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Among the several imaging techniques that provide clinically useful anatomic information about the thyroid gland, sonography has become the method that is most commonly employed. Indeed, the widespread use of ultrasonography has resulted in an epidemic of clinically inapparent thyroid nodules, the overwhelming majority of which are benign although some are cancers. The high sensitivity but poor specificity of the technique has posed a management and economic problem. Previously, imaging of the thyroid required scintiscanning to provide a map of those areas of the thyroid that accumulate and process radioactive iodine. Although, scintiscanning remains of primary importance in patients who are hyperthyroid or for detection of iodine-avid tissue after thyroidectomy for thyroid cancer, sonography has largely replaced it for the majority of patients who require a graphic representation of the regional anatomy because of its higher resolution, superior correlation of true thyroid dimensions with the image, smaller expense, greater simplicity, and lack of need for radioisotope administration. The other imaging methods, computerized tomography (CT) and magnetic resonance imaging (MRI) are more costly than sonography, are not as efficient in detecting small lesions, and are best used selectively when sonography is inadequate to elucidate a clinical problem. [1, 1A]
As with any test, sonography should be used to refine a differential diagnosis only when it is needed to answer a specific diagnostic question that has been raised by the clinical history and physical examination. [2] The image must then be integrated into patient management and correlated precisely with the other data. A technique has been reported that helps the clinician to interpret thyroid scintigrams of goiters and functioning nodules by assembling scintiscans and sonograms side-by-side as one composite image. [2A]
Although sonography can supply very important and clinically useful clues about the nature of a thyroid lesion, it does not reliably differentiate benign lesions and cancer. Rather, sonography can:
1. Depict accurately the anatomy of the neck in thyroid region,
2. Help the student and clinician to learn thyroid palpation,
3. Elucidate cryptic findings on physical examination,
4. Assess the comparative size of nodules, lymph nodes, or goiters in patients who are under observation or therapy,
5. Detect a non-palpable thyroid lesion in a patient who was exposed to therapeutic irradiation,
6. Give very important and clinically useful clues about the likelihood of malignancy,
7. Identify the solid component of a complex nodule,
8. Facilitate fine needle aspiration biopsy of a nodule,
9. Evaluate for recurrence of a thyroid mass after surgery,
10. Monitor thyroid cancer patients for early evidence of reappearance of malignancy in the thyroid bed or lymphadenopathy,
11. Identify patients who have ultrasonic thyroid patterns that suggest diagnoses such as thyroiditis.
12. Refine the management of patients on therapy such as antithyroid drugs,
13. Facilitate delivery of medication or physical high-energy therapy precisely into a lesion and spare the surrounding tissue,
14. Monitor in-utero the fetal thyroid for size, ultrasonic texture, and vascularity,
15. Scrutinize the neonatal thyroid for size and location,
16. Screen in the field the thyroid during epidemiologic investigation.
Sonography depicts the internal structure of the thyroid gland and the regional anatomy and pathology without using ionizing radiation or iodine containing contrast medium. [3,4] Rather, high frequency sound waves in the megahertz range (ultrasound), are used to produce an image. The procedure is safe, does not cause damage to tissue and is less costly than any other imaging procedure. The patient remains comfortable during the test, which takes only a few minutes, does not require discontinuation of any medication, or preparation of the patient. The procedure is usually done with the patient reclining with the neck hyperextended but it can be done in the seated position. A probe that contains a piezoelectric crystal called a transducer is applied to the neck but since air does not transmit ultrasound, it must be coupled to the skin with a liquid medium such a gel. This instrument rapidly alternates as the generator of the ultrasound and the receiver of the signal that has been reflected by internal tissues. The signal is organized electronically into numerous shades of gray and is processed electronically to produce an image instantaneously (real-time). Although each image is a static picture, rapid sequential frames are processed electronically to depict motion. Two-dimentional images have been standard and 3-dimentional images are an improvement in certain circumstances. [4A] There is considerable potential for improving ultrasound images of the thyroid by using ultrasound contrast agents. These experimental materials include gas-filled microbubbles with a mean diameter less than that of a red blood corpuscle and Levovist, an agent consisting of granules that are composed of 99.9% galactose and 0.1% palmitic acid. They are injected intravenously, enhance the echogenicity of the blood, and increase the signal to noise ratio. [5, 5A]
Dynamic information such as blood flow can be added to the signal by employing a physics principle called the Doppler effect. The Doppler signals, which are superimposed on real time gray scale images, are extremely bright in black and white images and may be color coded to reveal the velocity (frequency shift) and direction of blood flow (phase shift) as well as the degree of vascularity of an organ. [6,7] Flow in one direction is made red and in the opposite direction, blue. The shade and intensity of color can correlate with the velocity of flow. Thus, in general terms, venous and arterial flow can be depicted by assuming that flow in these two kinds of blood vessels is parallel, but in opposite directions. Since portions of blood vessels may be tortuous, modifying orientation to the probe, different colors are displayed within the same vessel even if the true direction of blood flow in that vessel has not changed. Thus, an analysis of flow characteristics requires careful observations and cautious interpretations. The absence of flow in a fluid-filled structure can differentiate a cystic structure and a blood vessel.
The ultrasound is treated differently by the various anatomic features and different kinds of tissues. [1,4] The air-filled trachea does not transmit the ultrasound. Calcified tissues such as bone and sometimes cartilage and calcific deposits in other anatomic structures block the passage of ultrasound resulting in a very bright signal and a linear echo-free shadow distally. Most tissues transmit the ultrasound to varying degrees and interfaces between tissues reflect portions of the sound waves. Fluid-filled structures have a uniform echo-free appearance whereas fleshy structures and organs have a ground glass appearance that may be uniform or heterogeneous depending on the characteristics of the structure.
The depth penetration and resolving power of ultrasound depends greatly on frequency. [3] Depth penetration is inversely related and spatial resolution is directly related to the frequency of the ultrasound. For thyroid, a frequency of 7.5 to 10 or 14 megahertz is generally optimal for all but the largest goiters. Using these frequencies, nodules as small as two to three millimeters can be identified.
Routine protocols for sonography are not adequate. Although some technologists become extremely proficient after specific training and experience, supervision and participation by a knowledgeable and interested physician-sonographer is usually required to obtain a precise and pertinent answer to a specific problem that has been posed by the clinician. Standard sonographic reports may provide considerable information about the anatomy, but are suboptimal unless the specific clinical concern is explored and answered. Indeed, because some radiologists cannot address the clinical issue adequately, and for convenience, numerous thyroidologists and a few surgeons perform their own ultrasound examinations, in which case it is essential that they have state-of-the-art equipment (that might not be cost-effective) and that they are willing to expend a considerable amount of time for a complete study. Technical ingenuity, electronic enhancements such as Doppler capability, and even artistry are frequently required. Special maneuvers, various degrees of hyperextension of the neck, swallowing to the facilitate elevation of the lower portions of the thyroid gland above the clavicles, swallowing water to identify the esophagus, and a Valsalva maneuver to distend the jugular veins may enhance the value of data. Nevertheless, sonography is rather difficult to interpret in the upper portion in of the jugular region and in the areas adjacent to the trachea. Sonography is generally not useful below the clavicles.
It is informative for orientation to survey the entire thyroid gland with a low-energy transducer before proceeding to 10-14 megahertz equipment to delineate the fine anatomy. Protocols have been devised to assemble a montage of images to encompass an unusually large lobe or goiter. For an overview, panoramic ultrasound, which is a variation of conventional ultrasound has been reported to produce images with a large anatomic field of view, displaying both lobes of the thyroid gland on a single image.[5B]
There may be considerable differences between sonologists in estimating the size of large goiters or nodules. One investigation has reported that curved-array transducers avoid significant inter-observer variation that may occur when linear-array equipment is employed, especially when the gland is enlarged. [5C] The inter-observer variation may be almost 50% among experienced ultrasonographers for the determination of the volume of thyroid nodules, because it is difficult to reproduce a two-dimensional image plane for multiple studies. [5D] Accuracy in volume estimation becomes most important when one uses ultrasound measurements to calculate an isotope dose or to compare changes over time in the size of a nodule or a goiter. Using planimetry from three-dimensional images reportedly has lower intra-observer variability (3.4%) and higher repeatability (96.5%) than the standard ellipsoid model for nodules and lobes, with 14.4% variability and 84.8% repeatability (p < 0.001). [5E]
There may be imperfect concordance between the ultrasonic dimensions of large thyroid nodules compared with surgical excision. [5F]
The anterior neck is depicted rather well with standard gray scale sonography. (FIGURE 1) The thyroid gland is slightly more echo-dense than the adjacent structures because of its iodine content. It has a homogenous ground glass appearance. Each lobe has a smooth globular-shaped contour and is no more than 3 - 4 centimeters in height, 1 - 1.5 cm in width, and 1 centimeter in depth. The isthmus is identified, anterior to the trachea as a uniform structure that is approximately 0.5 cm in height and 2 - 3 mm in depth. The pyramidal lobe is not seen unless it is significantly enlarged. In the female, the upper pole of each thyroid lobe may be seen at the level of the thyroid cartilage, lower in the male. The surrounding muscles are of lower echogenicity than the thyroid and tissue planes between muscles are usually identifiable. The air-filled trachea does not transmit the ultrasound and only the anterior portion of the cartilaginous ring is represented by dense, bright echoes. The carotid artery and other blood vessels are echo-free unless they are calcified. The jugular vein is usually in a collapsed condition and it distends with a Valsalva maneuver. There are frequently 1-2 mm echo-free zones on the surface and within the thyroid gland that represent blood vessels. The vascular nature of all of these echoless areas can be demonstrated by color Doppler imaging to differentiate them from cystic structures. [6,7] Lymph nodes may be observed and nerves are generally not seen. The parathyroid glands are observed only when they are enlarged and are less dense ultrasonically than thyroid tissue because of the absence of iodine. The esophagus may be demonstrated behind the medial part of the left thyroid lobe, especially if it is distended by a sip of water. (FIGURE 2)
|
| Figure 1. Sonogram of the neck in the transverse plane showing a normal right thyroid lobe and isthmus. L=small thyroid lobe in a patient who is taking suppressive amounts of L-thyroxine, I=isthmus, T=tracheal ring ( dense white arc is calcification, distal to it is artefact), C=carotid artery ( note the enhanced echoes deep to the fluid-filled blood vessel), J=jugular vein, S=Sternocleidomastoid muscle, m=strap muscle. |
 |
| Figure 2. Sonogram of the left lobe of the thyroid gland in the transverse plane showing a rounded lobe of a goiter. L=enlarged lobe, I= widened isthmus, T=trachea, C=carotid artery ( note the enhanced echoes deep to the fluid-filled blood vessel), J=jugular vein, S=Sternocleidomastoid muscle, m=strap muscles, E=esophagus. |
Thyroid sonography plays little or no useful role in the management of patients who have a normal thyroid examination and the procedure is not cost effective as a screening test. [1] Nevertheless, some thyroidologists advocate almost routine use of ultrasonography at the time of physical examination to discover subclinical, nonpalpable thyroid abnormalities, which will be discussed presently, and to enhance the sensitivity and accuracy of palpation. A more cost-effective approach is to employ thyroid sonography selectively to supplement or confirm a physical examination when clinical perception is confused by obesity, great muscularity, distortion by abnormal adjacent structures, tortuous regional blood vessels, a prominent thyroid cartilage, metastatic tumor, lymphadenopathy, or prior surgery. In practice, the procedure may be used to supplement an examination when there is uncertainty about the palpation. In the academic situation, sonography is useful to teach palpation of the thyroid gland.
There are claims that
ultrasonography can offer insights into thyroid function. For
instance, among 4649 randomly selected adult subjects one
investigation found that there was a correlation between thyroid
hypoechogenicity and higher than average levels of serum TSH, even in
subjects without overt thyroid disease. [7A]
Thyroid sonography probably is not cost effective in evaluating the average patient with thyroid enlargement. Since thyroid goiters are common and rarely associated with malignancy, there is little useful purpose to sonographic documentation of the size, shape, or uniformity of a goiter. However, sonography may be used in a goiter to identify for biopsy nonpalpable thyroid nodules. The value of aspirating a selected nodule in a goiter is under current scrutiny. At this time, the data seems persuasive that the incidence of cancer in a particular nodule in a goiter is independent of the number of sonographically identified nodules, in distinction to prior belief. Therefore, this practice seems worthwhile. [8,9]
At times, it will be useful to know the ultrasonic appearance of a dominant nodule in a goiter, a tender spot, a region of focal hardness because it might give a clue about pathology. [1] (FIGURE 2) For example, sonography can identify one region in a goiter whose echo pattern is distinct from the rest of the goiter suggesting a second type of pathology, especially if the region is surrounded by an incomplete and irregular sonoleucent rim, has punctate microcalcifications or Doppler examination reveals internal vascularity. The significance of these ultrasonic features will be discussed below. Among the lesions that have been demonstrated in goiters using sonography are neoplasms and lymphoma. Other uses of sonography in goitrous patients include: differentiation of thyroid enlargement from adipose tissue or muscle, identifying a large unilateral mass in distinction to an asymmetric goiter, confirming substernal extension, providing the correct interpretation to varying clinical impressions among several examiners, and objectively documenting volume changes in response to suppressive therapy with thyroid hormone, which may be particularly useful information when patients change physicians.
An interesting public
health use of sonography in underdeveloped countries has been to
objectively identify goiter as a screen for iodine deprivation.
Furthermore, in the epidemiological setting, with proper ultrasound
equipment, assessment of thyroid volume and prevalence of thyroid
nodules, but not echogenicity or echographic pattern, are comparable
among different observers. [10]
Sonography probably is not cost effective in patients with thyroiditis or Graves' disease. It is of academic interest, but little limited practical clinical consequence to identify sonographically relatively unique patterns in certain patients with these disorders. However, several publications have shown that the ultrasound pattern correlates with the presence of autoimmune thyroid disease and can predict thyroid dysfunction as will be discussed below. In subacute thyroiditis, the severely inflamed thyroid reflects very low intensity echoes, which is generally not seen with any other thyroid disorder. [11] In the inflamed portions of the thyroid gland there is no increased vascular flow pattern on Doppler examination. The non-involved regions demonstrate normal vascularity and hemodynamics. In the recovery phase of subacute thyroiditis, the thyroid regains isoechogenicity and a Doppler study may show slightly increased vascularity. [11,12, 12A, 12B, 12C] Hashimoto's thyroiditis and Graves' disease show moderately heterogeneous, reduced echogenicity. [13,14,15,16,17, 17A] The diagnostic precision of this pattern on thyroid sonography was compared to that of anti-thyroid peroxidase antibody (TPOAb) concentration in 451 ambulatory patients with unknown thyroid status, excluding those with suspected hyperthyroidism or on drugs known to cause hypothyroidism. There was high intraobserver and interobserver agreement on the abnormal thyroid ultrasound patterns, which were judged highly indicative of autoimmune thyroiditis and allowed the detection of thyroid dysfunction with 96% probability. [18] It has been reported that among 55 patients with hyperthyroidism (29 Graves' disease and 26 toxic nodules), color flow Doppler examination was useful to differentiate the etiology. Increased blood flow was successful in differentiating untreated Graves' disease from the Hashimoto’s thyroiditis, which had similar gray scale findings, (p < 0.001) and controls (p < 0.001). Hot nodules could also be differentiated from cold nodules because of more prominent vascular patterns and significantly higher peak systolic velocity values (p < 0.001). [18A] In another investigation, patients with postpartum thyroiditis who had both high levels of antithyroid peroxidase antibody and a hypoechogenic thyroid gland also had a high risk of long-term thyroid dysfunction. [19] In 119 patients with postpartum thyroiditis and 97 normal post-partum women as the control group, thyroid hypoechogenecity was present in 98.5% of patients and 7% of the control group (p < 0.001). Initially, mean thyroid volume in the patients with thyroiditis was 77% greater than in the control group. After remission, mean thyroid volume decreased by 25% in the thyroiditis patients. Twelve months after delivery, hypoechogenicity persisted in 4 patients.[19A]
Especially in Graves' disease, color Doppler imaging of the thyroid can demonstrate diffuse hyperemia of the thyroid gland [20] that has been called a "thyroid inferno". [21] In patients with amiodarone-induced thyrotoxicosis, Doppler flow sonography has been reported to differentiate two types of disorder with implications for therapy.[22, 22A, 23, 23A] Patients with moderate to high vascular flow had underlying thyroid disease, such as latent Graves' disease or nodular goiter. The latter are at risk of iodine-induced thyrotoxicosis (Type I). Those who had no demonstrable vascular flow had no apparent prior thyroid disease (Type II). The clinical value of this observation is that the Type II patients seem to respond to treatment with glucocorticoids. In contrast, the Type I patients were felt to respond to a combined regimen of methimazole and potassium perchlorate. [22] Although this conclusion was based on a small number of patients, the observations were confirmed in a retrospective case-note audit of 37 patients. [23] Interestingly, in that study, euthyroid amiodarone-treated patients failed to show hyperactive flow. [22] Looking at the data from the perspective of patients who had been treated for amiodarone-induced thyrotoxicosis, in a retrospective study of 24 patients, responsiveness to prednisolone correlated poorly with the absence of enhanced blood flow in the thyroid glands, but the presence of enhanced flow appeared to correlate with non-response to prednisolone. [22A] Interleukin 6 (IL-6) levels correlated with the ultrasound classification in one study [22], but not in another [23]
An important application of standard sonography in patients with thyroiditis or Graves' disease is to assess for coincidental tumor or lymphoma those thyroid glands that have focal firm consistency, or are enlarged or painful. [1] For instance, the focal lesion could be cancerous. In one report, patients with Hashimoto's thyroiditis had sonography to detect nodules and then ultrasound-guided aspiration biopsy to elucidate the nature of the lesion. Two of 24 patients (8.3%), from aspirates of 31 nodular lesions, had papillary thyroid cancer. [23B]
In patients with thyrotoxicosis, sonography can assess the size of the thyroid gland to facilitate I-131 dosimetry. The size of each lobe is measured in the sagittal and transverse planes to provide the length (L), anterior-posterior depth (D), and transverse width (W), respectively. The volume of each lobe is calculated using the formula for a prolate ellipse: (Vol.= 0.5 [L x D x W] ). 3D echography may improve he accuracy of assessment of thyroid volume. [23C]
Doppler sonography may become a useful tool for the clinical endocrinologist in the management of patients with Graves’ disease if recent observations are confirmed in large populations. Color-flow mapping of the thyroid gland may have a role in the selection of an optimal dose of Methimazole needed to maintain a euthyroid state in patients with Graves' disease. [24] It remains to be determined if it will be cost-effective to initiate therapy with an optimal dose selected in this fashion, as opposed to using a full blocking dose and either adjusting downward as dictated by the T-4/T-3 response or adding L-thyroxine to maintain a euthyroid status. Another study has characterized Doppler ultrasound data from patients with Graves' disease, Hashimoto's disease, and goiter to obtain a "hemodynamic index" to ascertain when antithyroid drugs should be withdrawn or ablative therapy given in patients with Graves' disease. The hemodynamics in the thyroid were significantly different between untreated thyrotoxic and medically well-controlled patients but there were no significant differences between untreated or medically poorly controlled patients. It would be interesting to ascertain whether the hemodynamics permit an identification of a subset of well-controlled patients who will relapse after a course of therapy. [25] Furthermore, Doppler sonography has provided data from 40 patients with Graves' disease showing significantly increased thyroid blood flow in euthyroid patients who presented early in relapse after withdrawal of antithyroid drug therapy when compared with 16 age-matched normal control subjects. Conversely there were no significant differences in euthyroid patients who remained in remission when compared with normal controls. [26] The value of quantifying thyroid blood flow at the time of diagnosis has been assessed in 24 patients with Graves' disease, using percutaneous spectral Doppler recordings from the thyroid arteries, in an attempt to predict the likelihood of remission following withdrawal of antithyroid drug therapy. The mean duration of treatment was 14 months and follow-up in 13 women was at least 18 months (range: 18 - 39 months) after antithyroid drug withdrawal. Mean peak systolic velocity and volume flow rate values as well as thyroid volume measured at the time of diagnosis were significantly higher (139 cm/s, SD 46; 195 ml/min, SD 170; 52 ml, SD 18) in patients who relapsed after drug treatment compared with patients in remission (71 cm/s, SD 27; 67 ml/min, SD 61; 25 ml, SD 13). [26A] Thyroid hypoechogenicity at onset of Graves’ disease is probably not a reliable prognostic index of relapse after medical treatment. However, the absence of thyroid hypoechogenicity after methimazole treatment seems to be a favorable prognosticator of remission. [26B] In another investigation, Doppler ultrasound determined increased peak systolic velocity in the inferior thyroid artery in untreated hyperthyroid patients with Graves' disease was significantly and positively associated with the maintenance dose of methimazole needed to keep TSH normal. [26C]
Normoechoic Graves' hyperthyroid glands seem to be more resistant to therapy with I-131than hypoechoic thyroids. [26D]
Another example of the value of Doppler ultrasound relates to Lugol's solution that has been used traditionally prior to thyroid surgery for Graves' disease because it was thought to reduce the vascularity of the thyroid gland. Doppler echography has demonstrated a significant decrease in thyroid vascularity in patients with Graves' disease after seven days of Lugol's solution, confirming the rational rationale of this form of treatment. [27] Preoperative treatment with Lugol’s solution decreased the rate of thyroid blood flow and vascularity, as assessed by Doppler evaluation and also decreased intraoperative blood loss during thyroidectomy in another investigation. [27A]
Doppler examination has
been used trans-vaginally in pregnant women with Graves’
Disease to depict and assess the size of the fetal thyroid gland.
Clinical benefits might include facilitating adjustment of the
mother’s dose of antithyroid drug and anticipating or
preventing fetal and neonatal hypothyroidism. The authors suggest
that when reduction of the medication does not result in decrease in
the size of the fetal goiter, trans-placental passage of thyroid
stimulating immunoglobulin should be suspected. [27B]
The
sonographic patterns of thyroid lymphoma have been be classified into
three types based on internal echoes within the suspected lesion, the
border of the lesion, and the intensity of the echoes behind (deep
to) the lesion. The echoes behind the lesion in each type of lymphoma
are increased, presumably because of enhanced transmission of the
ultrasound through the lesion. In the nodular type of lymphoma, the
internal echoes within a nodule are uniform and hypoechoic (may be
sufficiently hypoechoic to be pseudocystic). The border between
lymphoma and non-lymphomatous tissue is well-defined and the
borderline is described as “broccoli-like or coastline-like”
irregularity. The diffuse type of lymphoma looks like goiter.
Internal echoes are also exceedingly hypoechoic but the border
between lymphoma and non-lymphomatous tissues is not distinct. It is
difficult to differentiate the diffuse type lymphoma from chronic
thyroiditis. The mixed type lymphoma shows multiple, patchy
hypoechoic lesions, each with enhanced posterior echoes. [27C]
Thyroid nodules can be identified by sonography because they distort the uniform shape or echo pattern of the thyroid gland. Thyroid nodules may be large or small. They may distort the surrounding thyroid architecture or may dwell within a lobe and be unobtrusive. They may be solid tissue or consist of solid areas interspersed with echo-free zones that represent fluid-filled hemorrhagic or straw-colored degenerative zones. (FIGURE 3) A smooth, globular area without echoes generally represents an epithelial-lined cyst, which is a rare benign lesion. [28] (FIGURE 4) Most thyroid nodules have a less dense ultrasound appearance than normal thyroid tissue and a few are more echo-dense. [4] A sonolucent rim, which is called a halo may be present around a nodule. This represents a capsule or another interface, such as inflammation or edema, segregating the nodule and the rest of the gland. Doppler technique may demonstrate increased vascularity within a nodule or a halo. [7] (FIGURE 5)
Nodules are not a single disease but are a manifestation of different diseases including adenomas, carcinomas, inflammations, cysts, fibrotic areas, vascular regions, and accumulations of colloid.
 |
| Figure 3. Sonograms showing longitudinal (left panel) and transverse (right panel) images of the left lobe containing a degenerated thyroid nodule. Note the thick wall and irregularity. N=nodule, H=hemorrhagic degenerated region. |
 |
| Figure 4. The left panel shows an anterior scintiscan of a euthyroid patient who had a tense nodule in the left thyroid lobe. The nodule is "cold". * * * =nodule. The right panel shows a sonogram of the neck in the longitudinal plane revealing that the nodule is a smooth-walled cystic structure without internal echoes. between the + + symbols. Note the dark dense echoes distal to the cyst. C=cyst, L=thyroid lobe. |
 |
| Figure 5. Sonogram of the neck in the longitudinal plane showing a hypoechogenic nodule that was surrounded by an echo free rim, called a halo. Doppler examination demonstrated great vascularity in the halo, identified as bright spots. Small blood vessels are also seen elsewhere. N=nodule, L=heterogenous thyroid lobe, m=muscle. |
The ultrasonic appearance of a thyroid nodule does not reliably differentiate a benign thyroid lesion and cancer. [1,4] Furthermore, sonography cannot identify a specific kind of tumor such as a Hurthle cell lesion. [28A] However, there are distinctions in echo-density, calcifications, a rim, and vascularity that favor a benign or malignant diagnosis among thyroid nodules. [28B 28C] These characteristics are summarized in TABLES 1&2. But, the features described reflect statistical probabilities and not dependable criteria.
Thyroid malignancies tend to be hypoechoic when compared with the rest of the thyroid. [28,29,30,31,32] Since most benign thyroid nodules, which are far more common than malignancies, are also hypoechoic, this finding is not particularly useful except that it is reasonably safe to conclude that hyperdense nodules are probably not cancerous. One group of investigators has concluded that hyperechogenic lesions occurring in thyroiditis-affected thyroid glands bear no-clinical relevance. Therefore, they advocate that aspiration biopsy of these nodules is not advisable. [32A]
The presence of calcification is also not a straight-forward diagnostic aid. Micro calcifications are relatively more common in malignant lesions than benign and may represent psammoma bodies. Micro calcifications have been reported as demonstrating a 95.2% specificity for thyroid cancer, but a low sensitivity of 59.3 % and a diagnostic accuracy of 83.8%. [31] However, large coarse calcifications and calcifications along the rim of nodule are common in all types of nodules and reflect previous hemorrhage and degenerative changes. Thus, thyroid calcifications as detected by sonography provide little practical help in identifying cancer in the individual case. In one study, the highest incidence of calcification was found in thyroid cancer (54%), followed by multinodular goiter (40%), solitary nodular goiter (14%), and follicular adenomas (12%). The authors reported that calcifications in a "solitary" nodule in a person younger than 40 years person should raise a strong suspicion of malignancy because of a relative cancer risk of 3.8 versus 2.5 in patients older than 40 years with calcified nodules. [33] It is useful to note that large calcifications are seen with increased frequency in medullary thyroid carcinoma. [34]
A halo around the nodule may be seen with benign or malignant conditions. It suggests that there is an acoustic interface that does not reflect the ultrasound across two different types of histology in the region, the nodule and the surrounding thyroid. [28,35,36]. Some observers have suggested that cancer should be suspected when the periphery of a halo has a blurred appearance. We have not found that characteristic reliable.
There have been investigations of a possible correlation between the degree of definition of the edge of a nodule and the likelihood of malignancy and even of the predictability of aggressive characteristics of a papillary cancer. In one series of 155 cases, poor definition of a nodule’s edge was observed in 21.5% of patients, all of whom showed worse disease-free survival (p = 0.0477) than those with a well-defined edge. Furthermore, this finding was directly linked to US-diagnosed lateral node metastasis (p = 0.0001).[36A]
An analysis of the hemodynamic characteristics of a nodule by high resolution pulsed and power Doppler ultrasonography also may offer valuable preoperative diagnostic insights. For example, one study compared the vascular pattern and the velocimetric parameters, such as peak systolic velocity, end-diastolic velocity, pulsatility index or resistance index between 25 follicular adenomas and 10 follicular carcinomas. Eight of 10 patients with follicular carcinomas showed moderate increase of intra-nodular vascularity using “Power Doppler”. In contrast, the 21 out of 25 follicular adenomas showed only a peripheral rim of color flow. Furthermore, the velocimetric analyses were significantly higher in the patients with cancer than those with adenomas. [36B] Bayes' mathematical theorem has been used to evaluate the prognostic value of enhanced intranodular blood flow by Doppler analysis in determining the probability of cancer in thyroid nodules that demonstrate a follicular aspiration cytology. The sensitivity of enhanced intranodular flow by Doppler analysis for detection of thyroid carcinoma was 80%-86% and the specificity of indicating cancer ranged from 85% to 89%. The probability that a nodule is thyroid cancer before a Doppler test was estimated at 12%-14%. After the examination the probability of thyroid cancer declined to 3% when there was no central intranodular flow and increased to nearly 50% in the presence of intranodular flow. [36C] In one investigation of 230 patients, 203 of whom were treated surgically, the addition of color flow Doppler imaging to conventional sonography increased the screening sensitivity and accuracy in identifying 36 malignant thyroid nodules from 71.9% to 83.3%. [36D] Ultrasound contrast medium Doppler sonography may also enhance the diagnosis of thyroid cancer. In one investigation, carcinomas showed a significantly earlier arrival time of Levovist in the nodule than nodular hyperplastic benign nodules or adenomas. [36E]
There have been observations that some cancers tend to have a non-globular, “tall” shape, as if growing in one plane, but we have not observed that characteristic as diagnostically useful but “tall” nodules should be viewed with enhanced suspicion.
Ultrasonographers have observed that colloid nodules, which are benign with high probability, have a characteristic appearance of a “Stack of pancakes” or “Puff pastry like a Napoleon” and may appear as a small, echogenic, bright spot with “comet-tail shadowing”. There seems to be merit to these characteristics, which will require critical scrutiny. Furthermore, it is important to be aware that a cancer may co-occur in an otherwise nodular or colloid goiter.
| Table 1. Ultrasound characteristics associated with an increased thyroid cancer risk |
|
1. Hypoechoic 2. Microcalcifications 3. Central vascularity 4. Irregular margins 5. Incomplete halo 6. Tall>wide 7. Documented enlargement of a nodule
|
| Table 2. Ultrasound characteristics associated with a low thyroid cancer risk |
|
1. Hyperechoic 2. Large, coarse calcifications (except medullary) 3. Periperal vascularity 4. Looks like puff pastry or Naponeon 5. Comet-tail shadowing |
Until recently, the diagnostic evaluation of patients with a single palpable thyroid nodule was not thought to benefit from ultrasonography. However, investigation has demonstrated that routine sonography frequently identifies additional nodules that are non-palpable, and probably should be biopsied if they are over 1 cm. in diameter, as discussed below. Furthermore, the results of sonography may influence a management decision when the results of needle biopsy are only “suspicious”. Among 303 patients who had thyroid nodules with an aspiration biopsy reading of suspicious for papillary thyroid cancer and a surgical pathologic diagnosis, a pre-biopsy ultrasound examination had a positive predictive value of 94.9%, and negative predictive value of 80.9%. 36F
Sonography has a very limited role in preoperative staging of a nodule that is suspected of thyroid carcinoma. In one study, the sensitivity of depicting metastases to lymph nodes was 36.7% and of tumor invasion of the muscles 77.8%, trachea 42.9%, and esophagus 28.6%.[37]
Postoperatively,
sonographic features of nodules in a thyroid bed cannot distinguish
recurrent thyroid cancer and benign thyroid remnants. [37A]
It is generally agreed that for a palpable thyroid nodule fine-needle aspiration biopsy is the best test to assess malignancy. Furthermore, a diagnostic strategy using initial FNA for palpable thyroid nodules was found to be more cost-effective than starting with ultrasonography or scintigraphy. [37B]
There is consensus, however, that palpation does not accurately predict the need for sonography. Evidence is mounting in support of routine sonography for patients with palpable uninodular thyroid disease and goiter because non-palpable nodules are common. One suspects that routine sonography will be employed especially when palpation is uncertain or skills tentative. Thyroid ultrasonography has been reported to provide information to the clinician that importantly alters management in 63% (109/173) of patients who were referred to a tertiary endocrine group. Sonography showed an indication for needle aspiration or demonstrated that the procedure is not necessary. Among 114 patients who were referred because of a solitary thyroid nodule, ultrasonography detected additional nonpalpable thyroid nodules that were at least 1 cm. in diameter in 27 patients and no nodules in 23. Thus, among 50 patients sonography lead to an almost equal number of additional aspirations or no biopsy. Among 59 patients who were referred because of goiter, sonography showed no nodule in 20, thus avoiding biopsy, and revealed nodules at least 1 cm. in diameter in 39 patients, requiring aspiration that was not anticipated. [9]
However, with respect to
routine sonography, it is important to comprehend that the optimal
clinical value of the test depends on the quality of the ultrasound
examination, including the maturity of the examiner and the
characteristics of the equipment. Grossly misleading results are
common with quick, incomplete studies and unsophisticated machines or
substandard readouts. Therefore routine sonography in a medical
office or clinic or by a non-trained general radiologist will require
proper preparation. Without study and training, there are likely to
be unacceptable results, adverse outcomes, and negative publicity.
Furthermore, the cost-effectiveness of ultrasonography in discovering
malignancy or of properly selecting patients for surgery as opposed
to the hazard and needless expense that derive from increased
needless surgery that might be attributable to sonography has yet to
be critically examined.
Sonography demonstrates micronodules (incidentalomas) of the thyroid that are less than one centimeter in diameter, non-palpable, common, and of questionable clinical significance.[38](FIGURE 6) Whereas palpable thyroid nodules occur in 1.5 - 6.4 % of the general population, [39] the incidence of non-palpable nodules is at least ten fold greater when the population is screened by ultrasonography. [40] Non-palpable nodules increase with age to involve approximately 50% of older adults especially women. The risk of malignancy among palpable nodules is approximately 10% and in micro nodules had been generally thought to be considerably smaller. [41] However, investigations reported a similar incidence of cancer in palpable and non-palpable thyroid nodules.[42,42A,42B] One study actually reported a higher incidence of malignancy among incidentally discovered nodules than among clinically detected ones. [43] Furthermore micro-cancers seem to behave clinically in a fashion that is similar to larger cancers. Among 317 incidentalomas that were aspirated from 267 patients the rate of malignancy was 12% in a retrospective analysis. In addition, in this subgroup, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumors at surgery, suggesting that the small size alone does not guarantee low risk in incidentally found thyroid cancers.[43A] Therefore, their clinical impact is quite small but they cannot be ignored.
 |
| Figure 6. Sonograms of the right thyroid lobe in the longitudinal plane showing a 2.7 x 3.2 mm hypoechoic nodule that is delineated in the lower panel by the xx and ++ symbols. Note the linear hypoechoic structure below that (arrow). In the upper panel the bright structure is a Doppler signal and indicates a blood vessel below the nodule. The nodule is not vascular. |
Non-palpable nodules or those that have escaped detection on examination are often discovered incidental to imaging of the neck for vascular or neurological reasons. These thyroid lesions should be managed like other “Incidentalomas”, with observation, dedicated thyroid sonography, aspiration biopsy, or even surgery, as indicated by the data and mature judgment. This opinion is supported by an investigation in which thyroid nodules were found in 9.4% (168) of 2004 consecutive patients undergoing carotid duplex ultrasonography. There was high correlation of the nodules with standard thyroid ultrasonography (presence of nodules, 97% (64 of 66) and size, r = 0.95, P<.001). Twenty-one (32%) of the nodules were smaller than 1cm. Only two patients with unilateral masses noted on carotid duplex had a normal thyroid sonogram. Twenty-nine of the 66 (44%) were selected for fine-needle aspiration biopsy due to cancer-risk criteria. These results lead to surgery in 13 of the 66 (19.7%); pathology included 5 patients with cancer (3 with papillary cancer, 2 with follicular cancer), 4 patients with a follicular adenoma, and 2 with lymphocytic thyroiditis. [43B]
How successful is ultrasound-guided cytological diagnosis of non-palpable nodules? Intuitively, it is generally believed that success varies inversely with nodule size but the data are not conclusive The diagnostic yield with nodules as small as 10 mm has been reported as comparable to that of aspirating of larger nodules [42]. Adequate material for cytological analysis reportedly was obtained in 64% of 0.7-cm lesions and 86.7% of 1.1 cm nodules. For 1 cm. or smaller nodules, the sensitivity was 35.8% and false-negative results were seen in 49.3%. [43C] In contrast, a study of aspirates from 317 nodules in 267 patients reported that the size of impalpable nodules (0.9 +/- 0.3 cm, a range of 0.2 cm to 1.5 cm) was not related to the probability of getting an adequate specimen for cytological diagnosis. [43D] We generally do not attempt to aspirate nodules smaller than 8mm but have had limited diagnostic success in sampling incidentalomas as small as 5 mm and approximately 70 percent success with nodules at least 8 to 10 mm. However, considering the minimal clinical importance of thyroid microcarcinoma, the clinical value of aspirating nodules this small is uncertain. Furthermore, based on a review of the literature, Mazzaferri et.al. have concluded that thyroid nodules 5mm or smaller have a high rate of false positive ultrasound findings and often yield inadequate cytology on fine needle aspiration biopsy. Therefore, they advise that nodules of this size with no other suspicious clinical findings should not undergo routine needle biopsy, even if they appear ultrasonographically suspicious. [43E]
Sonography has changed our clinical perception of what is a normal thyroid gland and has advanced medical practice. Current high resolution ultrasonography of the thyroid has permitted the clinical detection of nodules that are as small as 2 mm. It frequently demonstrates that what appears to be a normal gland, actually contains a non-palpable nodule or is a subclinical nodular goiter. [30,41] ) It may show that a solitary nodule on palpation really is a clinically palpable nodule in a gland that is subclinically multinodular. Pathologists have long known about the ubiquitous nature of thyroid micro-nodules and the relative frequency of occult thyroid carcinoma, which is rarely of clinical consequence. Now the clinician is often confronted with a conundrum in management because micro-nodules are discovered as a consequence of investigation for orthopedic, neurological, or vascular pathology or a palpable thyroid nodule. As a rule, their discovery occasions needless expense, concern, and therapy because it is not known which of the myriad nodules that have been revealed is, or will progress to become a clinical cancer.
It remains for future investigation to determine the appropriate management for micro-nodules. However, since it is rare for one of these lesions to represent an occult thyroid cancer and rarer still for one to become a clinically significant malignancy, indiscriminate surgery, which has an exceedingly small yield of cancer, seems ill-advised. Rather, periodic sonographic reassessment for possible growth of the nodule appears preferable to dismissal of the problem as unimportant. The role of ultrasound guided needle biopsy in the management of these patients, especially when there is a history of exposure to therapeutic x-ray will be discussed below.
Not all "incidentalomas"
in the region are thyroid in origin. Parathyroid adenomas have been
observed within the thyroid gland or in the usual parathyroid
anatomic location when ultrasonography was performed to evaluate
thyroid nodules. [44]. An example of a misidentified lesion that
demonstrates the extent of the lack of specificity of a “sonographic
nodule” is an esophageal tumor that was erroneously
characterized as thyroid. [44A]
Even in the thyroid cancer patient, enlarged benign thyroid lymph nodes are more common than malignant ones. Nevertheless, ultrasonography may be useful to diagnose and follow lymphadenopathy in the patient with a history of thyroid cancer or if there is a history of exposure to therapeutic radiation in youth.
Normal lymph nodes are depicted by sonography as approximately 1 X 3 mm, well-defined, elliptical, uniform structures that are slightly less echo-dense than normal thyroid tissue and that have an echo-dense central hilum. Lymphadenopathy that is reactive to infection may be larger but tend to maintain an oval shape while malignant ones more often have a "plump" rounded shape. [45] (FIGURES 7&8)
 |
| Figure 7. Sonogram in the longitudinal plane of the left side of the neck after thyroidectomy showing a small, elliptical benign appearing lymph node in the jugular region. It is delineated by the xx and ++ symbols. |
 |
| Figure 8. Sonogram in the transverse plane after thyroidectomy for cancer from a muscular man. There was no palpable mass. The image shows a rounded lymph node that was cancer. C=carotid artery, m=muscle, ++ marks the node. |
Especially in children, inflammatory lymphadenopathy is common, which may complicate a search for thyroid cancerous nodes. A source of confusion in diagnosing lymphadenopathy especially in the elderly and obese subjects is fatty change in a node that may mimic a macro-metastasis at palpation. Sonography can offer a useful insight. In one study, of 110 selected patients with a total of 247 nodes, the central “fatty”, hyperechoic hilum was quite large, extending more than one third of the transverse diameter. The ratio of the long to short axes of the node and the parenchyma to fat (P:F) were obtained. Differences between mean P:F ratio in diabetic and nondiabetic patients were significant (p=0.045). The mean P:F ratio was negatively related to body mass index (BMI) (r=0.62, p=0.015) and age (r=0.54, p=0.024). All of the nodes examined with a mean P:F ratio <or= 1.2 (58) were found in patients older than 72 years and with a BMI higher than 27.8. [45A]
Ultrasound can detect cancer that is metastatic to cervical lymph nodes with a sensitivity of 92.6%. [46] In several investigations, the two most useful diagnostic characteristics are the ratio of the longitudinal to the transverse diameter of a lymph node ( L/T ratio) and the absence of a central echogenic hilum. [45, 46A, 46B, 47] In one study, the L/T ratio was less than 1.5 in 62% of metastatic nodes and greater than two 2 in 79% of reactive nodes. [47] A wide cortex or narrow hilum was observed in 90% of malignant lesions, but only 45% of benign nodes. The absence of a hilum was observed in 44% of malignant lesions, but in only 8% of benign nodes. In this study the size and uniformity of a lymph node was not helpful in differentiating benign or malignant nodes. The location of adenopathy in proximity to the thyroid in the central compartment of the neck may also be indicative of thyroid cancer. Multivariate analysis in an investigation of this question showed that only central location (odds ratio, 4.07; 95% confidence interval (CI), 1.64 to 10.10) and size (odds ratio, 5.14; 95% CI, 1.64 to 16.06) remained as significant corollaries of cancer. [47A] It is not clear if additional information about the nature of lymphadenopathy may be offered by color and spectral Doppler investigation. Although one group of investigators found that malignant nodes (29/32) more often than benign ones (6/16) demonstrate enhanced color flow signals, [48] another group observed abundant color flow signals in all enlarged lymph nodes. [49] There may be some diagnostic value to examining the ratio of systolic and a diastolic blood flow in a lymph node, which is called the resistive index. It has been reported that cancerous lymph nodes have a high resistive index (mean 0.92) while reactive nodes have a considerably lower value (<0.6).[49] Another investigator reported that metastatic nodes from papillary carcinoma frequently demonstrate prominent hilar vascularity similar to reactive nodes. [50] Among abnormal nodes that had cystic spaces, one study showed a high likelihood of papillary thyroid cancer as assessed by FNA. Cystic changes were not seen in 43 of 63 pathologic nodes that were either metastatic from other malignancies (22 patients) or benign reactive lymphadenopathy (21 patients). [51] Since cystic spaces due to necrotic material may be seen in tuberculous nodes, caution is warranted when one interprets the clinical meaning of this finding. An important diagnostic aspect of cystic masses that are lateral to the thyroid is demonstrated by one report that showed that among 37 adults (age 16-59 years), 10.8% of cervical cysts were lymphatic metastases from occult thyroid carcinoma.[51A] Others have reported similar observations and the point has been made that in younger patients, the lymph nodes might appear purely cystic, thereby mimicking branchial cysts. [51B]
The addition of CT of the neck to ultrasonography was found to be slightly superior to sonography alone for the detection of metastatic lymph nodes in the lateral compartment of the neck but not in the central compartment in patients with papillary thyroid cancer. [51C]
Cytological and
immunocytological analysis of enlarged cervical lymph nodes, using
the ultrasound-guided aspiration biopsy technique described below,
can differentiate thyroid cancer metastases and inflammatory
lymphadenopathy. [52]
The thyroid ultrsound report must answer the question that has been posed by the clinician and not be just a routine recitation. The ultrasonographer or the thyroidologist who interprets the images should note and record in the report the features listed in Table 3 and call specific attention to the features that reveal a higher than average risk of malignancy.
| Table 3. A thyroid ultrasound report should include mentioning the following: |
|
1. Each lobe, including isthmus a. dimensions b. uniformity of shape c. echogenicity i. hyperechoic ii. hypoechoic iii. isoechoic d. vascularity i. physiologic ii. increased iii. decreased iv. avascular e. nodules i. number A. all nodules uniform characteristics B. one nodule with noteworthy characteristics * ii. margins iii. echogenicity
1. a. i. A. hyperechoic B. hypoechoic * C. isoechoic ii. composition A. solid B. cyst C. complex (solid with cystic component) iii. shape A. globular B. longer or taller than wide * iv. margin A. well-defined B. ill-defined * C. halo
1. a. i. A. I. complete
1. a. i. A. I. incomplete *
1. a. i. A. no B. halo ii. vascularity A. periperal B. central * C. avasular iii. calcifications A. punctate * B. coarse C. egg-shell iv. other features A. puff-pastry “Napolean-like” layers B. bright spot with “comet tail shadowing” 1. lymph nodes * a. location i. ipsolateral ii. contralateral iii. anatomic site b. shape i. oval ii. globular * c. hilum i. fatty ii. vascular iii. absence * d. margin i. well-defined ii. ill-defined * e. blood-flow from periphery * f. vascularity i. increased ii. physiologic g. calcifications i. punctate * ii. coarse iii. egg-shell h. composition i. solid ii. complex with cystic component * i. impact on surrounding structures i. deforms * ii. no impact 1. extra-thyroid mass a. anatomic site b. ultrasonic characteristics 1. comparison with prior examination a. prior date b. comparison based on report or images? c. technically comparable? i. yes ii. no d. characteristics of lobes e. characteristics of nodules
characteristics of nodes
|
|
|
|
|
|
|
|
*Special attention: may be associated with increased risk of cancer.
|
In the patient with a
history of therapeutic irradiation to the head and neck in youth, the
thyroid cancer risk may be as high as 30%. Since thyroid nodules may
be detected with ultrasound before they become large enough to be
palpable, sonography has been employed to screen irradiated people
for tiny nodules. This selection process is quite inefficient because
in the process, many more benign nodules are found than malignant
ones. Consequently, some clinicians prefer not to detect
micro-nodules contending that they are clinically irrelevant. In
contrast, the author prefers to obtain a potentially useful baseline
sonogram, but not to act on the presence of a micro-nodule unless a
repeat sonogram after an interval of time demonstrates its growth or
there are other circumstances that heighten the suspicion of
malignancy.
Changes in the size of a nodule may be clinically important, but difficult to perceive clinically. However, sonography can accurately and objectively assess changes in thyroid nodules and the thyroid gland over a period of time. This is especially important during the course of therapy with thyroid hormone, in patients with a history of exposure to therapeutic irradiation, and when there is a history of thyroid cancer. Interval studies on such patients may be performed without discontinuing thyroid suppressive therapy, administering recombinant human TSH, or any preparation of the patient. Consequently, it is a simple matter to compare serial records which may lead to changes in thyroid management earlier than palpation alone would warrant. Furthermore, since most patients tend to change doctors and residence over a period of years, an objective assessment of the size of the thyroid gland or nodules will greatly facilitate the continuity of care.
Caution is warranted in
interpreting the meaning of changes in the volume of thyroid nodules
after fine-needle aspiration has been performed. Bi-directional
volume changes after the biopsy have been reported. [53] Therefore,
it is appropriate to assess base-line volume sonographically well
after the procedure. Following a period of observation or thyrotropin
suppression therapy, a sonogram carried out to measure size should be
done before another puncture is performed.
Sonography has become a most useful imaging procedure in patients who have had either partial or complete thyroidectomy. [54] (FIGURE 8) After examining every 1-2 years 110 patients who had partial or total thyroidectomy for thyroid cancer, one study showed that ultrasonography is the most sensitive and important way to image post surgical recurrences of thyroid carcinomas and lymphadenopathy in it's most common location, which is the neck. The authors suggest it's routine use in these patients. [55] Furthermore, a five-year observational study of 80 patients investigated the optimal initial follow-up strategy for patients who had near total thyroidectomy for papillary thyroid microcarcinoma. Sonography identified lymph node metastases in two thyroglobulin-positive and one thyroglobulin-negative patients. Whole body scanning showed no “pathological” uptake in any patient and was essentially useless, probably because differentiation of postoperative gland-remnant and tumor was not possible. Correlating with radioiodine uptake in the region of the thyroid bed, however, rhTSH-Tg was 1 ng/ml or less in 45 and more than 1 in 35 patients (r = 0.40, P < 0.0001). In this population, Tg levels probably derived mainly from small normal tissue remnants. Therefore, mild elevations of this protein are also of limited diagnostic value. After observation for 32 +/- 13 months after surgery, all node-negative patients had undetectable Tg levels while on suppressive therapy and sonography remained negative. [55A]
It is important to appreciate that sonography may yield clinically erroneous or misleading results if it is performed during the initial several months following the surgery. During this time there may be abundant lymph nodes and heterogeneous, sono-dense regions that probably reflect postoperative changes such as edema and inflammation. It is noteworthy that sonography is done without interrupting the therapy with thyroid hormone, which is used universally in the thyroid cancer patient.
Sonography may serve to uncover unsuspected disease. After less than total thyroidectomy, sonography will detect nodules in the thyroid remnant, post-operative thyroid bed or in the contra-lateral thyroid lobe, which could be benign tissue or tumor. After total thyroidectomy but not following partial thyroidectomy, nodules and adenopathy are more likely to represent cancer when the concentration of thyroglobulin is elevated. Sonography may detect this disease even before it has grown sufficiently large to be palpable. In patients in whom thyroid carcinoma has been diagnosed as the result of metastases to bone, lung or cervical nodes, sonography can detect an occult thyroid primary tumor even when the thyroid gland is normal to palpation.
One investigation has shown that Thyrotropin-stimulated serum thyroglobulin assay combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma in children, and many investigators believe, in adults also. [55B]
One group of investigators has reported that even when thyroglobulin levels remain low or undetectable after stimulation with rhTSH, sonography may identify lymph node metastases from thyroid cancer. [56]
It may be difficult to differentiate a suture granuloma from recurrent thyroid cancer. A case report demonstrated a nodule that mimicked recurrent thyroid cancer on sonography and 2-[fluorine-18] fluoro-2-deoxy-D-glucose positron emission tomography, but the diagnosis of a suture granuloma was confirmed by a US-guided fine needle aspiration biopsy. [56A]
Intra-operative ultrasonography may enhance the ability to locate and resect recurrent thyroid cancer that does not accumulate radioactive iodine. Experience in seven patients suggests that sonography was particularly helpful after external beam radiotherapy to identify tumor nodules of 20 mm or less that were invasive or adherent to the airway. [57] One investigation reported that intra-operative ultrasound performed by the surgeon influenced the management in 57 per cent (41/72) of patients by identifying non-palpable adenopathy. [57A] However, one wonders if resection of non-palpable or even larger deposits of differentiated thyroid cancer will benefit outcome since even bilateral radical neck dissection was not associated with enhanced results when compared with thyroidectomy alone. Never the less, excision of non-palpable nodules that are in proximity to a vital structure could be palliative if the cancer is removed before it invades. I can imagine that after the surgeon has completed a thyroidectomy for cancer, intra-operative ultrasonography could become standard to look for and remove undetected nodes before “closing”.
Fine needle aspiration biopsy of thyroid nodules and adenopathy has become a major diagnostic tool that is safe and inexpensive. [48,58,59,60,61,62,62A] Major untoward effects are very uncommon and include bleeding (especially in patients who use anticoagulants or antiplatelet agents or those who have a bleeding diathesis), hoarseness, and infection. Seeding the needle track with thyroid cancer is a remote consideration. [62B,62C]
The major indications for ultrasound-guided FNA are summarized in TABLES 4 & 5. Ultrasound has made placement of the needle more accurate especially for small or complex nodules or nodes. Cytopathologic interpretation is usually clinically satisfactory and promises to improve with tissue marker analysis of specimens. [63] However, the accuracy of the puncture varies considerably depending on factors that are related not only to the operator and the cytologist, but also to the patient. The latter conditions include the size, homogeneity and vascularity of the nodule or node, its location in the neck, sampling errors, and the habitus of the patient. These issues affect biopsy technique. Thyroid nodules or lymph nodes that are palpable are usually biopsied directly. In some cases, correlation of the palpable anatomy with a sonographic film may be useful. For small, complex, or deep nodules, or when a palpation-guided biopsy has resulted in an insufficient specimen, ultrasound-guided fine needle biopsy is employed, [9, 64], but with added cost and some inconvenience. Ultrasound guidance improves accuracy in puncturing the nodule. Ultrasound-guided biopsy is always required for impalpable incidentalomas and even then, it is difficult to reliably sample lesions smaller than 10mm.
Two methods for ultrasound-guided needle biopsy have been suggested: 1) A sonographer manipulates the transducer to locate the nodule and a second physician inserts the needle under direct vision, or 2) A special clamp is used to hold the transducer and fix the direction of insertion of the needle. Both require hand-eye coordination and experience is necessary to identify the spot on the skin over the target nodule to insert the needle. In our practice a dimple is produced on the skin with a blunt 1mm wooden dowel directly over the nodule as it is identified by the transducer. We have not found it appropriate to employ a "permanent marker" for this purpose, as has been suggested. [65] Furthermore, this author finds the holder cumbersome and restrictive and prefers the free hand approach.
With the free-hand method, the needle may be inserted parallel to, or at an angle to the ultrasound beam and at a distance from the transducer, aiming at the nodule. The parallel approach may be technically challenging but is "comforting" to the operator because the image of the needle shaft may be viewed as it traverses the neck and into the nodule. Never the less, many experienced operators prefer an oblique to a perpendicular approach because of its simplicity and lack of complications. The needle shaft is not imaged with this technique but its tip is seen as a very bright spot when it crosses the plane of the scan. The tip of the needle must be within the nodule during aspiration. However, even with ultrasound guidance, it is rather difficult to be certain that the tip of the needle is actually within a small nodule at the instant of aspiration, particularly if it that is less than 7 or 8 mm in diameter. at the instant of aspiration. (FIGURE 9)
 |
| Figure 9. Sonogram from an ultrasound guided fine needle aspiration biopsy showing a hypoechoic small nodule. The bright spot (above the arrows) is the tip of the needle within the nodule at the instant of aspiration. N=nodule. |
Employing Doppler technique to identify and avoid puncturing blood vessels in the region of a nodule provides a distinct advantage of ultrasound-guided aspiration over palpation-guided biopsy. This precaution reduces the amount of blood in the aspirate and facilitates interpretation of the cytology. [66] The same purpose is served by discontinuing antiplatelet and anticoagulant medication prior to a biopsy.
Samples of thyroid nodules and adenopathy may be obtained in either of two ways. One may aspirate the material with a syringe, employing a too and fro motion to produce a large quantity that frequently contains excessive blood, and complicates cytological examination. I prefer the other technique that is done with a 25 or smaller gauge needle (without a syringe) using minimal trauma and capillary action to achieve a small, concentrated sample that remains in the needle shaft. The specimen is then expelled quickly and gently on to a microscope slide with an air-filled syringe. [66A] In my experience, the capillary action aspiration method results in a superior cytological yield. I believe that syringe aspiration should be reserved for low-yield or fibrotic lesions.
Microscopic assessment of aspirates onsite for adequate cells by a cytologist at the time of the biopsy significantly reduces the number of non-diagnostic reports especially when the operator is not optimally experienced. [66B] It is likely that on-site assessment of cytopathologic adequacy of aspirates would help reduce the costs of needle biopsy, reportedly, by as much as 35.5% by reducing unsatisfactory specimens that are sent to off-site cytologists. [66C] Furthermore, in some centers cytologists actually do the aspirations. [66D]
Ultrasound-guided FNA is an accurate method of identifying suspected recurrence of thyroid cancer. One investigation retrospectively evaluated the effectiveness of ultrasound-guided fine-needle aspiration in identifying as cancer cervical nodules that were suspicious of recurrence in 37 previously treated patients with thyroid cancer. There were 29 true-positives, 6 true-negatives, 1 false-negative, and 1 inadequate biopsy. Therefore Ultrasound-guided biopsy had a sensitivity of 96.7%, a specificity of 100% and an overall accuracy of 97.2% in detecting recurrence. [66E]
Ultrasound-guided FNA may be particularly useful in investigating nodules that have been revealed by sonography in the postoperative thyroid bed. In one series, among 21 cases there were 15 recurrent cancers, 5 benign nodules such as a parathyroid gland or regenerated normal thyroid, and one false positive. [66F}
There is limited ability to reliably aspirate and accurately diagnose a non-palpable nodule or node even with ultrasound-guidance. [67] Ultrasound-guided cytological diagnosis of non-palpable nodules depends on the size of the lesion. One study suggested that the diagnostic yield of aspirating incidentally discovered, non-palpable 10 mm or larger thyroid nodules was high. [42] Another study found that sampling of material that is adequate for cytological analysis is 64% for a 0.7-cm lesion and it increases to 86.7% when a nodule is 1.1 cm. For nodules that are 1 cm. or smaller, the sensitivity was 35.8% and false-negative results were seen in 49.3%. [67A] In contrast, similar success has been reported in aspirating nodules that were 4 to 10 mm in size compared with larger nodules. [67B] We have had mixed diagnostic success in sampling nodules as small as 5 mm. A few micro-cancers have been discovered in this way. The cost-effectiveness of aspirating nodules this small is uncertain considering the small (if any) clinical significance of thyroid micro-carcinoma. We biopsy small lymph nodes when they do not have an elliptical shape and have become “plump”. Generally the width/depth must be almost 1cm to yield adequate cells. Measuring thyroglobulin obtained from a cell-poor aspirate will be mentioned below.
It has been reported from a goiter zone in Italy that as many as 52% of histologically malignant nodules in goiters were found only with the aid of ultrasound-guided FNAB. Therefore the authors concluded that ultrasound-guided aspiration should be used in areas where multinodular goiter is endemic to assess nodules that are deemed suspicious by virtue of a hypoechoic pattern, a "blurred halo", micro-calcifications, or intranodular color Doppler signal. [68] In another report of patients with endemic goiter, 44 were selected for surgery based on suspicious ultrasonography and among 24 of them who had a “cold” nodule, aspiration biopsy revealed 2 with papillary cancer and surgery disclosed 2 more cases of papillary cancer and one case of insular cancer. [68A]
One group has investigated the predictors and optimal follow-up strategy for initial nondiagnostic ultrasound-guided FNAs of thyroid nodules. Among 1128 patients with 1458 nodules that were biopsied over a 6-yr period, 1269 aspirations (950 patients) were diagnostic, and 189 (178 patients) were nondiagnostic. The authors reported that the only significant independent predictor of nondiagnostic cytology (P < 0.001) was cystic content of each nodule and the fraction of specimens with initial non-diagnostic cytology increased with greater cystic space. A diagnostic ultrasound-guided FNA was obtained on the first repeat biopsy in 63% of nodules and was inversely related to increasing cystic content of each nodule (P = 0.03). One hundred and nineteen patients with 127 nodules returned for follow-up as advised, and malignancy was documented in 5%. [69]
For non-palpable thyroid nodules, the relative importance of sonographic features as risk factors of malignancy and the use of ultrasound-guided aspiration cytology was studied in 494 consecutive patients with nodules between 8-15 mm. It is noteworthy that 92 patients (19%) had inadequate cytology and were excluded from the study. Cancers were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. The prevalence of cancer was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). The authors recommended that ultrasound-guided FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. [43]
It would appear that that no single parameter satisfactorily identifies a subset of patients whose nodule should be subjected to biopsy. In one investigation of 6136 nodules in 4495 patients, the best compromise between missing cancers and cost-benefit was achieved with at least two “suspicious” ultrasound features. The most useful were nodule shape (taller rather than wide), microcalcifications, blurred margins, and a hypo-echoic pattern. [69A] Enhanced intranodular blood flow on Doppler examination is also a very productive criterion. [36C] In our practice, the only factor the virtually excludes biopsy is hyperechogenicity.
It is difficult to decide which nodule in a goiter to biopsy. Guidelines include selection by size, the ultrasound characteristics mentioned above, and most importantly nodules that are clinically suspicious. Perhaps one may be reassured by an examination of thyroid nodules that underwent ultra-sound-guided FNA and found that the cancer risk is similar for patients with one or two nodules (over 1 cm) and decreases with three or more thyroid nodules. [69B]
Combining the results of cytology and the tumor marker, thyroglobulin may enhance the accuracy of either single predictor of thyroid cancer. One investigation reported that among 340 consecutive patients with differentiated thyroid carcinoma, who had been treated with near-total thyroidectomy, 131-I thyroid ablation, and TSH suppressive doses of l-thyroxin, rhTSH-stimulated thyroglobulin alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value of 98.2%. After adding the results of neck ultrasound, the sensitivity increased to 96.3%, and the negative predictive value to 99.5%. [69C]
Non-cytologic examination of aspirates.
Ultrasound-guided aspiration can facilitate biochemical analysis. Needle washings of adenopathy may contain thyroglobulin, revealing papillary thyroid cancer even when there are inadequate cells. It is noteworthy that assay of thyroglobulin in tissue is reportedly not effected by serum anti-thyroglobulin antibodies [69D] Furthermore, the aspirate may contain calcitonin in medullary cancer, a tumor marker such as Galectin-3 [69E] in papillary thyroid cancer, or lead to a non-neoplastic diagnosis such as tuberculosis [70] or amyloidosis. [71] One anticipates that one day aspirates may be studied routinely for biochemical products, sub-cellular components, chromosomal information, DNA, and, bacteriologic, fungal, or viral material.
| Table 4. Needle biopsy with ultrasound guidance is generally reserved for: |
|
1. A small nodule in an obese, muscular, or large framed patient. 2. Nodules that are barely palpable or non-palpable 3. Nodule size less than one centimeter. 4. A nodule that is located in the posterior portions of the thyroid gland. 5. A dominant or suspicious nodule within a goiter. 6. All nodules that yieled non-diagnostic results on a free-hand biopsy. 7. Complex degenerated nodules if a prior biopsy without ultrasound guidance has not been diagnostic. 8. Incidentalomas that have been detected ultrasonically in patients with high risk factors for thyroid cancer such as exposure to therapeutic x-ray. 9. Small lymphadenopathy.
|
| Table 5. Features That Are Associated With Data-Supported Increased Risk Of Cancer And Warrant Percutaneous Fine-Needle Aspiration Biopsy of a “Solitary” Nodule or a “Special” Nodule In A Goiter |
|
1. Clinical Features a. history of head and neck irradiation in youth b. family history of medullary (or signs & symptoms) or less so papillary thyroid cancer c. unusual firmness without calcification d. growth of nodule especially during suppressive therapy e. lymphadenopathy 2. Ultrasonic Features (at least two “suspicious” ultrasound features) a. hypoechoic nodules with one or more of the following i. irregular margins ii. enhanced intranodular vascular spots (central vascularity) iii. microcalcifications (punctate calcifications) iv. blurred margins v. taller rather than wide nodule shape vi. enlargement of a nodule when compared to prior examination b. Lymphadenopathy (palpable or ultrasonographic) 3. In a goiter, biopsy the nodule that has “suspicious” ultrasonographic features rather than the largest nodule. 4. The size or number of nodules in a gland does not correlate with risk factors. |
With all biopsy, including when sonographic guidance is employed, it is important to perform multiple punctures to improve the diagnostic yield (However, multiple punctures are associated with bloody specimens that are difficult to interpret) and one should not be convinced that a nodule has been sampled adequately unless malignancy is detected. Even with negative cytology, growth of a nodule particularly during the course of suppressive therapy should be viewed with suspicion.
There is also interest in sonographically-guided core biopsy of thyroid nodules. One group has concluded that percutaneous acquisition of tissue for histological rather than cytological evaluation is an accurate and safe alternative to aspiration biopsy in the assessment of thyroid nodules. [71A] Other investigators have reported on the use of an ultrasound-guided special, compound needle that can accomplish both aspiration and core biopsy and suggest its use when prior aspiration has been unsuccessful. [71B]
After an aspiration and cytology have demonstrated that a nodule is benign, ultrasound-guided puncture of a nodule may have a role in therapy to deliver medication or other therapy precisely into the lesion and to spare the surrounding tissue.
Percutaneous injection of ethanol has been used to reduce the function of autonomous thyroid nodules. [72] One investigation has observed 34 patients for up to three years who had percutaneous ethanol injection of autonomous thyroid nodules with a volume larger than 40 ml. The patients required 1-11 sessions of 3-14 ml of ethanol injection, (total amount of ethanol per patient: 20-125 ml). The authors report recovery of extra-nodular uptake on isotope scan and normalization of TSH levels within 3 months from the end of the treatment in 30/34 patients and an average reduction in nodule volume of 62.9%. 4/34 patients were refractory to the treatment, 3 of whom had had nodule volumes > 60 ml. There were no recurrences during 6 to 36 months of observation. [73] Another study examined 20 patients with autonomous thyroid nodules for 763 +/- 452 days after ethanol injection. A mean of 2.85 +/- 1.1 injections per patient, and a mean volume of 4.63 ml of ethanol were required (nodule volume-dependant). After a mean time of 50 +/- 23 days TSH normalized and was maintained in 16 patients (80%), whose nodular volume reduced 60.8%. Four patients (20%) did not completely respond to the treatment. [74] Less impressive but clinically acceptable results have also been observed in a study that reported a "complete cure" in only 22 of 42 patients (52%), mainly in small nodules, and little or no hormonal response in 4 patients (9%). However, nodule volume decreased in all cases and there were no recurrences or serious adverse effects. [75] In the reported series, "mild to moderate" local pain often occurred after the injections and lasted a day or two and local hematomas were seen. Major complications like permanent dysphonia or vascular thrombosis seem to be very uncommon. However, transient paralysis of the laryngeal nerve may occur. Thus this technique may be an option for large, but not very large autonomous nodules that cannot or should not be treated surgically or with I-131. [75A]
Percutaneous injection of ethanol has also been used to treat toxic nodular goiter [75,76] and thyroid masses that are recurrent after non-toxic nodular goiters have been treated surgically [76], with results that are similar to those described above.
Recurrent cysts, and cystic spaces in a degenerated solid lesion have been obliterated in this fashion. [77, 77A] Perhaps the procedure will have use in cosmetically unacceptable or very large structures. Prospective studies will be required to ascertain if ultrasound-guided placement of medication will reduce the intensity or duration of pain after the injection and improve success over palpation-directed injection.
Sonographically guided percutaneous ethanol injection is a treatment option for patients with cervical nodal metastases from papillary thyroid cancer that are not amenable to further surgical or radioiodine therapy. In a study of 21 metastatic nodes in 14 patients, all treated lymph nodes decreased in volume, some impressively. No major complications occurred in this series. [78] Yet, in other studies severe untoward effects have been reported including necrosis of the larynx and adjacent skin due to ethyl alcohol. [78A] It seems to me that this option may be palliative when there are large nodes that threaten to impact on surrounding structures. However, since ethanol-treated nodes may increase in size due to inflammation, caution is warranted especially when there are bulky nodes in the thoracic inlet or adjacent to vital structures.
Greater use of percutaneous administration of ethanol for a variety of benign and malignant conditions seems likely. However, prudence dictates that the injection should only be used when essential and not as an optional therapy to reduce the size of routine cysts, euthyroid nodules and goiters, or even non-threatening malignant nodules.
Ultrasound-guided physical energy may also be therapeutic for nodules, goiters, and cancers. Thermal coagulation of thyroid tissue with ultrasound-guided percutaneous interstitial laser is possible as demonstrated in a patient with a non-toxic autonomous thyroid nodule. The side effects were transient thyrotoxicosis and local pain. The authors of this case report suggest that photocoagulation could become a useful alternative for patients who cannot or will not undergo surgery or treatment with 131-I. [78B] One investigation evaluated in 20 patients the efficacy of ultrasound -guided laser thermal ablation in reducing the volume of hypofunctioning benign thyroid lesions that caused local compression symptoms or patient-concern, when the patients refused or were ineligible for surgical treatment. A 75-mm, 21-gauge spinal needle was inserted into the thyroid gland under ultrasound-guidance, and a flat-tipped 300-microm quartz fiberoptic guide was placed into the tissue that was to be destroyed with a 1.064-microm continuous-wave neodymium yttrium-aluminum-garnet laser for 10 minutes. Ultrasonograms were used to assess the decrease in nodule volume at 1 month and 6 months after therapy. The mean nodule volume decreased from a baseline value of 24.1 +/- 15.0 mL to 13.3 +/- 7.7 mL at 1 month (43.8 +/- 8.1%) and to 9.6 +/- 6.6 mL at 6 months (63.8 +/- 8.9%). Untoward effects included burning cervical pain, which rapidly decreased after the laser energy was turned off and treatment with betamethasone for 48 hours in 3 patients. No patient had local bruising, cutaneous burning, or dysphonia. [78C]
A potential source of therapy is percutaneous, ultrasound-guided radiofrequency heat ablation, which has been used to treat hyperthyroidism in cats. [78B 78D] Other investigators are exploring if high-intensity focused ultrasound could be a safe minimally invasive alternative to surgery to obtain localized ablation of thyroid tissue without affecting neighboring structures. [78E] Among the disorders treated have been recurrent thyroid cancers, toxic autonomous nodule,and other benign nodules. [78F,78G, 78H]
Trans-vaginal and trans-abdominal pelvic sonography has been employed to identify a 16-cm mass in the right adnexa that was a cystic teratoma, a Struma Ovarii, containing a 5-mm focus of papillary cancer within the thyroid tissue [78 I].
Ultasonography in pregnancy may become an interesting tool to assess thyroid status in utero. Gestational age-dependent and age-independent nomograms for fetal thyroid size have been developed by performing ultrasonograms in 200 fetuses between 16 and 37 weeks of gestation. [79] Fetal goiters and hypothyroidism have been studied, and successful treatment has been reported. It is thought that intrauterine recognition and treatment of congenital goitrous hypothyroidism may reduce obstetric complications and improve the prognosis for normal growth and mental development of affected fetuses. One report cited a fetal goiter diagnosed at 29 weeks of gestation during routine ultrasound examination. Fetal blood sampling performed at this time documented fetal hypothyroidism and treatment was given using a series of intra-amniotic injections of tri-iodothyronine and subsequently, thyroxine. Following birth, neonatal serum thyroid-stimulating hormone levels were within the normal range. [80] A case of fetal goitrous hypothyroidism associated with high-output cardiac failure was diagnosed at 32 weeks of gestation based on ultrasound examination. The fetus' thyroid function was examined by amniocentesis and cordocentesis. The fetus was treated by injection of levothyroxine sodium into the amniotic fluid at 33 weeks of gestation. Thereafter, the goiter decreased in size, and the high-output cardiac failure improved. [81] Assessing the fetal thyroid size ultrasonically may also be beneficial in adjusting the dose of antithyroid drug in mothers with Graves’ Disease and in preventing fetal and neonatal goiter and hypothyroidism, as discussed before. [27A] In addition, determining fetal thyroid size with ultrasonography in mothers with a history of Graves' disease has been reported to facilitate achieving normal fetal thyroid function. [81A]
There are several uses of ultrasonography in newborn infants. Normative data for thyroid length (1.94 cm. (0.24) 0.9-2.5), breadth (0.88 cm. (0.16) 0.5-1.4), depth (0.96 cm. (0.17) 0.6-2.0), and volume (0.81 (0.24) 0.3-1.7) was investigated in 100 (49 male) healthy term Scottish neonates. There was considerable variation (-0.8 to + 0.7 ml) between the two lobes in individual babies.[82] Another investigation revealed that the ratio of thyroid width to tracheal width is a simple, practical parameter for estimating the size of the thyroid gland in neonates and small children.[82A]
In permanent primary congenital hypothyroidism, ultrasonography has been reported to have identified 66 instances where the thyroid gland was not located in the usual anatomical position and hemiagenesis in one case. The diagnosis was confirmed by scintigraphy. The authors conclude that sonography might be used as the first imaging tool in patients with congenital hypothyroidism, but scintigraphy should be used to distinguish agenesis from ectopia. [82B]
Ultrasonography has been used effectively even in the field in undeveloped areas to evaluate thyroid anatomy and size in iodine-deficient regions or to search for cancer in radiation-exposed populations. Inter-observer agreement on estimates of thyroid volume has been good in epidemiologic studies but agreement on echogenicity has been poor.[83] One group correlated age, body size and thyroid volume in an endemic goiter area.[84] Another such study concluded that systematic ultrasound screening was useful in Belarus for the early detection of thyroid carcinoma in children 4-14 years of age who were exposed to radioactive fallout due to the Chernobyl accident.[85]
In contrast ultrasonography has been used to reveal that the prevalence of thyroid cancer has not increased in a population exposed to the accidental release of I-131 in Hanford, Washington during 1944-1957. [85A]
Ultrasonography has also been used to monitor thyroid nodule development among workers in nuclear power plants. [85B]
The value of ultrasonographic mass screening to uncover thyroid carcinoma depends on the cancer-risk status of the population. In a population with average cancer risk the value of screening is controversial because of the presumed low benefit/cost of the screening as contrasted with subsequent discovery of the small number of tumors that will progress to palpable, clinical, but low-virulence tumor. One group studied 1401 women who were scheduled to undergo a breast examination. Thyroid nodules were detected in 25.2% and thyroid cancer in 2.6% of all subjects. The size of the tumors was significantly smaller in the ultrasound-studied group than that of a clinically detected cancer group (P < 0.05).[86] Another group studied thyroid sonography in 5549 patients who were undergoing breast sonography. Forty-two (0.76%) thyroid cancers were found; all were papillary carcinomas. The incidence of thyroid cancer was significantly higher in the group with breast cancer than in the group who did not have breast cancer. [86A] In contrast, epidemiologic investigation of the long-term risk of developing thyroid cancer has been useful in a population with a higher risk of cancer such as irradiated people. In a prospective ultrasound examination of 2637 atomic-bomb survivors the Hazard Ratio for cancer development was significantly high at 23.6 (95% confidence interval, 7.6-72.8) and even higher, 40.2 (95%, confidence interval, 9.4-173.0) in 31 people who initially had cytologically benign solid nodules. The Hazard Ratio was only 2.7 (95% confidence interval, 0.3-22.2) in 121 subjects who had thyroid “cysts”. Importantly, sex, age, TSH level, thyroglobulin level, radiation dose, nodule volume, and increase in nodule volume did not predict cancer development in the solid nodule group but sonography did reveal the risk of cancer. [87]
There have been other novel and inventive applications of ultrasound to thyroidology and the list grows.
Just as medical practices have evolved as a result of sonography, surgical techniques may change as well. Intra-operative diagnostic sonography is already used in the patient with thyroid cancer and one suspects that it will impact favorably on surgical methods, complications and outcome. Another example of the potential is a recent report that used ultrasonography to demonstrate that routine insertion of drains into the thyroid bed to prevent formation of hematoma or seroma following thyroid surgery may not be necessary. The authors contend that not draining the wound did not adversely influence the volume of the sequestered fluid (p = 0.313) and actually was beneficial by reducing morbidity and decreasing hospital stay (p = 0.007). [88]
Thyroid sonography may also be useful before neck surgery for non-thyroid disease. In a retrospective study of 1200 consecutive patients who were treated surgically for primary tumors and who had routine preoperative neck ultrasound by the surgeon, 47%, (477/1195) of the patients had coexisting thyroid disease. Preoperative fine-needle biopsy of sonographically detected thyroid nodules was performed in 20%, which was cost-effective in limiting concomitant thyroid surgery to fewer patients (6%; 21/350). [88A]
Ultrasonic energy can be used therapeutically to destroy tissue, as discussed previously, and also to activate mechanical equipment. An example of the latter is ultrasonically activated shears for thyroidectomy that have been reported not to increase complications, shorten operative time, improve cosmetic results, and reduce the patient’s pain, without greater expense than conventional methods. [89]
Ultrasound-guided percutaneous interventional procedures to deliver medications, enzymes, recombinant materials such as RNA’s monoclonal antibodies, or energetic forces to the thyroid gland, nodules, or nodes also challenge the imagination.
Ultrasonography can estimate the rigidity of tissue, which is called Elastography. The deformability of a tissue may be assessed from a change in Doppler signal in response to externally applied pressure or vibrations, or by tracking shear wave propagation. . This phenomenon may correlate with palpable consistency and cytology of a nodule or goiter and may enhance the cancer-predictive value of sonography of non-cystic non-calcified thyroid nodules. [90,91]