-associated multifocal systemic fibrosclerosis Respirology 12 :455-457.
258. Owen, K, Lane, H Jones, MK 2001 Multifocal fibrosclerosis: a case of thyroiditis and bilateral lacrimal gland involvement Thyroid 11 :1187-1190.
259. Cooper, DS, Doherty, GM, Haugen, BR, Kloos, RT, Lee, SL, Mandel, SJ, Mazzaferri, EL, McIver, B, Pacini, F, Schlumberger, M, Sherman, SI, Steward, DL Tuttle, RM 2009 Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer Thyroid 19 :1167-1214.
260. Ozgen, ACila, A 2000 Riedel’s thyroiditis in multifocal fibrosclerosis: CT and MR imaging findings AJNR Am J Neuroradiol 21 :320-321.
261. Papi, G, Corrado, S, Cesinaro, AM, Novelli, L, Smerieri, A Carapezzi, C 2002 Riedel’s thyroiditis: clinical, pathological and imaging features Int J Clin Pract 56 :65-67.
262. Slman, R, Monpeyssen, H, Desarnaud, S, Haroche, J, Fediaevsky, LD, Fabrice, M, Seret-Begue, D, Amoura, Z, Aurengo, A Leenhardt, L 2011 Ultrasound, Elastography, and Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging in Riedel’s Thyroiditis: Report of Two Cases Thyroid.
263. Harigopal, M, Sahoo, S, Recant, WM DeMay, RM 2004 Fine-needle aspiration of Riedel’s disease: report of a case and review of the literature Diagn Cytopathol 30 :193-197.
264. Perez Fontan, PJ, Cordido Carbillido, F, Pompo Felipe, F, Mosquera Oses, J Villalba Martin, C 1993 Riedel thyroiditis: US, CT, and MR evaluation J Comput Assist Tomogr. 17 :324-325.
265. Lo, JC, Loh, KC, Rubin, AL, Cha, I Greenspan, FS 1998 Riedel’s thyroiditis presenting with hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine therapy Clin Endocrinol (Oxf) 48 :815-818.
266. Takahashi, N, Okamoto, K, Sakai, K, Kawana, M Shimada-Hiratsuka, M 2002 MR findings with dynamic evaluation in Riedel’s thyroiditis Clin Imaging 26 :89-91.
267. Drieskens, O, Blockmans, D, Van den Bruel, A Mortelmans, L 2002 Riedel’s thyroiditis and retroperitoneal fibrosis in multifocal fibrosclerosis: positron emission tomographic findings Clin Nucl Med 27 :413-415.
268. Kotilainen, P, Airas, L, Kojo, T, Kurki, T, Kataja, K, Minn, H Nuutila, P 2004 Positron emission tomography as an aid in the diagnosis and follow-up of Riedel’s thyroiditis Eur J Intern Med 15 :186-189.
269. Moulik, PK, Al-Jafari, MS Khaleeli, AA 2004 Steroid responsiveness in a case of Riedel’s thyroiditis and retroperitoneal fibrosis Int J Clin Pract 58 :312-315.
270. Papi, GLiVolsi, VA 2004 Current concepts on Riedel thyroiditis Am J Clin Pathol 121 Suppl :S50-63.
271. Bagnasco, M, Passalacqua, G, Pronzato, C, Albano, M, Torre, G Scordamaglia, A 1995 Fibrous invasive (Riedel’s) thyroiditis with critical response to steroid treatment J Endocrinol Invest 18 :305-307.
272. Hostalet, F, Hellin, D Ruiz, JA 2003 Tumefactive fibroinflammatory lesion of the head and neck treated with steroids: a case report Eur Arch Otorhinolaryngol 260 :229-231.
273. Rodriguez, I, Ayala, E, Caballero, C, De Miguel, C, Matias-Guiu, X, Cubilla, AL Rosai, J 2001 Solitary fibrous tumor of the thyroid gland: report of seven cases Am J Surg Pathol 25 :1424-1428.
274. Thomson, JA, Jackson, IM Duguid, WP 1968 The effect of steroid therapy on Riedel’s thyroiditis Scott Med J 13 :13-16.
275. Tutuncu, NB, Erbas, T, Bayraktar, M Gedik, O 2000 Multifocal idiopathic fibrosclerosis manifesting with Riedel’s thyroiditis Endocr Pract 6 :447-449.
276. Vaidya, B, Harris, PE, Barrett, P Kendall-Taylor, P 1997 Corticosteroid therapy in Riedel’s thyroiditis Postgrad Med J 73 :817-819.
277. Few, J, Thompson, NW, Angelos, P, Simeone, D, Giordano, T Reeve, T 1996 Riedel’s thyroiditis: treatment with tamoxifen Surgery 120 :993-998; discussion 998-999.
278. Levy, JM, Hasney, CP, Friedlander, PL, Kandil, E, Occhipinti, EA Kahn, MJ 2010 Combined mycophenolate mofetil and prednisone therapy in tamoxifen- and prednisone-resistant Reidel’s thyroiditis Thyroid 20 :105-107.
279. Clark, CP, Vanderpool, D Preskitt, JT 1991 The response of retroperitoneal fibrosis to tamoxifen Surgery 109 :502-506.
280. Dabelic, N, Jukic, T, Labar, Z, Novosel, SA, Matesa, N Kusic, Z 2003 Riedel’s thyroiditis treated with tamoxifen Croat Med J 44 :239-241.
281. De, M, Jaap, A Dempster, J 2002 Tamoxifen therapy in steroid-resistant Riedels disease Scott Med J 47 :12-13.
282. Erdogan, MF, Anil, C, Turkcapar, N, Ozkaramanli, D, Sak, SD Erdogan, G 2009 A case of Riedel’s thyroiditis with pleural and pericardial effusions Endocrine 35 :297-301.
283. Jung, YJ, Schaub, CR, Rhodes, R, Rich, FA Muehlenbein, SJ 2004 A case of Riedel’s thyroiditis treated with tamoxifen: another successful outcome Endocr Pract 10 :483-486.
284. Pritchyk, K, Newkirk, K, Garlich, P Deeb, Z 2004 Tamoxifen therapy for Riedel’s thyroiditis Laryngoscope 114 :1758-1760.
285. Arteaga, CL, Tandon, AK, Von Hoff, DD Osborne, CK 1988 Transforming growth factor beta: potential autocrine growth inhibitor of estrogen receptor-negative human breast cancer cells Cancer Res 48 :3898-3904.
286. Butta, A, MacLennan, K, Flanders, KC, Sacks, NP, Smith, I, McKinna, A, Dowsett, M, Wakefield, LM, Sporn, MB, Baum, M et al. 1992 Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment Cancer Res 52 :4261-4264.
287. Colletta, AA, Wakefield, LM, Howell, FV, van Roozendaal, KE, Danielpour, D, Ebbs, SR, Sporn, MB Baum, M 1990 Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts Br J Cancer 62 :405-409.
288. Hoang, TD, Mai, VQ, Clyde, PW, Glister, BC Shakir, MK 2011 Multinodular goiter as the initial presentation of systemic sarcoidosis: limitation of fine-needle biopsy Respir Care 56 :1029-1032.
289. Anolik, RB, Schaffer, A, Kim, EJ Rosenbach, M 2012 Thyroid dysfunction and cutaneous sarcoidosis J Am Acad Dermatol 66 :167-168.
290. Vailati, A, Marena, C, Aristia, L, Sozze, E, Barosi, G, Inglese, V, Luisetti, M Bossolo, PA 1993 Sarcoidosis of the thyroid: report of a case and a review of the literature Sarcoidosis 10 :66-68.
291. Ozdemir, D, Dagdelen, S Erbas, T 2010 Endocrine involvement in systemic amyloidosis Endocr Pract 16 :1056-1063.
292. Kazdaghli Lagha, E, M’Sakni, I, Bougrine, F, Laabidi, B, Ben Ghachem, D Bouziani, A 2010 Amyloid goiter: first manifestation of systemic amyloidosis Eur Ann Otorhinolaryngol Head Neck Dis 127 :108-110.
293. Ozdemir, D, Dagdelen, S, Erbas, T, Sokmensuer, C, Erbas, B Cila, A 2011 Amyloid goiter and hypopituitarism in a patient with systemic amyloidosis Amyloid 18 :32-34.
294. Sethi, Y, Gulati, A, Singh, I, Rao, S Singh, N 2011 Amyloid goiter: a case of primary thyroid amyloid disease Laryngoscope 121 :961-964.
295. Vanguri, VKNose, V 2008 Transthyretin amyloid goiter in a renal allograft recipient Endocr Pathol 19 :66-73.
296. Hamed, G, Heffess, CS, Shmookler, BM Wenig, BM 1995 Amyloid goiter. A clinicopathologic study of 14 cases and review of the literature Am J Clin Pathol 104 :306-312.
297. Coca-Pelaz, A, Vivanco-Allende, B, Alvarez-Marcos, C Suarez-Nieto, C 2011 Multifocal papillary thyroid carcinoma associated with primary amyloid goiter Auris Nasus Larynx.
298. Coli, A, Bigotti, G, Zucchetti, F, Negro, F Massi, G 2000 Papillary carcinoma in amyloid goitre J Exp Clin Cancer Res 19 :391-394.
299. Nessim, STamilia, M 2005 Papillary thyroid carcinoma associated with amyloid goiter Thyroid 15 :382-385.
300. Ozdemir, BH, Akman, B Ozdemir, FN 2001 Amyloid goiter in Familial Mediterranean Fever (FMF): a clinicopathologic study of 10 cases Ren Fail 23 :659-667.
301. Bando, Y, Ushiogi, Y, Toya, D, Tanaka, N Fujisawa, M 2001 Painless thyroiditis associated with severe inflammatory reactions in amyloid goiter: a case report Endocr J 48 :323-329.
302. Bryer-Ash, M, Lodhi, W, Robbins, K Morrison, R 2001 Early thyrotoxic thyroiditis after radiotherapy for tonsillar carcinoma Arch Otolaryngol Head Neck Surg 127 :209-211.
303. Blenke, EJ, Vernham, GA Ellis, G 2004 Surgery-induced thyroiditis following laryngectomy J Laryngol Otol 118 :313-314.
304. Espiritu, RPDean, DS 2010 Parathyroidectomy-induced thyroiditis Endocr Pract 16 :656-659.
305. McDermott, A, Onyeaka, CV Macnamara, M 2002 Surgery-induced thyroiditis: fact or fiction? Ear Nose Throat J 81 :408-410.
1. Hedinger, C, Dillwyn Williams, E, Sobin, L 1989. The WHO histological classification of thyroid tumors. A commentary on the second edition. Cancer 63:908-911
2.Namba, H, Matsuo, K, Fagin, J 1990 Clonal composition of benign and malignant human thyroid tumors. J Clin In 86:.
3.. Parma, J, Duprez, L, Van Sande, J, et al. 1993. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649-651
4.. Tonacchera, M, Chiovato, L, Pinchera, A, et al. 1998 Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab 83:492-8
5. Coclet, J, Foureau, F, Ketelbant, P, Galand, P, Dumont, J 1989. Cell population kinetics in dog and human adult thyroid. Clinical Endocrinol 31:655-665
6. Viglietto, G, Chiappetta, G, Martinez-Tello, F J, et al. 1995 RET/PTC oncogene activation is an early event in thyroid carcinogenesis. Oncogene 11:1207-10
7. Hamburger, J I 1980; Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab 50:1089-1093
8. Silverstein, G, Burke, G, Cogan, R 1967. The natural history of the auto-nomous hyperfunctioning thyroid nodule. Ann Intern Med 67:539
9. Evered, D, Clark, F, Peterson, V 1974. Thyroid function in euthyroid subjects with autonomous thyroid nodules. Clin Endocrinol 3:149
10. Horst, W, Rosler, H, Schneider, C, Labhart, A 1967. 306 cases of toxic adenoma. Clinical aspects; findings in radioiodine diagnostics; radiochromatography and histology; results of 131I and surgical treatment. J Nucl Med 8:515
11.Parma, J, Duprez, L, Van Sande, J, et al. 1993. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649-651
12.Suarez, H, du Villard, J, Caillou, B, Schlumberger, M, Parmentier, C, Monier, M 1991. Gsp mutations in human thyroid tumors. Oncogene 6:677-679
13. see 10
13a. DeGroot, L 1970. Lack of iodide trapping in “cold” thyroid nodules. Acta Endocrinol Panam 1:27
14. Field, J, Larsen, P, Yamashita, K, Mashiter, K, Dekke, A 1973. Demonstration of iodide transport defect but normal iodide organification in nonfunctioning nodules of human thyroid glands. J Clin Invest 52:2404
15. Fragu, P, Nataf, B 1977. Human thyroid peroxidase activity in benign and malign thyroid disorders. J Clin Endocrinol Metab 45:1089
16. Demeester-Mirkine, N, Van Sande, J, Corvilain, H, Dumont, J 1975. Benign thyroid nodule with normal iodide trap and defective organification. J Clin Endocrinol Metab 41:1169
17. Burke, G, Szabo, M 1972. Dissociation of in vivo and in vitro “autonomy” in hyperfunctioning thyroid nodules. J Clin Endocrinol Metab 35:199
18. Sande Van, J, Mockel, J, Boeynaems, J, Dor, P, Andry, G, Dumont, J 1980. Regulation of cyclic nucleotide and prostaglandin formation in normal human thyroid tissue and in autonomous nodules. J Clin Endocrinol Metab 50:776
19. Smanik, P, Ryu, K-Y, Thel, K, Mazzaferri, E, Jhiang, S 1997. Expression; exon-intron organization; and chromosome mapping of the human sodium iodide symporter. Endocrinology 138:3555-8
20.Arturi, F, Russo, D, Schlumberger, M, et al. 1998. Iodine symporter gene expression in human thyroid tumors. J Clin Endocrinol Metab 83:2493-96
21. Thomas, C J, Buckwalter, J, Staab, E, Kerr, C 1976. Evaluation of dominant thyroid masses. Ann Surg 183:464
22. Sipple, J H 1984 Multiple endocrine neoplasia type 2 syndromes: historical perspectives. Henry Ford Hosp Med J 32:219-21
23.Schimke, R, Hartmann, W, Prout, T, Rimoin, D 1968. Syndrome of bilateral pheochromocytoma; medullary thyroid carcinoma; and multiple neuromas. N Engl J Med 279:1
24.Sapira, J, Altman, M, Vandyk, K, Shapiro, A 1965. Bilateral adrenal pheo-chromocytoma and medullary thyroid carcinoma. N Engl J Med 273:140
25. Duffy, B J, Fitzgerald, P 1950. Cancer of the thyroid in children. A report of twenty-eight cases. J Clin Endocrinol 10:1296
26. Clark, D 1955. Association of irradiation with cancer of the thyroid in children and adolescents. JAMA 159:1007
27. Modan, B, Ron, E, Werner, A 1977. Thyroid cancer following scalp irradiation. Therapeutic Radiology 123:741
28 DeGroot, L, Frohman, L, Kaplan, E, Refetoff, S e 1977. Radiation-Associated Thyroid Carcinoma. New York Grune & Stratton:539 pages
29. Refetoff, S, Harrison, J, Karanfilski, B, Kaplan, E, DeGroot, L, Bekerman, C 1975. Continuing occurrence of thyroid carcinoma after irradiation to the neck in infancy and childhood. N Engl J Med 292:171
30 DeGroot, L, Paloyan, E 1973. Thyroid carcinoma and radiation. A Chicago endemic. JAMA 225:487
31. Sokal, J 1959. The problem of malignancy in nodular goiter — recapitulation and a challenge. JAMA 170:61
32. Veith, F, Brooks, J, Grigsby, W, Selenkow, H 1964. The nodular thyroid gland and cancer. N Engl J Med 270:431
32.1 Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, Orcutt J, Moore FD Jr, Larsen PR, Marqusee E, Alexander EK. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006 Sep;91(9):3411-7.
33. Hoffman, G, Thompson, N, Heffron, C 1972. The solitary thyroid nodule. Arch Surg 105:379
33.1 Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, Chen H. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab. 2008 Mar;93(3):809-14.
34. Pacini, F, Fontanelli, M, Fugazzola, L, et al. 1994. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosisof unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Mertab 78:826-9
35. Rieu, M, Lame, M, Richard, A, et al. 1995. Prevalence of sporadic medullary thyroid carcinoma. the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. Clin Endocrinol (Oxf) 42:453-7
36. Niccoli, P, Wion-Barbot, N, Caron, P, et al. 1997. Interest of routine measurement of serum calcitonin. Study in a large series of thyroidectomized patients. J Clin Endocrinol Metab 82:338-341
37. Gagel, R 1997. The goitrous patient with an elevated serum calcitonin — what to do? J Clin Endocrinol Metab 82:335
37.0. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 19:1167-214, 2009.
38. Hamlin, E, Vickery, A 1956. Needle biopsy of the thyroid gland. N Engl J Med 254:742
39. Walfish, P, Hazani, E, Strawbridge, H, Miskin, M, Rosen, B 1977. Combined ultrasound and needle aspiration cytology in the assessment and management of hypofunctioning thyroid nodule. Ann Intern Med 87:270
40. Gershengorn, M, McClung, M, Chu, W, Hanson, T, Weintraub, B, Robbins, J 1977. Fine-needle aspiration cytology in the preoperative diagnosis of thyroid nodules. Ann Intern Med 87:265
41.Baloch, Z, Sack, M, Livolsi, V, Gupta, P 1998. Fine-needle aspiration of thyroid. an institutional experience. Thyroid 8:565-9
42. Benvenga, S, Bartolone, L, Squadrito, S, Trimarchi, F 1997. Thyroid hormone autoantibodies elicited by diagnostic fine needle biopsy. J Clin Endocrinol Metab 82:4217-4223
43 Wilems, J-S, Lowhagen, T 1981. Fine needle aspiration cytology in thyroid disease. . Clin Endocrinol Metab 2:247
44 Gharib, H, Goellner, J, Johnson, D 1993. Fine needle aspiration cytology of the thyroid. A 12-year experience with 11;000 biopsies. Clin Lab Med 13:699-709
44.1 Tee YY, Lowe AJ, Brand CA, Judson RT. Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review. Ann Surg. 2007 Nov;246(5):714-20.
45. Pacini, F, Fugazzola, L, Lippi, F, et al. 1992 Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses. a clue to the diagnosis of metastatic thyroid cancer. J Clin Endocrinol Metab 74:1401-4
46. Chow, L S, Gharib, H, Goellner, J R, van Heerden, J A 2001 Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Thyroid 11:1147-51
47. Khurana, K, Richards, V, Chopra, P, Izquierdo, R, Rubens, D, Mesonero, C 1998. The role of ultrasonography-guided fine-needle aspiration biopsy in the management of nonpalpable and palpable thyroid nodules. Thyroid 8:511
48. Erdogan, M, Kamel, N, Aras, D, Akdogan, A, Baskal, N, Erdogan, G 1998. Value of reaspirations in benign nodular thyroid disease. Thyroid 8:1087
49. Bieche, I, Ruffet, E, Zweibaum, A, Vilde, F, Lidereau, R, Franc, B 1997. MUC1 Mucin gene; transcripts; and protein in adenomas and papillary carcinomas of the thyroid. Thyroid 7:725
50 Brousset, P, Chaouche, N, Leprat, F, et al. 1997. Telomerase activity in human thyroid carcinomas originating from the follicular cells. J Clin Endocrinol Metab 82:4214-4216
51 Khoo, M L, Beasley, N J, Ezzat, S, Freeman, J L, Asa, S L 2002 Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma. J Clin Endocrinol Metab 87:1814-8
51.1 Ferraz C , Eszlinger M , Paschke R . Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab. 2011 Jul;96(7):2016-26).
51.2 Nikiforov YE , Ohori NP, Hodak SP , Carty SE, Lebeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of Mutational Testing on the Diagnosis and Management of Patients with Cytologically Indeterminate Thyroid Nodules: A Prospective Analysis of 1056 FNA Samples. J Clin Endocrinol Metab . 2011 Nov;96(11):3390-7.
51.3. Silvia Cantara, Marco Capezzone, Stefania Marchisotta, Serena Capuano, Giulia Busonero, Paolo Toti, Andrea Di Santo, Giuseppe Caruso, Anton Ferdinando Carli, Lucia Brilli, Annalisa Montanaro, and Furio Pacini. Impact of Proto-Oncogene Mutation Detection in Cytological Specimens from Thyroid Nodules Improves the Diagnostic Accuracy of Cytology. J Clin Endocrinol Metab. 95:1365-69, 2010
51a. Maruta, J; Hashimoto, H; Yamashita, H; Yamashita, H; Noguchi, S. Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological samples for differentiating follicular thyroid carcinoma from follicular adenoma. Arch Surg 139 83-88 2004.
51b. Durand S, Ferraro-Peyret C, Selmi-Ruby S, Paulin C, El Atifi M, Berger F, Berger-Dutrieux N, Decaussin M, Peix JL, Bournaud C, Orgiazzi J, Borson-Chazot F, Rousset B Evaluation of gene expression profiles in thyroid nodule biopsy material to diagnose thyroid cancer. J Clin Endocrinol Metab. 2008 Apr;93(4):1195-202.
51c Shibru D, Hwang J, Khanafshar E, Duh QY, Clark OH, Kebebew E. Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms? Cancer. 2008 Sep 1;113(5):930-5.
52 Clark, O, Okerlund, M, Cavalieri, R, Greenspan, F 1979. Diagnosis and treatment of thyroid; parathyroid; and thyroglossal duct cysts. J Clin Endocrinol Metab 48:983
52.1 Leboulleux S , Girard E , Rose M , Travagli JP , Sabbah N , Caillou B , Hartl DM , Lassau N , Baudin E , Schlumberger M Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab. 2007 Sep;92(9):3590-4
53. Marcocci, C, Vitti, P, Cetani, F, Catalano, F, Concetti, R, Pinchera, A 1991. Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 72:209-13.
53.1 Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology. 2010 RagoT, ScutariM, SantiniF, LoiaconoV, PiaggiP, DiCoscio G,Basolo F,Berti P,Pinchera A, Vitti P .J ClinEndocrinol Metab.95:5274-80.
53.2 Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. 2007 Rago T, Santini F, Scutari M, Pinchera A, Vitti P . J Clin Endocrinol Metab. 92:2917-22.
54. Kendall, L, Condon, R 1969. Prediction of malignancy in solitary thyroid nodules. Lancet 1:1071
55. Miller, J, Hamburger, J 1965.. The thyroid scintigram. 1. The hot nodule. Radiology 84:66
56. Attie, J 1960. The use of radioactive iodine in the evaluation of thyroid nodules. Surgery 47:611
57. Dische, S 1964. The radioisotope scan applied to the detection of carcinoma in thyroid swellings. Cancer 17:473
58. Fujimoto, Y, Oka, A, Nagataki, S 1972. Occurrence of papillary carcinoma in hyperfunctioning thyroid nodule. Report of a case. Endocrinol Jpn 19:371
59. Scott, M, Crawford, J 1976. Solitary thyroid nodules in childhood. Is the incidence of thyroid carcinoma declining? Pediatrics 58:521
60.Messaris, G, Evangelou, G, Tountas, C 1973. Incidence of carcinoma in cold nodules of the thyroid gland. Surgery 74:447
61. Van den Bruel, A, Maes, A, De Potter, T, et al. 2002 Clinical relevance of thyroid fluorodeoxyglucose-whole body positron emission tomography incidentaloma. J Clin Endocrinol Metab 87:1517-20
62. Hakama, M Berlin; Springer-Verlag Different world thyroid cancer rates; in Hedinger CE (ed). Thyroid Cancer. International Union Against Cancer Monograph Series:Vol 12.
63. Young, J J, Percy, C, Asire, A e 1082 pages Surveillance; Epidemiology; and End Results. Incidence and Mortality Data; 1973-77. National Cancer Institute Monograph 57 NIH Publication No. 81:2330
64. Goldstein, R, Hart, I 1983. Follow-up of solitary autonomous thyroid nodules treated with 131I. New Engl J Med 309:1473
65. Gorman, C, Robertson, J 1978. Radiation dose in the selection of 131I or surgical treatment for toxic thyroid adenoma. Ann Intern Med 89:85
66. Paracchi, A, Ferrari, C, Livraghi, T, et al. 1992. Percutaneous intranodular ethanol injection. A new treatment for autonomous thyroid adenoma. J Endocrinol Invest 15:353-362
67. Lippi, F, Ferrari, C, Manetti, L, et al. 1996. Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection. results of an Italian multicenter study. The Multicenter Study Group. J Clin Endocrinol Metab 81:3261-3264
68. Monzani, F, Caraccio, N, Goletti, O, et al. S54-8 Treatment of hyperfunctioning thyroid nodules with percutaneous ethanol injection. Eight years’ experience. Exp Clin Endocrinol Diabetes 106: Suppl 4
69. Hamburger, J I 1980; Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab 50:1089-1093
70. McCowen, K, Reed, J, BL., F 1980. The role of thyroid therapy in patients with thyroid cysts. Amer J Med 68:853
71. Treece, G, Georgitis, W, Hofeldt, F 1983 Resolution of recurrent thyroid cysts with tetracycline instillation. Arch Int Med 143: 2285.
72. Monzani, F, Lippi, F, Goletti, O, et al. 1994. Percutaneous aspiration and ethanol sclero-therapy for thyroid cysts. J Clin Endocrinol Metab 78:800-802
73. Zingrillo, M, Torlontano, M, Ghiggi, M, et al. 1996. Percutaneous ethanol injection of large thyroid cystic nodules. Thyroid 6:403-8
74.Del Prete, S, Caraglia, M, Russo, D, et al. 2002 Percutaneous ethanol injection efficacy in the treatment of large symptomatic thyroid cystic nodules: ten-year follow-up of a large series. Thyroid 12:815-21
75. see 70
76. Papini, E, Bacci, V, Panunzi, C, et al. 1993. A prospective randomized trial of levothyroxine suppressive therapy for solitary thyroid nodules. Clin Endocrinol 38:507-513
77. Burch, H 1995. Evaluation and management of the solid thyroid nodule. Endocrinol Metab Clin N Am 24:663-710
78. Mainini, E, Martinelli, I, Morandi, G, Villa, S, Stefani, I, Mazzi, C 1995. Levothyroxine suppressive therapy for solitary thyroid nodule. J Endocrinol Invest 18:796-799
79. Cooper, D 1995. Clinical review 66. Thyroxine suppression therapy for benign nodular disease. J Clin Endocrinol Metab 80:331-334
80. Castro, M R, Caraballo, P J, Morris, J C 2002 Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis. J Clin Endocrinol Metab 87:4154-9
81 Zelmanovits, F, Genro, S, Gross, J 1998. Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study and cumulative meta-analyses. J Clin Endocrinol Metab 83:3881-3885
82. Herms, A, Huysmans, D 1998. Treatment of benign nodular thyroid disease. N Engl J Med 312:601-4
83. Larosa, G, Ippolito, A, Luppo, L, et al. 1996. Cold thyroid nodule reduction with l-thyroxine can be predicted by initial nodule volume and cytological characteristics. J Clin Endocrinol Metab; 81:4385-7
83.a. Sdano MT, Falciglia M, Welge JA, Steward DL. Efficacy of thyroid hormone suppression for benign thyroid nodules: meta-analysis of randomized trials Otolaryngol Head Neck Surg. 2005 Sep;133(3):391-6
84. Wemeau, J L, Caron, P, Schvartz, C, et al. 2002 Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized, double-blind, placebo-controlled trial by the French Thyroid Research Group. J Clin Endocrinol Metab 87:4928-34
85 see 77
86 Morita, T, Tamai, H, Ohshima, A, et al. 1989. Changes in serum thyroid hormone; thyrotropin and thyroglobulin concentrations during thyroxine therapy in patients with solitary thyroid nodules. J Clin Endocrinol Metab 69:227
87 Woolner, L, Beahrs, O, Black, B, McConahey, W, Keating, F J vol 12 Long term survival rates. in Hedinger Chr E (ed). Thyroid Cancer. International Union Against Cancer: Monograph Series
88. Fogelfeld, L, Wiviott, M, Shore-Freedman, E, et al. 1989. Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood for benign conditions. N Engl J Med 320:835-840
89. Bennedbaek, F, Hegedus, L 1999. Percutaneous ethanol injection therapy in benign solitary solid cold thyroid nodules. A randomized trial comparing one injection with three injections. Thyroid 9:225-233
89.1 Døssing H , Bennedbæk FN , Hegedüs L . Long-term outcome following interstitial laser photocoagulation of benign cold thyroid nodules. Eur J Endocrinol. 2011 Jul;165(1):123-8.
90. Khurana, K, Labrador, E, Izquierdo, R, Mesonero, C, Pisharodi, L 1999. The role of fine-needle aspiration biopsy in the management of thyroid nodules in children; adolescents; and young adults. A multi-institutional study. Thyroid 9:383
91.Tan, G, Gharib, H 1997. Thyroid incidentalomas. management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. AnnIntern Med126:226-31
92.Franceschi, S,Boyle, P,Maissonneuve, P,et al.1993. The epidemiology of thyroid carcinoma. Critical Reviews in Oncogenesis 4:25
93. Parkin, D, Muir, C, Whelan, S, Gao, Y, Fenlay, J, Powell, J Vol. 6 Cancer incidence in five continents. IARC Scientific Publication 120 International Agency for Research on Cancer: Lyon
94 Goodman, M, Yoshizawa, C, Kolonel, L 1988. Descriptive epidemiology of thyroid cancer in Hawaii. Cancer 61:1272
95. Spitz, M, Sider, J, Katz, R, Pollack, E, Newell, G 1988. Ethnic patterns of thyroid cancer incidence in the United States; 1973-1981. Int J Cancer 42:549
95.1. .Davies L, Welch HG Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006 May 10;295(18):2164-7.
95.2. Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, Devesa SS.Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005.Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):784-91
96. Mortensen, J, Woolner, L, Bennett, W 1955. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 15:1270
97. Silverberg, S, Vidone, R 1966. Metastatic tumors in the thyroid. Pac Med & Surg 74:175
98. Hundahl, S A, Fleming, I D, Fremgen, A M, Menck, H R 1998 A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns]. Cancer 83:2638-48
99. Wahner, H, Cuello, C, Correa, P, Uribe, L, Gaitan, E 1966. Thyroid carcinoma in an endemic goiter area; Cali; Colombia. Am J Med 40:58
100. Belfiore, La Rosa, G, La Porta, G, et al. 1992. Cancer risk in patients with cold thyroid nodules. relevance of iodine intake; sex; age; and multinodularity. Am J Med 93:363
100.1. Sandeep TC, Strachan MW, Reynolds RM, Brewster DH, Scelo G, Pukkala E, Hemminki K, Anderson A, Tracey E, Friis S, McBride ML, Kee-Seng C, Pompe-Kirn V, Kliewer EV, Tonita JM, Jonasson JG, Martos C, Boffetta P, Brennan P. Second primary cancers in thyroid cancer patients: a multinational record linkage study.J Clin Endocrinol Metab. 2006 May;91(5):1819-25
101. Namba, H, Matsuo, K, Fagin, J 1990 Clonal composition of benign and malignant human thyroid tumors. J Clin In 86:.
102. Coclet, J, Foureau, F, Ketelbant, P, Galand, P, Dumont, J 1989. Cell population kinetics in dog and human adult thyroid. Clinical Endocrinol 31:655-665
103. Curran, P, DeGroot, L 1991. The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocrine Rev 12:135-150
104. Namba, H, Gutman, R, Matsuo, K, Alvarez, A, Fagin, J 1990 H-Ras protooncogene mutations in human thyroid neoplasms. J Clin Endocrinol Metab 71: .
105. Namba, H, Rubin, S, Fagin, J 1990. Point mutations of Ras oncogenes are an early event in thyroid tumorigenesis. Molecul Endocrinol 4:1474
106. Karga, H, Lee, J-K, Vickery, A, Thor, A, Gaz, R, Jameson, J 1991. Ras oncogene mutations in benign and malignant thyroid neoplasms. J Clin Endocrinol Metab 73:832
106a. Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M, Materazzi G, Elisei R, Santoro M, Miccoli P, Basolo F. Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma.J Clin Endocrinol Metab. 2007 Nov;92(11):4085-90.
106b Costa AM , Herrero A , Fresno MF , Heymann J , Alvarez JA , Cameselle-Teijeiro J , García-Rostán G . BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2007 Dec 5
107. Santoro, M, Carlomagno, F, Hay, I, et al. 1992. Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype. J Clin Invest 89:1517-1522
108. Jhiang, S, Sagartz, J, Tong, Q, et al. 1996. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology 137:375-378
108a. Nikiforova, MN; Kimura, ET; Gandhi, M; Biddinger, PW; Knauf, JA; Basolo, F; Zhu, Z; Giannini, R; Salvatore, G; Fusco, A; Santoro, M; Fagin, JA; Nikiforov, YE. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88 5399-5404 2003.
108b. Giannini R, Ugolini C, Lupi C, Proietti A, Elisei R, Salvatore G, Berti P, Materazzi G, Miccoli P, Santoro M, Basolo F. The Heterogeneous Distribution of Distinct Tumor BRAF mutations in Multifocal Papillary J Clin Endocrinol Metab. 2007 Sep;92(9):3511-6
109 Kroff, T, Sarraf, P, Pecciarini, L, et al. 2000. PAX8-PPAR(1 fusion oncogene in human thyroid carcinoma. Science 289:1357-1360
109a. Powell, JG; Allard, BL; Sahin, M; Wang, X-L; Wang, X; Hay, ID; Hiddinga, HJ; Deshpande, SS; Kroll, TG; Grebe, SKG; Eberhardt, NL; McIver, B. The PAX8/PPAR( fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPAR( inhibition. Oncogene 2003.
110. Marques, A R, Espadinha, C, Catarino, A L, et al. 2002 Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 87:3947-52
110.1Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn II GW, Tallini G, Kroll TG, Nikiforov YE. RAS point mutations and PAX8-PPARg rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88:2318-2326, 2003.
111. Vivaldi, A, Pacini, F, Martini, F, et al. 2003 Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes. J Clin Endocrinol Metab 88:892-9
112. Puzianowska-Kuznicka, M, Krystyniak, A, Madej, A, Cheng, S Y, Nauman, J 2002 Functionally impaired TR mutants are present in thyroid papillary cancer. J Clin Endocrinol Metab 87:1120-8
112a. Takano, T; Miyauchi, A; Yoshida, H; Nakata, Y; Kuma, K; Amino, N. Expression of TR(1 mRNAs with functionally impaired mutations is rare in thyroid papillary carcinoma. J Clin Endocrinol Metab 88 3447-3449 2003.
113.Liu, R T, Huang, C C, You, H L, et al. 2002 Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas. Oncogene 21:4830-7
114. Parma, J, Duprez, L, Van Sande, J, et al. 1993. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature365:649-651
115.Suarez, H,du Villard,J, Caillou,B, Schlumberger,M, Parmentier,C, Monier,M 1991.Gsp mutationsin humanthyroid tumors.Oncogene6:677-679
116.Matsuo, K,Friedman, E,Gejman, P,Fagin, J1993. The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors. Structural studies of the TSH-R and the -subunit of GS in human thyroid neoplasms. J Clin Endocrinol Metab 76:1446-1451
117. Shi, Y, Zou, M, Farid, N 1993. Expression of thyrotrophin receptor gene in thyroid carcinoma is associated with a good prognosis. Clinical Endocrinol 39:269-274
118 Fagin, J, Matsuo, K, Karmakar, A, Chen, D, Tang, S-H, Koeffler, H 1993. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179-184
119 Wada, N, Duh, Q Y, Miura, D, Brunaud, L, Wong, M G, Clark, O H 2002 Chromosomal aberrations by comparative genomic hybridization in hurthle cell thyroid carcinomas are associated with tumor recurrence. J Clin Endocrinol Metab 87:4595-601
120. Larsson, C, Skogseid, B, Oberg, K, Nakamura, Y, Nordenskjold, M 1988. Multiple endocrine neoplasia type I gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85-87
121. Quadro, L, Panariello, L, Salvatore, D, et al. 1994. Frequent RET proto-oncogene mutations in multiple endocrine neoplasia type 2A. J Clin Endocrinol Metab 79:590-594
122. Marsh, D, Learoyd, D, Robinson, B 1995. Medullary thyroid carcinoma. Recent advances and management update. Thyroid 5:407
123. Wohllk, N, Cote, G, Bugalho, M, et al. 1996. Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 81:3740-3745
124. Loh, K C 1997 Familial nonmedullary thyroid carcinoma: a meta-review of case series. Thyroid 7:107-13.
125. Fagin, J 1997. Familial nonmedullary thyroid carcinoma – The case for genetic susceptibility. J Clin Endocrinol Metab 82:342-344
126.1 Capezzone M, Cantara S, Marchisotta S, Filetti S, De Santi MM, Rossi B, Ronga G, Durante C, Pacini F J Clin Endocrinol Metab. 2008 Oct;93(10):3950-7.
127. no entry
128. Lloyd, K, Dennis, M 1963. Cowden’s disease. A possible new symptom complex with multiple system involvement. Annals Int Med 58:136
131.Camiel, M, Mule, J, Alexander, L, Benninghoff, D 1968. Association of thyroid carcinoma with Gardner’s syndrome in siblings. N Engl J Med 278:1056
132.Parkin, J 1981. Familial multiple glomus tumors and pheochromocytomas. Ann Otol 90:.60
132a. Hemminki K, Eng C, Chen B J FAMILIAL RISKS FOR NON-MEDULLARY THYROID CANCER Clin Endocrinol Metab. 2005 Jul 19;.
133. Stratakis, C, Courcoutsakis, N, Abati, A, et al. 1997. Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation; myxomas; endocrine overactivity; and schwannomas (Carney Complex). J Clin Endocrinol Metab 82:2037-2043
134 Malchoff, C, Sarfarazi, M, Tendler, B, et al. 2000. Papillary thyroid carcinoma associated with papillary renal neoplasia. genetic linkage analysis of a distinct heritable tumor syndrome. J Clin Endocrinol Metab 85:1758-1764
134a. Malchoff, C D, Malchoff, D M 2002 The genetics of hereditary nonmedullary thyroid carcinoma. J Clin Endocrinol Metab 87:2455-9
135. Wollman, S 1963. Production and properties of transplantable tumors of the thyroid gland in the Fischer rat. Recent Prog Hormone Research 19:579
136 Frantz, V, Kligerman, M, Harland, W, Phillips, M, Quimby, E 1957. A comparison of the carcinogenic effect of internal and external irradiation on the thyroid gland of the male Long- Evans rat. Endocrinology 61:574
137 Doniach, I 1953. The effect of radioactive iodine alone and in combination with nethylthiouracil upon tumor production in the rat’s thyroid gland. Br J Cancer 7:181
138.to be entered
139.to be entered
140.Maloof, F, Dobyns, B, Vickery, A 1952. The effects of various doses of radioactive iodine on the function and structure of the thyroid of the rat. Endocrinology 50:612
141.Dobyns, B, Didtschenko, I 1961. Nuclear changes in thyroidal epithelium following radiation from radioiodine. J Clin Endocrinol Metab 21:699
142. . Duffy, B J, Fitzgerald, P 1950. Cancer of the thyroid in children. A report of twenty-eight cases. J Clin Endocrinol 10:1296
143. Clark, D 1955. Association of irradiation with cancer of the thyroid in children and adolescents. JAMA 159:1007
144. Modan, B, Ron, E, Werner, A 1977. Thyroid cancer following scalp irradiation. Therapeutic Radiology 123:741
145 DeGroot, L, Frohman, L, Kaplan, E, Refetoff, S e 1977. Radiation-Associated Thyroid Carcinoma. New York Grune & Stratton:539 pages
146. Refetoff, S, Harrison, J, Karanfilski, B, Kaplan, E, DeGroot, L, Bekerman, C 1975. Continuing occurrence of thyroid carcinoma after irradiation to the neck in infancy and childhood. N Engl J Med 292:171
147. DeGroot, L, Paloyan, E 1973. Thyroid carcinoma and radiation. A Chicago endemic. JAMA 225:487
.148.Pifer, J, Hempelmann, L, Dodge, H, Hodges, F 1968. Neoplasms in the Ann Arbor Series of thymus-irradiated children; a second survey. Am J Roent; Rad Ther & Nucl Med 103:13
149. Saenger, E, Silverman, F, Sterling, T, Turner, M 1960. Neoplasia following therapeutic irradiation for benign conditions in childhood. Radiology 74:.889
150 Beach, S, Dolphin, G 1962. A study of the relationship between X-ray dose delivered to the thyroids of children and the subsequent development of malignant tumors. Phys Med Biol 6:583
151. Winship, T, Rosvoll, R 1961. Thyroid carcinoma in childhood. Cancer 14:734
152.. Maxon, H, Thomas, S, Saenger, E, Buncher, C, Kereiakes, J 1977. Ionizing irradiation and the induction of clinically significant disease in the human thyroid gland. Am J Med 63:967
152a. Sadetzki S, Chetrit A, Lubina A, Stovall M, Novikov I. Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea capitis.J Clin Endocrinol Metab. 2006 Dec;91(12):4798-804
153. see 147
154 see 144
154a. Hollowell, JG; Staehling, NW; Flanders, WD; Hannon, WH; Gunter, EW; Spencer, CA; Braverman, LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87 489-499 2002.
155. see 152
156.Perkel, V, Gail, M, Lubin, J, et al. 1988. Radiation-induced thyroid neoplasms. Evidence for familial susceptibility factors. J Clin Endocrinol Metab 66:1316
157. Hanford, J, Quinby, E, Frantz, V 1962. Cancer arising many years after radiation therapy. JAMA 181:404
158. DeLawter, D, Winship, T 1963. Follow-up study of adults treated with Roentgen rays for thyroid disease. Cancer 16:1028
159 Parker, L, Belsky, J, Yamamoto, T, Kawamoto, S, Keehn, R 1974. Thyroid carcinoma after exposure to atomic radiation. Ann Intern Med 80:600
160.Hancock, S, Cox, R, McDougall, I 1991. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 325:599
161.Pacini, F, Vorontsova, T, Demidchik, E, et al. 1997. Post-chernobyl thyroid carcinoma in Belarus children and adolescents. Comparison with naturally occurring thyroid carcinoma in Italy and France. J Clin Endocrinol Metab 82:3563-3569
161.1.Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y, Khrouch V, Drozdovitch V, Maceika E, Zvonova I, Vlassov O, Bouville A, Goulko G, Hoshi M, Abrosimov A, Anoshko J, Astakhova L, Chekin S, Demidchik E, Galanti R, Ito M, Korobova E, Lushnikov E, Maksioutov M, Masyakin V, Nerovnia A, Parshin V, Parshkov E, Piliptsevich N, Pinchera A, Polyakov S, Shabeka N, Suonio E, Tenet V, Tsyb A,Yamashita S, Williams D. Risk of thyroid cancer after exposure to 131I in childhood J Natl Cancer Inst. 2005 May 18;97(10):724-32.
162.a Lyon JL, Alder SC, Stone MB, Scholl A, Reading JC, Holubkov R, Sheng X, White GL Jr, Hegmann KT, Anspaugh L, Hoffman FO, Simon SL, Thomas B, Carroll R, Meikle AW. Thyroid Disease Associated With Exposure to the Nevada Nuclear Weapons Test Site Radiation: A Reevaluation Based on Corrected Dosimetry and Examination Data. Epidemiology. 2006 Nov;17(6):604-614
164. Favus, J, Schneider, A, Stachura, M, et al. 1976. Thyroid cancer occurring as a late consequence of head-and-neck irradiation. N Engl J Med 294:1019
165. Maxon, H, Thomas, S, Saenger, E, Buncher, C, Kereiakes, J 1977. Ionizing irradiation and the induction of clinically significant disease in the human thyroid gland. Am J Med 63:967
166.Spitalnik, P, Straus, F 1978. Patterns of human thyroid parenchymal reaction following low-dose childhood irradiation. Cancer 41:1098
167. Roudebush, C, Asteris, G, DeGroot, L 1978. Natural history of radiation-associated thyroid cancer. Arch Intern Med 138:1631
168. Rao, D, Frame, B, Miller, M, Kleerekoper, M, Block, M, Parfitt, A 1980. Hyperparathyroidism following head and neck irradiation. Arch Intern Med 140:205
169. Conard, R 1975. A twenty-year review of medical findings in a Marshallese population accidentally exposed to radioactive fallout. Published by Brookhaven National Laboratory (BNL No. 50424) Upton: New York
169.1. Lyon JL, Alder SC, Stone MB, Scholl A, Reading JC, Holubkov R, Sheng X, White GL Jr, Hegmann KT, Anspaugh L, Hoffman FO, Simon SL, Thomas B, Carroll R, Meikle AW. Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: a reevaluation based on corrected dosimetry and examination data.Epidemiology. 2006 Nov;17(6):604-14.
170. Vickery, A The Williams & Wilkins Co Thyroid alterations due to irradiation. The Thyroid International Academy of Pathology Monograph No 5: Baltimore
171 Cantolino, S, Schmickel, R, Ball, M, Cisar, C 1966. Persistent chromosomal aberrations following radioiodine therapy for thyrotoxicosis. N Engl J Med 275:739
172. Sheline, G, Lindsay, S, McCormack, K, Galante, M 1962. Thyroid nodules occurring late after treatment of thyrotoxicosis with radioiodine. J Clin Endocrinol Metab 2: 8
173 Dobyns, B, Sheline, G, Workman, J, Tompkins, E, McConahey, W, Becker, D 1974. Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism. A report of the cooperative thyrotoxicosis therapy follow-up study. J Clin Endocrinol Metab 38:976
174 Holm, L-E, Dahlqvist, I, Israelsson, A, Lundell, G 1980. Malignant thyroid tumors after iodine 131-therapy. N Engl J Med 303:188
175 Holm, L-E, Eklund, G, Lundell, G 1980. Incidence of malignant thyroid tumors in humans after exposure to diagnostic doses of iodine-131. II. Estimation of thyroid gland size; thyroid radiation; and predicted versus observed number of malignant thyroid tumors. J Natl Cancer Inst 65:1221
176. Stanbury, J F g p 273 in Stanbury, JB; Wyngaarden, JB; Fredrickson, DS (eds). The Metabolic Basis of Inhterited Disease. New York: McGraw-Hill Book Co Inc
177. McGirr, E, Clement, W, Currie, A, Kennedy, J 1959. Impaired dehalogenase activity as a cause of goiter with malignant changes. Scott Med J 4:232
178. Elman, D 1958. Familial association of nerve deafness with nodular goiter and thyroid carcinoma. N Engl J Med 259:219
179. Medeiros-Neto, G, Oliveira, N 1970. Follicular adenocarcinoma of thyroid associated with congenital hyperplastic goiter. Acta Endocrinol Panam 1:73
180.Cooper, D, Axelrod, L, DeGroot, L, Vickery, A, Maloof, F 1981. Congenital goiter and the development of metastatic follicular carcinoma with evidence for a leak of nonhormonal iodide. Clinical; pathological; kinetic; and biochemical studies and a review of the literature. J Clin Endocrinol Metab 52:294
181. Sloan, L 1954. Of the origin; characteristics and behaviour of thyroid cancer. J Clin Endocrinol Metab 14:1309
182. Ellenbert, A, Goldman, L, Gordan, G, Lindsay, S 1962. Thyroid carcinoma in patients with hyperparathyroidism. Surgery 51:708
183. LiVolsi, V, Feind, C 1976. Parathyroid adenoma and nonmedullary thyroid carcinoma. Cancer 38:1391
184. Shapiro, S, Friedman, N, Perzik, S, Catz, B 1970. Incidence of thyroid carcinoma in Graves’ disease. Cancer 26:1261
185. see 147
186. see 184
187. Belfiore, A, Garofalo, M, Giuffrida, D, et al. 1990. Increased aggressiveness of thyroid cancer in patients with Graves’ disease. J Clin Endocrinol Metab 70:830
188. Pellegriti, G, Belfiore, A, Giuffrida, D, Lupo, L, Vigneri, R 1998. Outcome of differentiated thyroid cancer in Graves’ patients. J Clin Endocrinol Metab 83:2805
189.Filetti, S, Belfiore, A, Amir, S, et al. 1988. The role of thyroid-stimulating antibodies of Graves’ disease in differentiated thyroid cancer. N Engl J Med 318:753
191.Belfiore, A, Garofalo, M, Giuffrida, D, et al. 1990. Increased aggressiveness of thyroid cancer in patients with Graves’ disease. J Clin Endocrinol Metab 70:830
192. Valenta, L, Lemarchand-Beraud, T, Nemec, J, Griessen, M, Bednar, J 1970. Metastatic thyroid carcinoma provoking hyperthyroidism; with elevated circulating thyrostimulators. Am J Med 48:72
193. Greenspan, F, Lowenstein, J, West, M, Okerlund, M 1972. Immunoreactive material to bovine TSH in plasma from patients with thyroid cancer. J Clin Endocrinol Metab 35:795
194.Greenspan, F, Lew, W, Okerlund, M, Lowenstein, J 1974. Falsely positive bovine TSH radioimmunoassay responses in sera from patients with thyroid cancer. J Clin Endocrinol Metab 38:1121
196.Mazzaferri, E 1990. Thyroid cancer and Graves’ disease. J Clin Endocrinol Metab 70:826
197. Panza, N, Del Vecchio, L, Maio, M, et al. 1982. Strong association between an HLA- DR antigen and thyroid carcinoma. Tissue Antigens 20:155
198. Sampson, R, Woolner , L, Bahn, R, Kurland, L 1974. Occult thyroid carcinoma in Olmsted County; Minnesota. Prevalence at autopsy compared with that in Hiroshima and Nagasaki; Japan. Cancer 34:2072
199. Fukunaga, F, Yatani, R 1975. Geographic pathology of occult thyroid carcinomas. Cancer 36:1095
200 Hazard, J, Hawk, W, Crile, G J 1959. Medullary (solid) carcinoma of the thyroid. A clinicopathologic entity. J Clin Endocrinol Metab 19:152
200.1. Khurana R,. Agarwal A, Bajpai VK, Verma N, Sharma AK, Gupta RP, Madhusudan KP.Unraveling the amyloid associated with human medullary thyroid carcinoma., Endocrinology. 2004 Dec;145(12):5465-70
201. Meier, D, Woolner, L, Beahrs, O, McConahey, W 1959. Parenchymal findings in thyroid carcinoma. Pathologic study of 256 cases. J Clin Endocrinol Metab 19:162
202. Lindsay, S, Dailey, M 1955. Malignant lymphoma of the thyroid gland and its relation to Hashimoto’s disease. A clinical and pathologic study of 8 patients. J Clin Endocrinol Metab 15:1332
203. Rayfield, E, Nishiyama, R, Sisson, J 1971. Small cell tumors of the thyroid. A clinicopathologic study. Cancer 28:1023
204. Black, B, Kirk, T J, Woolner, L 1960. Multicentricity of papillary adenocarcinoma of the thyroid. Influence on treatment. J Clin Endocrinol Metab 20:130
205. Iida, F, Yonekura, M, Miyakawa, M 1969. Study of intraglandular dissemination of thyroid cancer. Cancer 24:764
205.1 Giannini R, Ugolini C, Lupi C, Proietti A, Elisei R, Salvatore G, Berti P, Materazzi G, Miccoli P, Santoro M, Basolo F. The heterogeneous distribution of BRAF mutation supports the independent clonal origin of distinct tumor foci in multifocal papillary thyroid carcinoma. J Clin Endocrinol Metab. 2007 Sep;92(9):3511-6.
206. Reed, R, Russin, D, Krementz, ET. 1966. Latent metastases from occult sclerosing carcinoma of the thyroid. JAMA 196:233
207. Hazard, J 1960. Small papillary carcinoma of the thyroid. Lab Invest 9:86
208. Studer, H, Veraguth, P, Wyss, F 1961. Thyrotoxicosis due to a solitary hepatic metastasis of thyroid carcinoma. J Clin Endocrinol Metab 21:1334
209. Hunt, W, Crispell, K, McKee, J 1960. Functioning metastatic carcinoma of the thyroid producing clinical hyperthyroidism. Am J Med 28:995
210. Pochin, E 1960. Leukemia following radioiodine treatment of thyrotoxicosis. Br Med J 2:1545
211. Wyse, E, Hill, C, Ibanez, M, Clark, R 1969. Other malignant neoplasms associated with carcinoma of the thyroid. Thyroid carcinoma multiplex. Cancer 24:701
212. Shimaoka, K, Takeuchi, S, Pickren, J 1967. Carcinoma of thyroid associated with other primary malignant tumors. Cancer 20:1000
213. Halnan, K 1966. Influence of age and sex on incidence and prognosis of thyroid cancer. Cancer 19:1534
214. Russel, M, Gilbert, E, Jaeschke, W 1975. Prognostic features of thyroid cancer. A long term follow-up of 68 cases. Cancer 36:553
215. see 213
216. Rosvoll, R, Winship, T 1965. Thyroid carcinoma and pregnancy. Surg Gynecol Obstet 121:1039
217. Franssila, K 1975. Prognosis in thyroid carcinoma. Cancer 36:1138
218.Woolner, L, Lemmon, M, Beahrs, O, Black, B, Keating, F J 1960. Occult papillary carcinoma of the thyroid. Study of 140 cases observed in a 30-year period. J Clin Endocrinol Metab 20:89-113
218a. Passler, C; Prager, G; Scheuba, C; Niederle, BE; Kaserer, K; Zettinig, G; Niederle, B. Follicular variant of papillary thyroid carcinoma: a long-term follow-up. Arch Surg 138 1362-1366 2003.
218b. Shattuck TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med. 2005 Jun 9;352(23):2406-12.
219.McConahey, W, Taylor, W, Gorman, C, Woolner, L Field Educational Italia Retrospective study of 820 patients treated for papillary carcinoma of the thyroid at the Mayo Clinic between 1946 and 1971. in Andreoli, M; Monaco, F; Robbins, J (eds). Advances in Thyroid Neoplasia: Rome
220. Franssila, K 1975. Prognosis in thyroid carcinoma. Cancer 36:1138
221. McDermott, W J, Morgan, W, Hamlin, E J, Cope, O 1954. Cancer of the thyroid. J Clin Endocrinol Metab 14:1336
222 Schlumberger, M, De Vathaire, F, Travagli, J, et al. 1987. Differentiated thyroid carcinoma in childhood. Long term follow-up of 72 patients. J Clin Endocrinol Metab 65:1088
223 Cady, B, Sedgwick, C, Meissner, W, Bookwalter, J, Romagosa, V, Werber, J 1976. Changing clinical; pathologic; therapeutic; and survival patterns of differentiated thyroid carcinoma. Ann Surg 184:541
224. Mazzaferri, E, Young, R 1981. Papillary thyroid carcinoma. A ten year follow-up report of the impact of therapy in 576 patients. Am J Med 70:511
225. see 223
256 Harwood, J, Clark, O, Dunphy, J 1978. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg 136:107
257. Mazzaferri, E, Young, R, Oertel, J, Kemmerer, W, Page, C 1977. Papillary thyroid carcinoma. The impact of therapy in 576 patients. Medicine 56:171
258. Terry, J, St John, S, Karkowski, F, al., e 1994. Tall cell papillary thyroid cancer. Incidence and prognosis. Am J Surg 168:459
259. Burman, K, Ringel, M, Wartofsky, L 1996. Unusual types of thyroid neoplasms. Endocrinol Metab Clinics North America 25:49-68
259.1. Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R, Romei C, Miccoli P, Pinchera A, Basolo F BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008 Oct;93(10):3943-9
263.Frazell, E, Duffy, B 1954. Invasive papillary cancer of the thyroid. J Clin Endocrinol Metab 14:1362
264. Franssila, K 1975. Prognosis in thyroid carcinoma. Cancer 36:1138
265. Woolner, L, Lemmon, M, Beahrs, O, Black, B, Keating, F J 1960. Occult papillary carcinoma of the thyroid. Study of 140 cases observed in a 30-year period. J Clin Endocrinol Metab 20:89
266. see 223
266a. Chao, TC; Lin, JD; Chen, MF. Insular carcinoma: Infrequent subtype of thyroid cancer with aggressive clinical course. World J Surg 2004.
267. Young, R, Mazzaferri, E, Rahe, A, Dorfman, S 1980. Pure follicular thyroid carcinoma. Impact of therapy in 214 patients. J Nucl Med 21:733
268. Justin, E, Seabold, J, Robinson, R, Walker, W, Gurll, N, Hawe, D 1991. Insular carcinoma. A distinct thyroid carcinoma with associated Iodine-131 localization. J Nucl Med 32:1358-1363
268.1. Pulcrano M, Boukheris H, Talbot M, Caillou B, Dupuy C, Virion A, De Vathaire F, Schlumberger M. Poorly Differentiated Follicular Thyroid Carcinoma: Prognostic Factors and Relevance of Histological Classification. Thyroid. 2007 Jul;17(7):639-646
269. McDermott, W J, Morgan, W, Hamlin, E J, Cope, O 1954. Cancer of the thyroid. J Clin Endocrinol Metab 14:1336
270. see 267
272. see 223
273. see 267
274. Caplan, R, Abellera, R, Kisken, W 1994. Hurthle cell neoplasms of the thyroid gland. Reassessment of functional capacity. Thyroid 4:243
275. Cheung, C, Ezzat, S, Ramyar, L, Freeman, J, Asa, S 2000. Molecular basis of Hurthle cell papillary thyroid carcinoma. J Clin Endocrinol Metab 85:878-882
276 see 274
277. Harada, T, Ito, K, Shimaoka, K, Hosoda, Y, Yakumara, K 1977. Fatal thyroid carcinoma. Anaplastic transformation of adenocarcinoma. Cancer 39:2588
278. Oppenheim, al., e 1983. Analplastic thyroid cancer presenting with hyperthyroidism. Amer J Med 75:702
279. Leedman, P, Sheridan, W, Downey, W, Fox, R, Martin, F 1990. Combination chemotherapy as single modality therapy for stage IE and IIE thyroid lymphoma. Med J Australia 152:40
280. Butler, J, Brady, L, Amendola, B 1990. Lymphoma of the thyroid. Report of five cases and review. Amer J Clin Oncol (CCT) 13:64
281. Souhami, L, Simpson, W, Carrothers, J 1980. Malignant lymphoma of the thyroid gland. Int J Radiat Oncol Biol Phys 6:1143
282. Kini, S, Miller, J, Hamburger, J 1981. Problems in the cytologic diagnosis of the “cold” thyroid nodule in patients with lymphocytic thyroiditis. Acta Cytol 25:506
283 Grimley, R, Oates, G 1980. The natural history of malignant thyroid lymphomas. Br J Surg 67:475
284. Siroto, D, Segal, R 1979. Primary lymphomas of the thyroid. JAMA 242:1743
284a Sandeep TC, Strachan MW, Reynolds RM, Brewster DH, Scelo G, Pukkala E, Hemminki K, Anderson A, Tracey E, Friis S, McBride ML, Kee-Seng C, Pompe-Kirn V, Kliewer EV, Tonita JM, Jonasson JG, Martos C, Boffetta P, Brennan P. Second primary cancers in thyroid cancer patients: a multinational record linkage study J Clin Endocrinol Metab. 2006 May;91(5):1819-25
284bBrown AP , Chen J , Hitchcock YJ , Szabo A , Shrieve DC , Tward JD . The Risk of Second Primary Malignancies up to Three Decades after the Treatment of Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2008 Feb;93(2):504-15.
285.Cignarelli, M, Ambrosi, A, Marino, A, Lamacchia, O, Cincione, R, Neri, V 2002 Three cases of papillary carcinoma and three of adenoma in thyroglossal duct cysts: clinical-diagnostic comparison with benign thyroglossal duct cysts. J Endocrinol Invest 25:947-54
286. Hazard, J, Hawk, W, Crile, G J 1959. Medullary (solid) carcinoma of the thyroid. A clinicopathologic entity. J Clin Endocrinol Metab 19:152
287. see 22
289. Suarez, H, du Villard, J, Caillou, B, Schlumberger, M, Parmentier, C, Monier, M 1991. Gsp mutations in human thyroid tumors. Oncogene 6:677-679
290. Manning, P, Molnar, G, Black, M, Priestley, J, Woolner, L 1963. Pheochromocytoma; hyperparathyroidism; and thyroid carcinoma occurring coincidentally. N Engl J Med 268:68
291. Gorlin, R, Sedano, H, Vickers, R, Cervenka, J 1968. Multiple mucosal neuromas; pheochromocytoma; and medullary carcinoma of the thyroid — a syndrome. Cancer 22:293
292. no entry
293. Gagel, R, Robinson, M, Donovan, D, Alford, B 1993. Medullary thyroid carcinoma. Recent progress. J Clin Endocrinol Metab 76:.809-814
294. Carney, J, Go, V, Sizemore, G, Hayles, A 1976. Alimentary-tract ganglioneuromatosis. N Engl J Med 295:1287
295 Noel, M, Delehaye, M-C, Segond, N, et al. 1991. Study of calcitonin and thyroglobulin gene expression in human mixed follicular and medullary thyroid carcinoma. Thyroid 1:249
296.DeGroot, L, Hoye, K, Refetoff, S, Van Herle, A, Asteris, G, Rochman, H 1977. Serum antigens and antibodies in the diagnosis of thyroid cancer. J Clin Endocrinol Metab 45:1220
297.Sobol, H, Narod, S N, Y, Boneu, A, et al. 1989. Screening for multiple endocrine neoplasia type 2a with DNA-polymorphism analysis. N Engl J Med 321:996-1001
298. Wolfe, H, Melvin, K, Cervi-Skinner, S, et al. 1973. C-cell hyperplasia preceding medullary thyroid carcinoma. N Engl J Med 289:437
299. Cox, T, Fagan, E, Hillyard, C, Allison, D, Chadwick, V 1979. Role of calcitonin in diarrhea associated with medullary carcinoma of the thyroid. Gut 20:629
300 Pacini, F, Basolo, F, Elisel, R, Fugazzola, L, Cola, A, Pinchera, A Amer J Clin Pathol. 95 300: 1991.
301- Kanamoto N, Akamizu T, Hosoda H, Hataya Y, Ariyasu H, Takaya K, Hosoda K, Saijo M, Moriyama K, Shimatsu A, Kojima M, Kangawa K, and Nakao K. Substantial production of Ghrelin by a human medullary thyroid carcinoma cell line. J Clin Endocrinol Metab 86:4984-4990, 2001
302. Cohen, S, Graham-Smith, D, MacIntyre, I, Walker, J 1973. Alcohol- stimulated calcitonin release in medullary carcinoma of the thyroid. Lancet 2:1172
303.Melvin, K, Tashjian, A 1968. The syndrome of excessive thyrocalcitonin produced by medullary carcinoma of the thyroid. Proc Natl Acad Sci USA 59:1216
305.. Larsson, C, Skogseid, B, Oberg, K, Nakamura, Y, Nordenskjold, M 1988. Multiple endocrine neoplasia type I gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85-87
306 Quadro, L, Panariello, L, Salvatore, D, et al. 1994. Frequent RET proto-oncogene mutations in multiple endocrine neoplasia type 2A. J Clin Endocrinol Metab 79:590-594
307. Marsh, D, Learoyd, D, Robinson, B 1995. Medullary thyroid carcinoma. Recent advances and management update. Thyroid 5:407
308. Wohllk, N, Cote, G, Bugalho, M, et al. 1996. Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 81:3740-3745
309. Melvin, K, Miller, H, Tashjian, A 1971. Early diagnosis of medullary carcinoma of the thyroid gland by means of calcitonin assay. N Engl J Med 285:1115
310. Wahner, H, Cuello, C, Aljure, F 1968. Hormone-induced regression of medullary (solid) thyroid carcinoma. Am J Med 45:789
311. Barbot, N, Calmettes, C, Schuffenecker, I, et al. 1994. Pentagastrin stimulation test and early diagnosis of medullary thyroid carcinoma using an immunoradiometric assay of calcitonin. Comparison with genetic screening in hereditary medullary thyroid carcinoma. J Clin Endocrinol Metab 78:114-120
312. see 311
313. Calmettes, C, Moukhtar, M, Milhaud, G 1977. Correlation between calcitonin and carcinoembryonic antigen levels in medullary carcinoma of the thyroid. Biomedicine 27:52
314. Hoefnagel, C, Delprat, C, Zanin, D, Van Der Schoot, J 1988. New radionuclide tracers for the diagnosis and therapy of medullary thyroid carcinoma. Clin Nucl Med 13:159
315. see 311
316. Pacini, F, Ceccherini, I, Martino, E, et al. Abstract No. 182. Screening for ret gene mutations in multiple endocrine neoplasia (MEN) type 2 and in sporadic medullary thyroid carcinoma (MTC). clinical applications. Sixty-eighth annual meeting of the American Thyroid Association Chicago; IL: September 28-October 1; 1994
317. Sobol, H, Narod, S N, Y, Boneu, A, et al. 1989. Screening for multiple endocrine neoplasia type 2a with DNA-polymorphism analysis. N Engl J Med 321:996-1001
318. Lips, C, Landsvater, R, Hoppener, J, et al. 1994. Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331:828-835
319. Black, H, Capen, C, Young, D 1973. Ultimobranchial thyroid neoplasms in bulls. Cancer 32:865
319a. Machens, A; Niccoli-Sire, P; Hoegel, J; Frank-Raue, K; van Vroonhoven, TJ; Roeher, H-D; Wahl, RA; Lamesch, P; Raue, F; Conte-Devolx, B; Dralle, H. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349 1517-1525 2003.
320.Graze, K, Spiler, I, Tashijan, A J, et al. 1978. Natural history of familial medullary thyroid carcinoma. N Engl J Med 299:980
320.1 Scollo C, Baudin E, Travagli J-P, Caillou B, Bellon N, Leboulleux S, Schlumberger M. Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070-2075, 2003.
321. . Deftos, L, Stein, M 1980. Radioiodine as an adjunct to the surgical treatment of medullary thyroid carcinoma. J Clin Endocrinol Metab 50:967
322. Hellman, D, Kartchner, M, Van Antwerp, J, Salmon, S, Patton, D, O’Mara, R 1979. Radioiodine in the treatment of medullary carcinoma of the thyroid. J Clin Endocrinol Metab 48:451
323. Kim, S, Morimoto, S, Kawa, i Y, Koh, E, Onishi, T, Ogihara, T 1989. Circulating levels of calcitonin gene-related peptide in patients with medullary thyroid carcinoma. J Clin Chem Clin Biochem 27:423
324. Moley, J, Wells, S, Dilley, W, Tisell, L 1993. Reoperation for recurrent or persistent medullary thyroid cancer. Surgery 114:1090-1095
325. Frank-Raue, K, Raue, F, Buhr, H, Baldauf, G, Lorenz, D, Ziegler, R 1992. Localization of occult persisting medullary thyroid carcinoma before microsurgical reoperation. High sensitivity of selective venous catheterization. Thyroid 2:113
326. Simpson, W 1975. Radiotherapy in thyroid cancer. Can Med Assoc J 113:115
327. Brierley, J, Tsang, R, Simpson, W, Gospodarowicz, M, Sutcliffe, S, Panzarella, T 1996. Medullary thyroid cancer. Analyses of survival and prognostic factors and the role of radiation therapy in local control. Thyroid 6:305-310
328. Fersht, N, Vini, L, A’Hern, R, Harmer, C 2001 The role of radiotherapy in the management of elevated calcitonin after surgery for medullary thyroid cancer. Thyroid 11:1161-8
329. Samaan, N, Schultz, P, Hickey, R Medullary thyroid carcinoma. Prognosis of familial versus nonfamilial disease and the role of radiotherapy.
330. Hoefnagel, C, Delprat, C, Zanin, D, Van Der Schoot, J 1988. New radionuclide tracers for the diagnosis and therapy of medullary thyroid carcinoma. Clin Nucl Med 13:159
331 DeGroot, L 1970. Lack of iodide trapping in “cold” thyroid nodules. Acta Endocrinol Panam 1:27
332. Kim, B W, Daniels, G H, Harrison, B J, et al. 2003 Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels. J Clin Endocrinol Metab 88:594-8
333. Huang, S A, Fish, S A, Dorfman, D M, et al. 2002 A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase. J Clin Endocrinol Metab 87:4457-61
334. Abe, Y, Ichikawa, Y, Muraki, T, Ito, K, Momma, M 1981. Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors. Absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma. J Clin Endocrinol Metab 52:23
335.Carayon, P, Thomas-Morvan, C, Castanas, E, Tubiana, M 1980. Human thyroid cancer. Membrane thyrotropin binding and adenylate cyclase activity. J Clin Endocrinol Metab 51:915
336. 1. Burke, G, Szabo, M 1972. Dissociation of in vivo and in vitro “autonomy” in hyperfunctioning thyroid nodules. J Clin Endocrinol Metab 35:199
337. 1. Van Sande, J, Mockel, J, Boeynaems, J, Dor, P, Andry, G, Dumont, J 1980. Regulation of cyclic nucleotide and prostaglandin formation in normal human thyroid tissue and in autonomous nodules. J Clin Endocrinol Metab 50:776
337a. Castro P, Rebocho AP, Soares RJ, Magalhaes J, Roque L, Trovisco V, Vieira de Castro I, Cardoso-de-Oliveira M, Fonseca E, Soares P, Sobrinho-Simoes M. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma J Clin Endocrinol Metab. 2006 Jan;91(1):213-20.
337b.Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, Carson KA, Vasko V, Larin A, Tallini G, Tolaney S, Holt EH, Hui P, Umbricht CB, Basaria S, Ewertz M, Tufaro AP, Califano JA, Ringel MD, Zeiger MA, Sidransky D, Ladenson PW. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer J Clin Endocrinol Metab. 2005 Dec;90(12):6373-9
337.c Guarino V, Faviana P, Salvatore G, Castellone MD, Cirafici AM, De Falco V,Celetti A, Giannini R, Basolo F, Melillo RM, Santoro M. Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. Clin Endocrinol Metab. 2005 Sep;90(9):5270-8
338. 1. Franklin, W, Mariotti, S, Kaplan, D, DeGroot, L 1982. Immunofluorescence localization of thyroglobulin in metastatic thyroid cancer. Cancer 50:939
339. Goudie, R, McCallum, H 1963. Loss of tissue-specific autoantigens in thyroid tumors. Lancet 1:348
340. Pontius, K, Hawk, W 1980. Loss of microsomal antigen in follicular and papillary carcinoma of the thyroid. An immunofluorescence and electron-microscope study. Am J Pathol 74:620
341. Meier, D, Woolner, L, Beahrs, O, McConahey, W 1959. Parenchymal findings in thyroid carcinoma. Pathologic study of 256 cases. J Clin Endocrinol Metab 19:162
342.to be entered
343. to be entered
344 DeGroot, L, Hoye, K, Refetoff, S, Van Herle, A, Asteris, G, Rochman, H 1977. Serum antigens and antibodies in the diagnosis of thyroid cancer. J Clin Endocrinol Metab 45:1220
345 Aoki, N, DeGroot, L 1979. Lymphocyte blastogenic response to human thyroglobulin in Graves’ disease; Hashimoto;s thyroiditis; and metastatic thyroid cancer. Clin Exp Immunol 38:523
346. Amino, N, Pysher, T, Cohen, E, DeGroot, L 1975. Immunologic aspects of human thyroid cancer. Cancer 36:963
347. Mariotti, S, DeGroot, L, Scarborough, D, Medof, M 1979. Study of circulating immune complexes in thyroid diseases. Comparison of Raji cell radioimmunoassay and specific thyroglobulin-antithyroglobulin radioassay. J Clin Endocrinol Metab 49:679
348. Pacini, F, Mariotti, S, Formica, N, et al. 1988 Thyroid autoantibodies in thyroid cancer. Incidence and relationship with tumour outcome. Acta Endocrinol (Copenh) 119:373
349. Rubello, D, Casara, D, Girelli, M, Piccolo, M, Busnardo, B 1992. Clinical meaning of circulating antithyroglobulin antibodies in differentiated thyroid cancer. a prospective study. J Nucl Med 33:1478
350. Rocklin, E, Gagel, R, Feldman, Z, Tashijan, A J 1977. Cellular immune responses in familial medullary thyroid carcinoma. N Engl J Med 296:835
351. Belfiore, A, Garofalo, M, Giuffrida, D, et al. 1990. Increased aggressiveness of thyroid cancer in patients with Graves’ disease. J Clin Endocrinol Metab 70:830
352. Pellegriti, G, Belfiore, A, Giuffrida, D, Lupo, L, Vigneri, R 1998. Outcome of differentiated thyroid cancer in Graves’ patients. J Clin Endocrinol Metab 83:2805
353.Filetti, S, Belfiore, A, Amir, S, et al. 1988. The role of thyroid-stimulating antibodies of Graves’ disease in differentiated thyroid cancer. N Engl J Med 318:753
354. Wu, P-C, Leslie, P, McLaren, K, Toft, A 1989. Diffuse sclerosing papillary carcinoma of thyroid. A wolf in sheep’s clothing. Clin Endocrinol 31:535
355. Cignarelli, M, Triggiani, V, Ciampolillo, A, et al. 2001. High frequency of incidental diagnosis of extrathyroidal neoplastic diseases at the fine-needle aspiration biopsy of laterocervical lymph nodes in patients with thyroid nodules. Thyroid 11:65
356. Van Herle, A, Uller, R 1975. Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas. J Clin Invest 56:272
356a. Costante G , Meringolo D , Durante C , Bianchi D , Nocera M , Tumino S , Crocetti U , Attard M , Maranghi M , Torlontano M , Filetti S Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab. 2007 Feb;92(2):450-5
357. Meighan, J, Dworkin, H 1969. Failure to detect 131I positive thyroid metastases with 99mTc. J Nucl Med 11:173
358. Fairweather, D, Bradwell, A, Watson-James, S, Dykes, P, Chandler, S, Hoffenberg, R 1983. Detection of thyroid tumors using radio-labelled thyroglobulin. Clin Endocrinol 18:563
359. O’Byrne, K, Hamilton, D, Robinson, I, al., e 1992. Imaging of medullary carcinoma of the thyroid using 111In-labelled anti-CEA monoclonal antibody fragments. Nucl Med Commun 13:142
360. Thomas, C, Pepper, F, Owen, J 1969. Differentiation of malignant from benign lesions of the thyroid gland using complementary scanning with 75Selenomethionine and radioiodide. Ann Surg 170:396
361 Yano, K, Morita, S, Furukawa, Y, al., e 1978. Diagnosis of malignant neoplasms with 201Ti chloride. Jpn J Nucl Med 15:989
362. to be added
363. Higashi, T, Ito, K, Nishikawa, Y, al., e 1988. Gallium-67 imaging in the evaluation of thyroid malignancy. Clin Nucl Med 13:792
364. Skowsky, W, Wilf, L 1991. 131Iodine metaiodobenzylguanidine scintigraphy of medullary carcinoma of the thyroid. South Med J 84:636
365.Lamberts, S, Reubi, J-C, Krenning, E 1993. Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors. Acta Oncol 32:167
367. Wang, W, Larson, S, Fazzari, M, et al. 2000. Prognostic value of [18F]-Fluorodeoxy-glucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 85:1107-1113
367.1 van Tol KM, Jager PL, Piers A, Pruim J, de Vries EGE, Dullaart RPF, Links TP. Better yield of 18Fluorodeoxyglucose-positron emission tomography in patients with metastatic differentiated thyroid carcinoma during thyrotropin stimulation. Thyroid 12:381, 2002.
367a. Chin, BB; Patel, P; Cohade, C; Ewertz, M; Wahl, R; Ladenson, P. Recombinant human thyrotropin stimulation of fluoro-D-glucose positron emission tomography uptake in well-differentiated thyroid carcinoma. J Clin Endocrinol Metab 89 91-95 2004.
367b. Kim JM, Ryu JS, Kim TY, Kim WB, Kwon GY, Gong G, Moon DH, Kim SC, Hong SJ, Shong YK. 18F-fluorodeoxyglucose positron emission tomography does not predict malignancy in thyroid nodules cytologically diagnosed as follicular neoplasm.J Clin Endocrinol Metab. 2007 May;92(5):1630-4
368. Ridder, R, Willeke, F, Lacroix, J, et al. Detection of thyroglobulin mRNA in peripheral blood of patients with thyroid cancer.
369a. Elisei, R; Vivaldi, A; Agate, L; Molinaro, E; Nencetti, C; Grasso, L; Pinchera, A; Pacini, F. Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents its use in the follow-up of differentiated thyroid cancer patients. J Clin Endocrinol Metab 89 29-32 2004.
369b. Chia SY, Milas M, Reddy SK, Siperstein A, Skugor M, Brainard J, Gupta MK. Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.J Clin Endocrinol Metab. 2007 Feb;92(2):468-75
370. Harmer, M Springer-Verlag Application of TNM classification rules to malignant tumors of the thyroid gland; in Hedinger CE (ed). Thyroid Cancer. UICC Monograph Series 12.64: Berlin
371. Sobin LH, Wittekind Ch (eds) TNM Classification of Malignant Tumors, 6th Edition . Wiley-Liss, New YOrk, pp 52-56
371a. Tennvall J, Biorklund A, Moller T et al. Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid Carcinoma? Cancer 57:1405, 1986
371b. Pasieka JL, Zedenius J, Azuer G et al; Addition of nuclear content to the AMES risk-group classification for papillary thyroid cancer: Surgery 112:1154, 1992.
371c. Hay ID, Bergstralh EJ, Goellner JR, et al. Predicting outcome in papillary thyroid carcinoma. Surgery 114: 1050, 1993.
372. Yano, K, Morita, S, Furukawa, Y, al., e 1978. Diagnosis of malignant neoplasms with 201Ti chloride. Jpn J Nucl Med 15:989
373. Van Herle, A, Uller, R 1975. Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas. J Clin Invest 56:272
374. see 370
375. to be added
376. Buckwalter, J, Thomas, C 1972. Selection of surgical treatment for well differentiated thyroid carcinomas. Ann Surg 176:565
377. Tollefsen, H, Shah, J, Huvos, A 1972. Papillary carcinoma of the thyroid. Recurrence in the thyroid gland after initial surgical treatment. Am J Surg 124:468
378. Rickey, O, Howard, R 1967. Cancer of the thyroid. Am J Surg 112:637
379. to be added
380. Clark, R, Ibanez, M, White, E 1966. What constitutes an adequate operation for carcinoma of the thyroid? Arch Surg 92:23
381. Rustad, W, Lindsay, S, Dailey, M 1963. Comparison of the incidence of complications following total and subtotal thyroidectomy for thyroid carcinoma. Surg Gynecol Obstet 116:109
382. Thompson, N, Harness, J; 1970. Complications of total thyroidectomy for carcinoma. Surg Gynecol Obstet 131:861
383. Samaan, N, Schultz, P, Hickey, R, et al. 1992. The results of various modalities of treatment of well differentiated thyroid carcinoma. A retrospective review of 1599 patients. J Clin Endocrinol Metab 75:714-720
384. Tollefson, H, DeCosse, J 1964. Papillary carcinoma of the thyroid. The case for radical neck dissection. Am J Surg 108:547
385. Crile, G J, Suhrer, J J, Hazard, J 1955. Results of conservative operations for malignant tumors of the thyroid. J Clin Endocrinol Metab 15:1422
386. Crile, G J 1971. Changing end results in patients with papillary carcinoma of the thyroid. Surg Gynecol Obstet 132:460
387.Glass, H, Waldron, G, Allen, H J, Brown, W 1960. A rational approach to the thyroid malignancy problem. Am Surg 26:81
390. Cady, B, Sedgwick, C, Meissner, W, Bookwalter, J, Romagosa, V, Werber, J 1976. Changing clinical; pathologic; therapeutic; and survival patterns of differentiated thyroid carcinoma. Ann Surg 184:541
391. see 376.
392. see 376
394. Shands, W, Gatling, R 1970. Cancer of the thyroid. Review of 109 cases. Ann Surg 171:735
396. see 384
398. to be entered
400. see 378
402. see 376
404. see 380
406. see 378
400. Tollefsen, H, Shah, J, Huvos, A 1972. Papillary carcinoma of the thyroid. Recurrence in the thyroid gland after initial surgical treatment. Am J Surg 124:468
401. Rosvoll, R, Winship, T 1965. Thyroid carcinoma and pregnancy. Surg Gynecol Obstet 121:1039
402. Samaan, N, Schultz, P, Hickey, R, et al. 1992. The results of various modalities of treatment of well differentiated thyroid carcinoma. A retrospective review of 1599 patients. J Clin Endocrinol Metab 75:714-720
403. Hay, I, Grant, C, Bergstralh, E, Thompson, G, van Heerden, J, Goellner, J 1998. Unilateral total lobectomy. Is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124:958-966
404. Rustad, W, Lindsay, S, Dailey, M 1963. Comparison of the incidence of complications following total and subtotal thyroidectomy for thyroid carcinoma. Surg Gynecol Obstet 116:109
405. Thompson, N, Harness, J; 1970. Complications of total thyroidectomy for carcinoma. Surg Gynecol Obstet 131:861
406. Mazzaferri, E, Young, R, Oertel, J, Kemmerer, W, Page, C 1977. Papillary thyroid carcinoma. The impact of therapy in 576 patients. Medicine 56:171
407. Tollefson, H, DeCosse, J 1964. Papillary carcinoma of the thyroid. The case for radical neck dissection. Am J Surg 108:547
408. see 407
409. Glass, H, Waldron, G, Allen, H J, Brown, W 1960. A rational approach to the thyroid malignancy problem. Am Surg 26:81
410. Hirabayashi, R, Lindsay, S 1961. Carcinoma of the thyroid gland–a statistical study of 390 patients. J Clin Endocrinol Metab 21:1596
411. Hay, I, Bergstralh, E, Goellner, J, Ebersold, J, Grant, C 1993. Predicting outcome in papillary thyroid carcinoma. development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 114:1050-1057
412Meissner, W, Colcock, B, Achenback, H 1955. The pathologic evaluation of radical neck dissection for carcinoma of the thyroid gland. J Clin Endocrinol Metab 15:1432
412.1 Bonnet S, Hartl D, Leboulleux S, Baudin E, Lumbroso JD, Al Ghuzlan A, Chami L, Schlumberger M, Travagli JP. Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment. J Clin Endocrinol Metab. 2009 Apr;94(4):1162-7.
412.2 Chung YS, Kim JY, Bae JS, Song BJ, Kim JS, Jeon HM, Jeong SS, Kim EK, Park WC. Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid. 2009 Mar;19(3):241-6.
412.3 Lim YC, Choi EC, Yoon YH, Kim EH, Koo BS. Central lymph node metastases in unilateral papillary thyroid microcarcinoma. Br J Surg. 2009 Mar;96(3):253-7.
412.4 White ML, Gauger PG, Doherty GM. Central lymph node dissection in differentiated thyroid cancer. World J Surg. 2007 May;31(5):895-904.
414. Block, G, Wilson, S 1971. A modified neck dissection for carcinoma of the thyroid. Surg Clin North Am 51:139
415. Mustard, R 1970. Treatment of papillary carcinoma of the thyroid with emphasis on conservative neck dissection. Am J Surg 120:697
416. McGovern, J, Mannex, H J 1967. Thirty year experience with thyroid cancer. NY State J Med 67:2207
417. Exelby, P, Frazell, E 1969. Carcinoma of the thyroid in children. Surg Clin North Am 49:249
418. Werk, E, Vernon, B, Gonzalez, J, Ungaro, P, McCoy, R 1984. Cancer in thyroid nodules. A community hospital survey. Arch Intern Med 144:474
418a Triponez F, Poder L, Zarnegar R, Goldstein R, Roayaie K, Feldstein V, Lee J, Kebebew E, Duh QY, Clark OH. Hook needle-guided excision of recurrent differentiated thyroid cancer in previously operated neck compartments: a safe technique for small, nonpalpable recurrent disease.J Clin Endocrinol Metab. 2006 Dec;91(12):4943-7
419. Klapp, C, Rosvoli, R, Winship, T 1967. Is destructive surgery ever necessary for treatment of thyroid cancer in children? Ann Surg 165:745
420. Wolf, G, Kohek, P, Geyer, E, et al. 1996. Intraoperative radiation therapy; endotracheal hyperthermia and IR-192-brachytherapy in patients with advanced thyroid cancer. Acta Medica Austriaca 23:76-79
421. Nishida, T, Nakao, K, Hamaji, M 1997. Differentiated thyroid carcinoma with airway invasion. Indication for tracheal resection based on the extent of cancer invasion. J Thorac Cardiovas Surg 114:84-92
422. Ozaki, O, Sugino, K, Mimura, T, Ito, K 1995. Surgery for patients with thyroid carcinoma invading the trachea. Circumferential sleeve resection followed by end-to-end anastomosis. Surgery 117:268-271
423. Sugenoya, A, Matsuo, K, Asanuma, K, et al. 1995. Management of tracheal wall resection for thyroid carcinoma by tracheocutaneous fenestration and delayed closure using auricular cartilage. Head & Neck 17:339-342
424. Schlumberger, M, Arcangioli, O, Piekarski, J, Tubiana, M, Parmentier, C 1988. Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays. J Nucl Med 29:1790-1794
425. Ruegemer, J, Hay, I, Bergstralh, E, Ryan, J, Offord, K, Gorman, C 1988. Distant metastases in differentiated thyroid carcinoma. A multivariate analysis of prognostic variables. J Clin Endocrinol Metab 67:501-508
425.1 Hovens GC, Stokkel MP, Kievit J, Corssmit EP, Pereira AM, Romijn JA, Smit JW. Associations of serum thyrotropin concentrations with recurrence and death in differentiated thyroid cancer. J Clin Endocrinol Metab. 2007 Jul;92(7):2610-5.
426. Exelby, P, Frazell, E 1969. Carcinoma of the thyroid in children. Surg Clin North Am 49:249
427. Klapp, C, Rosvoli, R, Winship, T 1967. Is destructive surgery ever necessary for treatment of thyroid cancer in children? Ann Surg 165:745
428. Liechty, R, Safaie-Shirazi, S, Soper, R 1972. Carcinoma of the thyroid in children. Surg Gynecol Obstet 134:595
429. Pacini, F, Gasperi, M, Fugazzola, L, et al. 1994. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine. J Nucl Med 35:1418
430. McClellan, D, Francis, G 1996. Thyroid cancer in children; pregnant women; and patients with Graves’ disease. Endocrinol Metab Clinics North America 25:27-48
431. Casara, D, Rubello, D, Saladini, G, et al. 1993. Pregnancy after therapeutic doses of iodine-131 in differentiated thyroid cancer. potential risks and recommendations. Eur J Nucl Med 20:192
432. Schlumberger, M, De Vathaire, F, Ceccarelli, C, et al. 1996. Exposure to radioactive iodine-131 for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients. J Nucl Med 37:606
433. Schlumberger, M, De Vathaire, F, Travagli, J, et al. 1987. Differentiated thyroid carcinoma in childhood. Long term follow-up of 72 patients. J Clin Endocrinol Metab 65:1088
433a. Ali N, Sebastian C, Foley RR, Murray I, Canizales AL, Jenkins PJ, Drake WM, Plowman PN, Besser GM, Chew SL, Grossman AB, Monson JP, Britton KE. The management of differentiated thyroid cancer using 123I for imaging to assess the need for 131I therapy. Nucl Med Commun. 2006 Feb;27(2):165-9.
434. Cady, B, Sedgwick, C, Meissner, W, Bookwalter, J, Romagosa, V, Werber, J 1976. Changing clinical; pathologic; therapeutic; and survival patterns of differentiated thyroid carcinoma. Ann Surg 184:541
435. Mazzaferri, E, Young, R, Oertel, J, Kemmerer, W, Page, C 1977. Papillary thyroid carcinoma. The impact of therapy in 576 patients. Medicine 56:171
436. Mazzaferri, E, Young, R 1981. Papillary thyroid carcinoma. A ten year follow-up report of the impact of therapy in 576 patients. Am J Med 70:511
438. Samaan, N, Schultz, P, Hickey, R, et al. 1992. The results of various modalities of treatment of well differentiated thyroid carcinoma. A retrospective review of 1599 patients. J Clin Endocrinol Metab 75:714-720
438.1 Mazzaferri EL. Management of low-risk differentiated thyroid cancer. Endocr Pract. 2007 Sep-Oct;13(5):498-512
438.2 Hay ID. Management of patients with low-risk papillary thyroid carcinoma. Endocr Pract. 2007 Sep-Oct;13(5):521-33
438.3 Hay ID, Hutchinson ME, Gonzalez-Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goellner JR.Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period.Surgery. 2008 Dec;144(6):980-7
439. DeGroot, L, Reilly, M 1982. Comparison of 30- and 50-mCi doses of iodine-131 for thyroid ablation. Ann Intern Med 96:51
440. Roos, D e a 1999. Review of trials assessing low dose radioactive iodine ablation for thyroid remnants in patients with thyroid cancer. International J Rad Oncol Biol Physiol 44:493-495. 1.
440.1 Hackshaw A, Harmer C, Mallick U, Haq M, Franklyn JA. 131I Activity for Remnant Ablation Ablation in Patients with Differentiated Thyroid Cancer: A Systematic Review.J Clin Endocrinol Metab. 2007 Jan;92(1):28-38.
440.2 Pilli T, Brianzoni E, Capoccetti F, Castagna MG, Fattori S, Poggiu A, Rossi G, Ferretti F, Guarino E, Burroni L, Vattimo A, Cipri C, Pacini F. A Comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-Iodine Administered Doses for Recombinant Thyrotropin-Stimulated Postoperative Thyroid Remnant Ablation in Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2007 Sep;92(9):3542-6
440.4 Van Nostrand D, Aiken M, Atkins F, Moreau S, Garcia C, Acio E, Burman K, Wartofsky L. The Utility of Radioiodine Scans Prior to (131)I Ablation in Patients with Well-Differentiated Thyroid Cancer. Thyroid. 2009 Mar 13.
440a. Torlontano M , Crocetti U , Augello G , D’Aloiso L , Bonfitto N , Varraso A , Dicembrino F , Modoni S , Frusciante V , Di Giorgio A , Bruno R , Filetti S , Trischitta V . Comparative Evaluation of Recombinant Human Thyrotropin-Stimulated Thyroglobulin Levels, 131I Whole-Body Scintigraphy, and Neck Ultrasonography in the Follow-Up of Patients with Papillary Thyroid Microcarcinoma Who Have Not Undergone Radioiodine Therapy. J Clin Endocrinol Metab. 2006 Jan;91(1):60-3.
440b. Czepczynski R , Ziemnicka K , Baczyk M , Oleksa R , Ruchala M , Sowinski J . Fractionated dosage of radioiodine for the ablation of differentiated thyroid carcinoma. Thyroid. 2005 Nov;15(11):1261-5.
440c. Nucl Med Commun. 2003 May;24(5):489-95. Influence of diagnostic and therapeutic doses on thyroid remnant ablation rates. Karam M, Gianoukakis A, Feustel PJ, Cheema A, Postal ES, Cooper JA.
441. Wartofsky, L, Sherman, S, Gopal, J, Schlumberger, M, Hay, I 1998. The use of radioactive iodine in patients with papillary and follicular thyroid cancer. J Clin Endocrinol Metab 83:4195-4203
442. Caplan, R, Abellera, R, Kisken, W 1994. Hurthle cell neoplasms of the thyroid gland. Reassessment of functional capacity. Thyroid 4:243
423. Carcangiu, M, Bianchi, S, Savino, D, Voynick, I, Rosai, J 1991. Follicular Hurthle cell tumors of the thyroid gland. Cancer 68:1944-1953
444. Pacini, F, Molinaro, E, Castagna, M G, et al. 2002 Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal. J Clin Endocrinol Metab 87:4063-8
445. Robbins, R J, Tuttle, R M, Sonenberg, M, et al. 2001 Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin. Thyroid 11:865-9
445a. Kuijt WJ, Huang SA.; Children with Differentiated Thyroid Cancer Achieve Adequate Hyperthyrotropinemia within 14 Days of Levothyroxine Withdrawal. J Clin Endocrinol Metab. 2005 Aug 9
446. Guimaraes, V, DeGroot, L 1996. Moderate hypothyroidism in preparation for whole body 131I scintiscans and thyroglobulin testing. Thyroid 6:69-73
447. Schlumberger, M 1998. Papillary and follicular thyroid carcinoma. N Engl J Med 338:.297-306
448. Dow, K, Ferrell, B, Anello, C 1997. Quality of life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy. Thyroid 7:613-619
449. Ramirez, L, Braverman, L, White, B, Emerson, C 1997. Recombinant human thyrotropin is a potent stimulator of thyroid function in normal subjects. J Clin Endocrinol Metab 82:2836-2839
450. Meier, C, Braverman, L, Ebner, S, et al. 1994. Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (phase I/II study). J Clin Endocrinol Metab; 78:188-96
451. Ladenson, P, Braverman, L, Mazzaferri, E, al., e 1997. Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med 337:888-95
452. Haugen, B, Pacini, F, Reiners, C, et al. 1999. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 84:3877-3885
452.1 Driedger, AA; Kotowycz, N. Two cases of thyroid carcinoma that were not stimulated by recombinant human thyrotropin. J Clin Endocrinol Metab 89 585-590 2004.
452.2 Hänscheid H, Lassmann M, Luster M, Thomas SR, Pacini F, Ceccarelli C, Ladenson PW, Wahl RL, Schlumberger M, Ricard M, Driedger A, Kloos RT, Sherman SI, Haugen BR, Carriere V, Corone C, Reiners C.Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal.J Nucl Med. 2006 Apr;47(4):648-54
452.3 Pacini F, Molinaro E, Castagna MG, Lippi F, Ceccarelli C, Agate L, Elisei R, Pinchera A.Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal.J Clin Endocrinol Metab. 2002 Sep;87(9):4063-8
452.4 Berg G, Andersson T, Sjodell L, Jansson S, Nystrom E. Development of severe thyroid-associated ophthalmopathy in a patient with disseminated thyroid cancer treated with recombinant human thyrotropin/radioiodine and retinoic acid.Thyroid. 2005 Dec;15(12):1389-94
452a. Sorvillo, F; Mazziotti,G; Carbone, A; Piscopo, M; Rotondi, M; Cioffi, M; Musto, P; Biondi, B; Iorio, S; Amato, G; Carella, C. Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue. J Clin Endocrinol Metab 88 4818-4822 2003.
452b Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review.Endocr Relat Cancer. 2005 Mar;12(1):49-64.
453. Bachelot, A, Cailleux, A F, Klain, M, et al. 2002 Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma. Thyroid 12:707-11
454.Pacini, F, Capezzone, M, Elisei, R, Ceccarelli, C, Taddei, D, Pinchera, A 2002 Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab 87:1499-501
455. Pacini F, Molinaro E, Lippi F, Castagna MG, Agate L, Ceccarelli C, Taddei D, Elisei R, Capezzone M, and Pinchera A. Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab 86:5686-5690, 2001
455a. Phan HT , Jager PL , van der Wal JE , Sluiter WJ , Plukker JT , Dierckx RA , Wolffenbuttel BH , Links TP . The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol. 2008 Jan;158(1):77-83 : Eur J Endocrinol. 2008 Jan;158(1):77-83.
455b. Castagna MG , Brilli L , Pilli T , Montanaro A , Cipri C , Fioravanti C , Sestini F , Capezzone M , Pacini F . Limited value of repeat recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin testing in differentiated thyroid carcinoma patients with previous negative rhTSH-stimulated thyroglobulin and undetectable basal serum thyroglobulin levels. J Clin Endocrinol Metab. 2008 Jan;93(1):76-81
456. Mazzaferri, E, Kloos, R 2002. Is diagnostic Iodine-131 scanning with recombinant human TSH useful in the follow-up of differentiated thyroid cancer after thyroid ablation? J Clin Endocrinol Metab 87:1490-1498
457. Wartofsky, L 2002. Using baseline and recombinant human TSH-stimulated tg measurements to manage thyroid cancer without diagnostic 131I scanning. J Clin Endocrinol Metab 87:1486-1489
458.Wartofsky, L 2002 Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin. Thyroid 12:583-90
459a Pacini F, Schlumberger M, Harmer C, Berg GG, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Reiners C, Sanchez Franco F, Smit J, Wiersinga W. Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report Eur J Endocrinol. 2005 Nov;153(5):651-9.
459b.David A, Blotta A, Rossi R, Zatelli MC, Bondanelli M, Roti E, Braverman LE, Busutti L, degli Uberti EC. Clinical value of different responses of serum thyroglobulin to recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma. Thyroid. 2005 Mar;15(3):267-73. –
459c. Bachelot A, Leboulleux S, Baudin E, Hartl DM, Caillou B, Travagli JP,Schlumberger M. Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total body scan are not reliable criteria for cure after radioiodine treatment. Clin Endocrinol (Oxf). 2005 Mar;62(3):376-9.
459d. Smallridge RC, Meek SE, Morgan MA, Gates GS, Fox TP, Grebe S, Fatourechi V. Monitoring Thyroglobulin in a Sensitive Immunoassay Has Comparable Sensitivity to Recombinant Human TSH-Stimulated Thyroglobulin in Follow-Up of Thyroid Cancer Patients. J Clin Endocrinol Metab. 2007 Jan;92(1):82-7.
462.Lippi, F, Capezzone, M, Angelini, F, et al. 2001 Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH. Eur J Endocrinol 144:5-11
463. Galloway, R, Smallridge, R 1996. Imaging in thyroid cancer. Endocrinol Metab Clinics North America 25:93-113
464. Park, H-M, Perkins, O, Edmondson, J, Schnute, R, Manatunga, A 1994. Influence of diagnostic radioiodines on the uptake of ablative dose of Iodine-131. Thyroid 4:49
464a. Lassmann,M Luster M, Hanscheid H, Reiners C. Impact of 1313-I diagnostic Activities on the Biokinetics of Thyroid Remnants. J Nucl Med 45: 619-625, 2004.
465. Morris, L F, Waxman, A D, Braunstein, G D 2001 The nonimpact of thyroid stunning: remnant ablation rates in 131I-scanned and nonscanned individuals. J Clin Endocrinol Metab 86:3507-11
465a. Nucl Med Commun. 2004 Aug;25(8):799-805. Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy. Haq MS, McCready RV, Harmer CL.)(J Nucl Med. 2003
465b. Dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer: largest safe dose using a risk-adapted approach. Dorn R, Kopp J, Vogt H, Heidenreich P, Carroll RG, Gulec SA.)
465.1. Cailleux, A, Baudin, E, Travagli, J, Ricard, M, Schlumberger, M 2000. Is diagnostic Iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer? J Clin Endocrinol Metab 85:175-178
465.2. Van Nostrand, D, Atkins, F, Yeganeh, F, Acio, E, Bursaw, R, Wartofsky, L 2002. Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. Thyroid 12:121-134
465.3. O’Connell, M, Flower, M, Hinton, P, Harmer, C, McCready, V 1993. Radiation dose assessment in radioiodine therapy. Dose-response relationships in differentiated thyroid carcinoma using quantitative scanning and PET. Radiotherapy-Oncology 28:16-26
465.31 Tuttle RM , Leboeuf R , Robbins RJ , Qualey R , Pentlow K , Larson SM , Chan CY . Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer. J Nucl Med. 2006 Oct;47(10):1587-91.
465.4. Maxon, H, Thomas, S, Hertzberg, V, et al. 1983. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med 309:937
465.5. Koong, S-S, Reynolds, J, Movius, E, et al. 1999. Lithium as a potential adjuvant to 131I therapy of metastatic; well differentiated thyroid carcinoma. J Clin Endocrinol Metab 84:912-916
465.6. Carcangiu, M, Bianchi, S, Savino, D, Voynick, I, Rosai, J 1991. Follicular Hurthle cell tumors of the thyroid gland. Cancer 68:1944-1953
465.7. Fatourechi, V, Hay, I, Mullan, B, et al. 2000. Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer? Thyroid 10:573
465.8. Pelikan, D, Lion, H, Hermans, J, Goslings, B 1997. The role of radioactive iodine in the treatment of advanced differentiated thyroid carcinoma. Clin Endocrinol 47:713-720
465.9. Menzel, C, Grunwald, F, Schomburg, A, et al. 1996. “High-dose” radioiodine therapy in advanced differentiated thyroid carcinoma. J Nucl Med 37:1496-1503
465.10. Taylor, T, Specker, B, Robbins, J, et al. 1998. Outcome after treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma. Ann Intern Med 129:622-627
465.11. Pittas, A, Adler, M, Fazzari, M, et al. 2000. Bone metastases from thyroid carcinoma. clinical characteristics and prognostic variables in one hundred forty-six patients. Thyroid 10:261-268
465.12. Durante C , Haddy N , Baudin E , Leboulleux S , Hartl D , Travagli JP , Caillou B , Ricard M , Lumbroso JD , De Vathaire F , Schlumberger M Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006 Aug;91(8):2892-9.
467.Van Tol, K, Hew, J, Jager, P, Vermey, A, Dullaart, R, Links, T 2000. .Embolization in combination with radioiodine therapy for bone metastases from differentiated thyroid carcinoma. Clin Endocrinol 52:653-659
468. . Meier, C, Braverman, L, Ebner, S, et al. 1994. Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (phase I/II study). J Clin Endocrinol Metab; 78:188-96
469. Hamburger, J, Desai, P Mannitol augmentation of I131 uptake in the treatment of thyroid carcinoma. Metabolism 15 1055: 1966.
369a. Elisei, R; Vivaldi, A; Agate, L; Molinaro, E; Nencetti, C; Grasso, L; Pinchera, A; Pacini, F. Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents its use in the follow-up of differentiated thyroid cancer patients. J Clin Endocrinol Metab 89 29-32 2004.
470.Hamburger, J 1969. Diuretic augmentation of 131I uptake in inoperable thyroid cancer. N Engl J Med 280:1091
471. Pacini, F, Lippi, F, Formica, N, et al. 1987. Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med 28:1888
472.Schlumberger, M, Arcangioli, O, Piekarski, J, Tubiana, M, Parmentier, C 1988. Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays. J Nucl Med 29:1790-1794
473. Pineda, J, Lee, T, Ain, K, Reynolds, J, Robbins, J 1995. Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab 80:1488
474. McDougall, I 1997 131I treatment of 131I negative whole body scan; and positive thyroglobulin in differentiated thyroid carcinoma. what is being treated? Thyroid 7:669
475. Wartofsky, L, Sherman, S, Gopal, J, Schlumberger, M, Hay, I 1998. The use of radioactive iodine in patients with papillary and follicular thyroid cancer. J Clin Endocrinol Metab 83:4195-4203
476. Fatourechi, V, Hay, I D, Javedan, H, Wiseman, G A, Mullan, B P, Gorman, C A 2002 Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer. J Clin Endocrinol Metab 87:1521-6
476a. Alzahrani AS, Mohamed G, Al Shammary A, Aldasouqi S, Abdal Salam S, Shoukri M Long-term course and predictive factors of elevated serum thyroglobulin and negative diagnostic radioiodine whole body scan in differentiated thyroid cancer. J Endocrinol Invest. 2005 Jun;28(6):540-6.
476.1 Koh J-M, Kim ES, Ryu JS, Hong SJ, Kim WB, Shong YK. Effects of therapeutic doses of 131I in thyroid papillary carcinoma patients with elevated thyroglobulin level and negative 131I whole-body scan: comparative study. Clin Endocrinol 58:421-427, 2003.
477. Maxon, H, Thomas, S, Hertzberg, V, et al. 1983. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med 309:937
478. Benua, R, Cicale, N, Sonenberg, M, Rawson, R 1971 The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer. Am J Roentgenol Rad Ther Nucl Med: 87
479. Van Nostrand, D, Atkins, F, Yeganeh, F, Acio, E, Bursaw, R, Wartofsky, L 2002. Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. Thyroid 12:121-134
480.Grigsby, P, Siegel, B, Baker, S, Eichling, J 2000. Radiation exposure from outpatient radioactive iodine (131I) therapy for thyroid carcinoma. J Amer Med Assn 283:2272-2274
482. Seidlin, S, Yalow, R, Siegel, E 1952. Blood radioiodine concentration and blood radiation dosage during I131 therapy for metastatic thyroid carcinoma. J Clin Endocrinol Metab 12:1197
482b. Kim SJ, Choi HY, Kim IJ, Kim YK, Jun S, Nam HY, Kim JS.Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan.Thyroid. 2008 Mar;18(3):325-31
482.1 Mandel SJ, Mandel L. Radioactive iodine and the salivary glands. Thyroid 13:265-271, 2003.Guma M, Salinas I, Reverter JL, Roca J, Valls-Roc M, Juan M, Olive A. Frequency of antineutrophil cytoplasmic antibody in Graves’ disease patients treated with methimazole. J Clin Endocrinol Metab 88:2141-2146, 2003.
482a. Nakada K, Ishibashi T, Takei T, Hirata K, Shinohara K, Katoh S, Zhao S, Tamaki N, Noguchi Y, Noguchi S.Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer? J Nucl Med. 2005 Feb;46(2):261-6.
483. Raymond, J, Izembart, M, Marliac, V, et al. 1989. Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine. J Clin Endocrinol Metab 69:186
484. Pacini, F, Gasperi, M, Fugazzola, L, et al. 1994. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine. J Nucl Med 35:1418
485. Ceccarelli, C, Battisti, P, Gasperi, M, et al. 1999. Radiation dose to the testes after 131I therapy for ablation of postsurgical thyroid remnants in patients with differentiated thyroid cancer. J Nucl Med 40:1716
485a. Rosario PW, Barroso AL, Rezende LL, Padrao EL, Borges MA, Guimaraes VC, Purisch S. Testicular function after radioiodine therapy in patients with thyroid cancer.Thyroid. 2006 Jul;16(7):667-70
486. Pochin, E 1960. Leukemia following radioiodine treatment of thyrotoxicosis. Br Med J 2:1545
487. Wiseman, J, Hales, I, Joasoo, A 1982. Two cases of lymphoma of the parotid gland following ablative radioiodine therapy for thyroid carcinoma. Clin Endocrinol 17:85
488. Rall, J, Alpers, J, Lewallen, C, Sonenberg, M, Berman, M, Rawson, R 1957. Radiation pneumonitis and fibrosis. A complication of I131 treatment of pulmonary metastases from cancer of the thyroid. J Clin Endocrinol Metab 17:1263
489. Exelby, P, Frazell, E 1969. Carcinoma of the thyroid in children. Surg Clin North Am 49:249
491. Trunnell, J, Marinelli, L, Duffy, B J, Hill, R, Peacock, W, Rawson, R 1949. The treatment of metastatic thyroid cancer with radioactive iodine. Credits and debits. J Clin Endocrinol Metab 19:1138
492. Lin, J, Wang, H, Weng, H, Kao, P 1998. Outcome of pregnancy after radioactive iodine treatment for well differentiated thyroid carcinomas. J Endocrinol Invest 21:662-667
492a. . Bal C, Kumar A, Tripathi M, Chandrashekar N, Phom H, Murali NR, Chandra P, Pant S.; High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring. Int J Radiat Oncol Biol Phys. 2005 Aug 9
493.Schlumberger, M, De Vathaire, F, Ceccarelli, C, et al. 1996. Exposure to radioactive iodine-131 for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients. J Nucl Med 37:606
494.. Trunnell, J, Marinelli, L, Duffy, B J, Hill, R, Peacock, W, Rawson, R 1949. The treatment of metastatic thyroid cancer with radioactive iodine. Credits and debits. J Clin Endocrinol Metab 19:1138
495. Lin, J, Wang, H, Weng, H, Kao, P 1998. Outcome of pregnancy after radioactive iodine treatment for well differentiated thyroid carcinomas. J Endocrinol Invest 21:662-667
496. Varma, V, Beierwaltes, W, Nofal, M, Nishiyama, R, Copp, J 1437 Treatment of thyroid cancer. Death rates after surgery and after surgery followed by sodium iodide. I131 JAMA: 214
497. Leeper, R 1973. The effect of 131I therapy on survival of patients with metastatic papillary or follicular thyroid carcinoma. J Clin Endocrinol Metab 36:1143
498. Mazzaferri, E, Young, R 1981. Papillary thyroid carcinoma. A ten year follow-up report of the impact of therapy in 576 patients. Am J Med 70:511
499. see 496
500. see 497
501. Marcocci, C, Pacini, F, Elisei, R, et al. 1989. Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma. Surgery 106:960
502.O’Connell, M, Flower, M, Hinton, P, Harmer, C, McCready, V 1993. Radiation dose assessment in radioiodine therapy. Dose-response relationships in differentiated thyroid carcinoma using quantitative scanning and PET. Radiotherapy-Oncology 28:16-26
503. Rall, J, Alpers, J, Lewallen, C, Sonenberg, M, Berman, M, Rawson, R 1957. Radiation pneumonitis and fibrosis. A complication of I131 treatment of pulmonary metastases from cancer of the thyroid. J Clin Endocrinol Metab 17:1263
504. Exelby, P, Frazell, E 1969. Carcinoma of the thyroid in children. Surg Clin North Am 49:249
505. Lin, J, Wang, H, Weng, H, Kao, P 1998. Outcome of pregnancy after radioactive iodine treatment for well differentiated thyroid carcinomas. J Endocrinol Invest 21:662-667
506. Saenger, E, Barrett, C, Passino, J, Seltzer, R, Dooley, W 1964. Experiences with I131 in the management of carcinoma of the thyroid. Radiology 83:892
507. Varma, V, Beierwaltes, W, Nofal, M, Nishiyama, R, Copp, J 1437 Treatment of thyroid cancer. Death rates after surgery and after surgery followed by sodium iodide. I131 JAMA: 214
508. Marcocci, C, Pacini, F, Elisei, R, et al. 1989. Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma. Surgery 106:960
509. Harness, J, Thompson, N, Sisson, J, Beierwaltes, W 1974. Differentiated thyroid carcinomas. Treatment of distant metastases. Arch Surg 108:410
510. Solomon, B, Wartofsky, L, Burman, K 1996. Current trends in the management of well differentiated papillary thyroid carcinoma. J Clin Endocrinol Metab 81:333-339
511.Shands, W, Gatling, R 1970. Cancer of the thyroid. Review of 109 cases. Ann Surg 171:735
512. Solomon, B, Wartofsky, L, Burman, K 1996. Current trends in the management of well differentiated papillary thyroid carcinoma. J Clin Endocrinol Metab 81:333-339
513. Schlumberger, M 1998. Papillary and follicular thyroid carcinoma. N Engl J Med 338:.297-306
514. Sherman, S, Tielens, E, Sostre, S, Wharam, M J, Ladenson, P 1994. Clinical utility of post-treatment radioiodine scans in the management of patients with thyroid cancer. J Clin Endocrinol Metab 78:629
514.1 Hovens GC, Stokkel MP, Kievit J, Corssmit EP, Pereira AM, Romijn JA, Smit JW. Associations of serum thyrotropin concentrations with recurrence and death in differentiated thyroid cancer. J Clin Endocrinol Metab. 2007 Jul;92(7):2610-5.
515. Charles, M, Dodson, L, Waldeck, N, et al. 1980. Serum thyroglobulin levels predict total body iodine scan findings in patients with treated well-differentiated thyroid carcinoma. Am J Med 69:401
516. Pacini, F, Pinchera, A, Giani, C, Grasso, L, Baschieri, L 1980. Serum thyroglobulin concentrations and 131-I whole body scans in the diagnosis of metastases from differentiated thyroid carcinoma (after thyroidectomy). Clin Endocrinol 13:107
517. Barsano, C, Skosey, C, DeGroot, L, Refetoff, S 1982. Serum thyroglobulin in the management of patients with thyroid cancer. Arch Intern Med 142:763
518. Pacini, F, Pinchera, A, Giani, C, Grasso, L, Doveri, F, Baschieri, L 1980. Serum thyroglobulin in thyroid carcinoma and other thyroid disorders. J Endocrinol Invest 3:283
519. Johansen, K, Woodhouse, N 1992. Comparison of thyroglobulin and radioiodine scintigraphy during follow-up of patients with differentiated thyroid carcinoma. Eur J Med 1:403-406
520. Cailleaux, A, Baudin, E, Travagli, J, Ricard, M, Schlumberger, M 2000. Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer? J Clin Endocrinol Metab 85:175
521. Capezzone, M, Sculli, M, Agate, L, Ceccarelli, C, Pacini, F 2000. Diagnostic 131-I whole body scan after total thyroidectomy and thyroid ablation is useless in thyroid cancer patients with undetectable serum thyroglobulin off l-thyroxine therapy. J Endocrinol Invest (Suppl) 23:3
522. Haugen, B, Pacini, F, Reiners, C, et al. 1999. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 84:3877-3885
523. Sisson, J, Thompson, N, Giordano, T, England, B, Normolle, D 2000. Serum thyroglobulin levels after thyroxine withdrawal in patients with low risk papillary thyroid carcinoma. Thyroid 10:165
523a. Chiovato, L; Latrofa, F; Braverman, LE; Pacini, F; Capezzone, M; Masserini, L; Grasso, L; Pinchera, A. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med 139 346-351 2003.
524. Fugazzola, L, Mihalich, A, Persani, L, et al. 2002 Highly sensitive serum thyroglobulin and circulating thyroglobulin mRNA evaluations in the management of patients with differentiated thyroid cancer in apparent remission. J Clin Endocrinol Metab 87:3201-8
525. Pujol, P, Daures, J-P, Nsakala, N, Baldet, L, Bringer, J, Jaffiol, C 1996. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab 81:4318-4323
526. Cooper, D, Specker, B, Ho, M, et al. 1998 Thyroid 8: 737
527.Marcocci, C, Golia, F, Bruno-Bossio, G, Vignali, E, Pinchera, A 1994. Carefully monitored lecothyroxine suppressive therapy is not associated with bone loss in premenopausal women. . J Clin Endocrinol Metab 78:818-23
528. Kim, J, Leeper, R 1983. Treatment of anaplastic and spindle cell carcinoma of the thyroid gland with combination adriamycin and radiation therapy. Cancer 52:954
528a. Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1137-43 ,Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy,and hyperfractionated accelerated external radiotherapy. De Crevoisier R, Baudin E, Bachelot A, Leboulleux S, Travagli JP, Caillou B,Schlumberger M.
529. Ain, K 1998. Anaplastic thyroid carcinoma. Behavior; biology; and therapeutic approaches. Thyroid 8:715
530. Butler, J, Brady, L, Amendola, B 1990. Lymphoma of the thyroid. Report of five cases and review. Amer J Clin Oncol (CCT) 13:64
531. Souhami, L, Simpson, W, Carrothers, J 1980. Malignant lymphoma of the thyroid gland. Int J Radiat Oncol Biol Phys 6:1143
532. Grimley, R, Oates, G 1980. The natural history of malignant thyroid lymphomas. Br J Surg 67:475
533.Leedman, P, Sheridan, W, Downey, W, Fox, R, Martin, F 1990. Combination chemotherapy as single modality therapy for stage IE and IIE thyroid lymphoma. Med J Australia 152:40
534.Chak, L, Hoppe, R, Burke, J, Kaplan, H 1981. Non- Hodgkin’s lymphoma presenting as thyroid enlargement. Cancer 48:2712
535.Matsuzuka, F, Miyauchi, A, Katayama, S, et al. 1993. Clinical aspects of primary thyroid lymphoma. Diagnosis and treatment based on our experience of 119 cases. Thyroid 3:93-99
536. Tubiana, M 1981. External radiotherapy and radioiodine in the treatment of thyroid cancer. World J Surg 5:75
537. Simpson, W 1975. Radiotherapy in thyroid cancer. Can Med Assoc J 113:115
538. Riccabona, G 1979. Radiotherapy and nuclear medicine in malignant tumors of the thyroid gland. Therapiewoche 29:3448
539. Tubiana, M, Lacour, J, Monnier, J, et al. 1975. External radiotherapy and radioiodine in the treatment of 359 thyroid cancers. Br J Radiol 48:894
540. Brierley, J, Tsang, R 1996. External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clinics North America 25:141-157
541. Lin, J-D, Tsang, N-M, Huang, M-J, Weng, H-F 1997. Results of external beam radiotherapy in patients with well differentiated thyroid carcinoma. Jpn J Clin Oncol 27:244-247
542. Farahati, J, Reiners, C, Stuschke, M, et al. 1996. Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (Stage pT4). Cancer 77:172-179
543.Tsang, R, Brierley, J, Simpson, W, Panzarella, T, Gospodarowicz, M, Sutcliffe, S 1998. The effects of surgery; radioiodine; and external radiation therapy on the clinical outcome of patients with differentiated thyroid carcinoma. Cancer 82:375-387
543a. Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):1067-72. Is there a role for radiation therapy in the management of Hurthle cell carcinoma? Foote RL, Brown PD, Garces YI, McIver B, Kasperbauer JL.
544 . Harada, T, Nishikawa, Y, Suzuki, T, Ito, K, Baba, S 1971. Bleomycin treatment for cancer of the thyroid. Am J Surg 122:53
545. Gottlieb, J, Hill, C, Ibanez, M, Clark, R 1972. Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30:848
546. Jereb, B, Stjernsward, J, Lowhagen, T 1975. Anaplastic giant-cell carcinoma of the thyroid. Cancer 35:1293
547. Shimaoka, K, Reyes, J American Elsevier Chemotherapy of thyroid carcinoma. in Robbins, J; Braverman, L (eds). Thyroid Research: New York
549. Riccabona, G, Zechmann, W, Fill, H American Elsevier Cytostatic drug therapy of thyroid cancer. in Robbins, J; Braverman, L (eds) Thyroid Research: New York
550. De Besi, P, Busnardo, B, Toso, S, et al. 1991. Combined chemotherapy with bleomycin; adriamycin; and platinum in advanced thyroid cancer. J Endocrinol Invest 14:475
551. Committee, C, Surgery., T J S o T 1995. Intensive chemotherapy for anaplastic thyroid carcinoma. combination of cisplatin; doxorubicin; etoposide; and peplomycin with granulocyte colony-stimulating factor support. Jpn J Clin Oncol 25:203-207
552 Ain, K, Egorin, M, DeSimone, P 2000. Treatment of anaplastic thyroid carcinoma with Paclitaxel. phase 2 trial using ninety-six hour infusion. Thyroid 10:587
553. Busnardo, B, Daniele, O, Pelizzo, M, et al. 2000. A multimodality therapeutic approach in anaplastic thyroid carcinoma. Study on 39 patients. J Endocrinol Invest 23:755-761
553a. Gilliam LK , Kohn AD , Lalani T , Swanson PE , Vasko V , Patel A , Livingston RB , Pickett CA . Capecitabine therapy for refractory metastatic thyroid carcinoma: a case series. Thyroid. 2006 Aug;16(8):801-10.
554. Santini, F, Bottici, V, Elisei, R, et al. 2002 Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab 87:4160-5
554.1 de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ, Voest EEA Phase II Trial of Imatinib Therapy for Metastatic Medullary Thyroid Carcinoma. J Clin Endocrinol Metab. 2007 Sep;92(9):3466-9
554.2 Pennell NA, Daniels GH, Haddad RI, Ross DS, Evans T, Wirth LJ, Fidias PH, Temel JS, Gurubhagavatula S, Heist RS, Clark JR, Lynch TJ A Phase II Study of Gefitinib in Patients with Advanced Thyroid Cancer. Thyroid. 2008 Mar;18(3):317-23
554.3 Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ; Motesanib Thyroid Cancer Study Group. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008 Jul 3;359(1):31-42.
554.4 Kloss RT, Ringel MD, Knopp MV, et all:Phase II trial of sorafenib in metastatic thyroid cancer J Clin Oncol. 27:1675-84. 2009
554.5 Waguespack SG, Sherman SI, Williams MD, Clayman GL, Herzog CE. The successful use of sorafenib to treat pediatric papillary thyroid carcinoma. Thyroid. 2009 Apr;19(4):407-12.
554.6 Dawson SJ, Conus NM, Toner GC, Raleigh JM, Hicks RJ, McArthur G, Rischin D Sustained clinical responses to tyrosine kinase inhibitor sunitinib in thyroid carcinoma. . Anticancer Drugs. 2008 Jun;19(5):547-52.
554.7 Morabito A, Piccirillo MC, Falasconi F, De Feo G, Del Giudice A, Bryce J, Di Maio M, De Maio E, Normanno N, Perrone F. Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. Oncologist. 2009 Apr;14(4):378-90.
554.8 Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008 Oct 10;26(29):4708-13.
555. Simon, D, Koehrle, J, Reiners, C, et al. 1998. Redifferentiation therapy with retinoids. therapeutic option for advanced follicular and papillary thyroid carcinoma. World J Surg 22:569-574
555a. Furuya, F; Shimura, H; Suzuki, H; Taki, K; Ohta, K; Haraguchi, K; Onaya, T; Endo, T; Kobayashi, T. Histone deacetylase inhibitors restore radioiodine uptake and retention in poorly differentiated and anaplastic thyroid cancer cells by expression of the sodium/iodide symporter thyroperoxidase and thyroglobulin. Endocrinology 2004.
555b. Fortunati, N; Catalano, MG; Arena, K; Brignardello, E; Piovesan, A; Boccuzzi, G. Valproic acid induces the expression of the Na+/I- symporter and iodine uptake in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab 89 1006-1009 2004.
556. Schmutzler, C, Kohrle, J 2000. Retinoic acid redifferentiation therapy for thyroid cancer. Thyroid 10:393-406
557. Martelli, M L, Iuliano, R, Le Pera, I, et al. 2002 Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth. J Clin Endocrinol Metab 87:4728-35
558. Portella, G, Scala, S, Vitagliano, D, Vecchio, G, Fusco, A 2002 ONYX-015, an E1B gene-defective adenovirus, induces cell death in human anaplastic thyroid carcinoma cell lines. J Clin Endocrinol Metab 87:2525-31
561. Tanaka, K; Towata, S; Nakao, K; Mizuguchi, H; Hayakawa, T; Niwa, M; Ishii, N; Nagayama, Y. Thyroid cancer immunotherapy with retroviral and adenoviral vectors expressing granulocyte macrophage colony stimulating factor and interleukin-12 in a rat model. Clin Endocrinol 59 734-742 2003.
562. Schuck, A; Biermann, M; Pixberg, MK; Muller, SB; Heinecke, A; Schober, O; Willich, N. Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma. First results of the multicnter study on differentiated thyroid carcinoma (MSDS). Strahlenther Onkol 179 832-839 2003.
563. Schoenberger, J; Grimm, D; Kossmehl, P; Infanger, M; Kurth, E; Eilles, C. Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study. Endocrinology 145 1031-1038 2004.
564.Braga-Basaria, M; Ringel, MD. Beyond radioiodine: A review of potential new therapeutic approaches for thyroid cancer. J Clin Endocrinol Metab 88 1947-1960 2003.