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 (71). These may be regarded as atypical subacute thyroiditis patients but their natural history of the disease is not known. When the symptom is difficulty in swallowing, the disorder may be initially mistaken for pharyngitis. At times, the pain begins in one pole and then spreads rapidly to involve the rest of the gland ("creeping thyroiditis"). It 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 causes temperatures to rise daily above 104oF (40.0oC). 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 (72,73).

Approximately one-half of the patients present during the first weeks of the illness, with symptoms of thyrotoxicosis, including nervousness, heat intolerance, palpitations, tremulousness, and increased sweating. These symptoms are caused by excessive release of thyroid hormone from the thyroid gland during the acute phase of the inflammatory process. 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 (24,25,42). Occasionally the condition may be painless and present as fever of unknown origin (74).

Table 19-1 provides a comparison between the clinical and laboratory findings of patients with subacute and acute thyroiditis (25,75-80). Laboratory examination may disclose a moderate leukocytosis. A curious and striking elevation of the erythrocyte sedimentation rate, at times above 100 mm/hr, or serum C-reactive protein (81) is a useful diagnostic clue. Short of 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, and an absent or low titer of circulating TG antibodies. While the estimation of thyrotropin receptor antibodies (TRAb) in a thyrotoxic patient may be clinically useful in Graves' disease there have been reports of positive TRAb in patients with subacute thyroiditis although the frequency of positivity is low (82-84, 90). Mild anemia and hyperglobulinemia may be present. The value of a 99m-Tc-pertechnetate scintigraphy as a marker of disease actviity and severity has been noted (85). Further imaging studies have shown diffuse increased uptake of Tc-99m sestamibi in the thyroid region of patients in the acute phase (thyrotoxic) of subacute thyroiditis suggesting increased perfusion; at the same time Tc-99m pertechnetate uptake was markedly reduced. It is possible that Tc-99m sestamibi uptake in the early phase may reflect the inflammatory process associated with the disease (86). 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 emphasised (87) Subacute thyroiditis with thyrotoxicosis may also be distinguished from Graves' hyperthyroidism by using T1- and T2- diffusion weighted magnetic resonance imaging (87) although this investigation may not be available or even desirable in all centres. 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 (87a).

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.

Figure 19-3 (below) shows a sequence of 125I and 241Am 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 m g/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 reaccumulation 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.

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 will demonstrate failure of the involved areas of the gland to concentrate iodide. 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 nonhydrolyzed iodoproteins from the inflamed tissue, the serum T3 level is also high. During this phase the serum TSH level is low, and the TSH response to TRH is suppressed (76) 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 (78). At this time, the involved tissue shows decreased but not necessarily depleted stores of iodine, as determined by x-ray fluorescence (75,78). Administration of TSH usually fails 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 in the hyperthyroid phase probably reflect the short duration of exposure to increased thyroid hormone (89).

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. 19-4). Restoration of iodine stores appears to be much slower and may take more than a year after the complete clinical remission (75,8). 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 (51).

Diagnosis is usually not difficult. With an acutely enlarged, tender thyroid, an RAIU near zero, and elevated serum T4 and Tg concentrations and ESR, the diagnosis is almost certain. Circulating thyroid autoantibodies are absent or the titer is low. Among the diagnostic alternatives, infectious thyroiditis must be considered and the possibility of invading bacteria excluded (see Table 19-1). The thyroid in Hashimoto's thyroiditis may be slightly tender and painful, but this event is rare, and the typical disturbances in iodine metabolism and erythrocyte sedimentation rate are not found. Hemorrhage into a cyst in a nodular thyroid gland may be confused with subacute thyroiditis. 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 iodine. This event occurs particularly in transient thyrotoxicosis induced by iodine (79). 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 (80). 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 typically painless, and there are no associated systemic symptoms. This condition has been formerly confused with subacute (deQuervain's) thyroiditis, whence come the misleading terms silent, painless, or atypical subacute thyroiditis. 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 be very suggestive of thyroid cancer. Usually the degree of pain and tenderness, elevated erythrocyte sedimentation rate and leukocytosis, and remission or spread to other parts of the gland make clinical differentiation possible. Gray-scale and color Doppler sonography may be helpful in this situation (87,91) but a fine needle aspiration is required for a definitive differentation between these two processes (91).

In some patients, 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, prednisone administration should be employed (24,42). 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 the problem as being due to 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) may be used safely and effectively for the management of hyperthyroidism in these patinents even when they have relapsed after corticosteroid therapy (93). 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 (94). Levothyroxine administration may be useful in situations where the patient is not already hyperthyroid due to the release of thyroidal contents into the circulation. It is thought that TSH suppression will reduce the thyroid stimulation which might otherwise prolong the inflammatory process. It is also necessary to administer thyroid hormones, at least transiently, if the patient enters a phase of hypothyroidism subsequent to the acute inflammation. TSH-suppressive doses of levothyroxine should only be administered when there is evidence that exacerbation of the condition occurs when TSH is present. Otherwise, the return of thyroid function to normal, which presumably is facilitated by TSH, can 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. This occurs prior to re-establishment of normal thyroid function and should not be confused with hyperthyroidism due to Graves' Disease. Surgical intervention is not the primary treatment for subacute thyroiditis. Experience from the Mayo clinic (95) has shown that if surgery is performed for a clinically indeterminate thyroid nodule resection is safe and with low morbidity.

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. It is of interest that elevated levels of serum Tg 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 (96).