Werner & Ingbar's The Thyroid: A Fundamental & Clinical Text, 9th Edition

16.Nonisotopic Techniques of Thyroid Imaging

Laszlo Hegedüs

Finn Noe Bennedbaek

Imaging has revolutionized the evaluation of patients with thyroid disease during the past three decades. However, it is important to bear in mind that the use of thyroid imaging, fascinating as it may be, is in general not evidence-based, and there have been few cost-benefit evaluations of these procedures (1).

Clinical examination and biochemical evaluation of thyroid function are fundamental in the evaluation of patients with thyroid disorders, but there is wide observer variation in the assessment of clinical findings in these patients, particularly in relation to palpation of the thyroid gland (2). Therefore, it is not surprising that imaging of the thyroid is often performed. In most cases, it cannot distinguish between benign and malignant lesions, and its clinical value is generally thought to be limited (1,3). Nevertheless, in a recent survey of members of the European Thyroid Association, 88% said they would use imaging in an index case of a euthyroid patient with a solitary thyroid nodule and no clinical suspicion of carcinoma (4). In contrast, American endocrinologists place less value on this technology, which in many patients is considered superfluous (5).

The thyroid gland can be evaluated by several imaging techniques. One is radionuclide imaging, which is discussed in detail in Chapters 12 and will not be considered further here. The others are plain radiography, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Each has advantages and limitations, and there is no absolute clinical indication for performing any of them in the majority of patients (3,6,7). The major limitation of all the techniques, in addition to expense, is their lack of specificity for tissue diagnosis. This chapter will focus on the clinical use of ultrasonography, CT, and MRI, and as far as possible compare their advantages and disadvantages (Table 16.1).

TABLE 16.1. CHRACTERISTICS OF COMMONLY USED IMAGING PROCEDURES IN RELATION TO DISORDERS OF THE THYROID


Characteristic

Ultrasound

Computed Tomography

Magnetic Resonance Imaging


Physical principle

Ultrasound

X-rays

Radiowaves/magnetic field

Availability

Good

Good

Poor

Anatomic regions best seen

Neck structures

Thorax and neck structures

Thorax and neck structures

Ionizing irradiation

No

Yes

No

Precedure may include contrast injection

Yes

Yes

Yes

Dynamic picture

Yes

No

No

Biopsy possible

Yes

Yes

No

Procedure time (minutes)

10a

20a

30a

Operator dependency

High

Medium

Midium


aVaries considerably depending on type of disease and whether biopsy is performed

PLAIN RADIOGRAPHY

A routine chest radiograph is rarely indicated for evaluation of patients with thyroid disease. An X-ray taken for another purpose can disclose mediastinal extension of a goiter or deviation or compression of the trachea caused by a goiter in the neck or mediastinum (7) (Fig. 16.1).

FIGURE 16.1. Chest radiograph showing a large mediastinal goiter causing tracheal deviation to the right and tracheal compression.

ULTRASONOGRAPHY

Ultrasonographic examination of the neck is performed using high-frequency transducers (7 to 13 MHz) with the patient in the supine position and the neck hyperextended. The transducer is coupled to the skin with gel because the sound waves do not pass through air. Ultrasonography can detect thyroid lobes or lesions as small as 2 mm. It can distinguish solid nodules from simple and complex cysts. It allows accurate estimation of thyroid size, gives a rough estimate of tissue density (echogeni city), shows vascular flow and velocity (color-flow Doppler), and aids in the accurate placing of needles for diagnostic or therapeutic purposes (8,9). Finally, it allows in utero investigation of the fetal thyroid (10). The major limitations of ultrasonography are the high degree of observer dependency (11) and the inability to identify retrotracheal, retroclavicular, or intrathoracic extensions of the thyroid (7,9,12). Images are obtained in the transverse (axial) and longitudinal (sagittal) planes, and sometimes in the oblique planes. The procedure rarely takes more than 10 minutes.

Ultrasonography is based on the emission of high- frequency sound waves and their subsequent reflection as they pass through the tissue. The amplitude of the reflections of the sound waves varies according to differences in the acoustic impedance of the various tissues. Therefore, small calcifications of 1 mm with a high acoustic impedance may be seen, whereas a large thyroid nodule with acoustic characteristics similar to that of normal thyroid tissue may not be seen. High-frequency sound waves penetrate tissue less well than do low-frequency waves, but the structural resolution of the high-frequency waves is better. The frequency used to visualize the thyroid is a compromise between the need for depth of penetration and that for resolution. The use of real time allows differentiation of static structures (thyroid, neck muscles, and lymph nodes) from moving or pulsating structures (blood vessels, esophagus).

In the past decade, transducers equipped with color-flow Doppler capabilities have made it possible to display the speed and direction of blood flow. This methodology encodes the frequency of pulsed Doppler signals by color, which are then overlaid on B-mode sonograms with their two-dimensional spatial information. Detection of velocities of less than 1 cm/s, in combination with increased spatial resolution (high-frequency ultrasonography), allows visualization of very small vessels, so that the vascularity of small areas such as thyroid nodules can be assessed (13). The introduction of power Doppler ultrasonography, displaying the strength of the Doppler signal in color, increases the gain by 10 to 15 dB, resulting in improved sensitivity for detection of flow (14). Contrast media for ultrasonography presently under development can, in principle, increase the Doppler signals by up to 25 dB (15).

Developmental Abnormalities

Ultrasonography may aid in the diagnosis of thyroid agenesis or hypoplasia (Table 16.2) (16). Thyroglossal duct cysts as well as ectopic thyroid tissue may be identified (17).

TABLE 16.2. POSSIBLE APPLICATIONS OF ULTRASOUND IN PATIENTS WITH THYROID DISORDERS


Diagnosis of thyroid aplasia or hypoplasia

Identification of ectopic thyroid tissue

In utero investigatin of the fetal thyroid galnd

Determination of thyroid size (volume)

Morphology: diffuse, uni-, or multinodular or cystic

Echoginicity: hypo-, normo-, or hyperechogenic

Blood flow determination

Aid in diagnostic biopsy

Aid in treatment: cyst aspiration, ethanol injection, or laser photocoagulation

Evaluation of reginal lymph node


The Normal Thyroid Gland

Normal thyroid lobes have a characteristic homogeneous medium-level echogenicity (Fig. 16.2), whereas that of the muscles anterior and anterolateral to the thyroid is lower (18). Posterolaterally, the thyroid is bordered by the sonolucent common carotid artery and internal jugular vein, and medially by the trachea. The esophagus with its echogenic mucosa can usually be seen behind and to the left of the trachea.

FIGURE 16.2. Transverse sonogram of the normal thyroid gland. (AT), trachea; (CA), common carotid artery; (JV), jugular vein; (MLC), longus colli muscle; (MS), sternocleidomastoid muscle; (MSH), sternohyoid and sternothyroid muscles; (T), thyroid.

A high proportion of subjects with a normal thyroid gland have small (< 1 cm in diameter) cystic or solid nodules, often called incidentalomas. Their frequency is higher in women, increases with age, and varies between countries (see Chapter 73) (19,20). The importance of these abnormalities is unclear, but because these incidental sonographic nodules are common, whereas thyroid carcinoma is not, a conservative approach is usually recommended. Biopsy or other studies are not indicated in asymptomatic subjects with an incidentally discovered nodule or cyst less than 1 cm in diameter who have no palpable thyroid abnormality (19).

Goiter (i.e., an enlarged thyroid gland) is a general diagnosis based on physical examination, but the average error of this examination is approximately 40%, and therefore it cannot be used to determine thyroid size reliably (2). Two sonographic methods for quantitating thyroid size are available. One is based on the volume of an ellipsoid, with the formula length × width × thickness × π/6 for each lobe. This method is 80% to 85% accurate, the accuracy decreasing with increasing size and degree of irregularity of the thyroid (21). The other method is based on obtaining cross-sectional images of the entire thyroid gland; its accuracy is 90% to 95%, and it is less influenced by size and degree of irregularity (22). The accuracy and precision of thyroid-volume determination using three-dimensional sonography is currently being evaluated (23). In normal subjects the thyroid volume (5 to 20 mL in adults) is positively related to body weight and age and is influenced by physiologic as well as environmental factors; for example, it is increased by low iodine intake and smoking (20,24). Ultrasonography is the most sensitive technique for screening for goiter and is widely used for this purpose in field studies (25).

Diffuse Thyroid Disease

Nonautoimmune nontoxic diffuse goiters appear on ultrasonography as diffusely enlarged thyroid lobes with a uniform or discretely irregular echo pattern. Various degrees of hypoechogenicity may be evident, but marked hypoechogenicity suggests the presence of goitrous autoimmune thyroiditis (Hashimoto's thyroiditis) (26,27). In the latter, the hypoechogenicity is not only marked but may be inhomogeneous (Fig. 16.3) (26,27). Ultrasonography cannot differentiate between goitrous autoimmune thyroiditis and lymphoma. Therefore, growth of a goiter, especially in patients with autoimmune thyroiditis receiving thyroxine (T4) therapy, should raise suspicion of lymphoma and lead to biopsy (28). The appearance of multinodular goiters also may mimic that of goitrous autoimmune thyroiditis.

FIGURE 16.3. Longitudinal sonogram showing diffuse hypoechogenicity in a patient with goitrous autoimmune thyroiditis (Hashimoto's thyroiditis)

In patients with Graves' thyrotoxicosis, the thyroid is usually enlarged and the echo pattern is homogeneous, but it may be nodular in patients with long-standing disease. Echogenicity is normal to markedly decreased. There is debate as to whether marked hypoechogenicity at the time of cessation of antithyroid drug therapy is a marker for recurrence of thyrotoxicosis (29,30). Color-Doppler ultrasonography reveals rich vascularity and increased flow, which are correlated with the degree of thyroid hyperfunction. Among patients with Graves' thyrotoxicosis, blood flow in the thyroid artery may be higher in those patients who subsequently have recurrent thyrotoxicosis than in those who remain euthyroid after antithyroid drug therapy is discontinued (31). In contrast, blood flow is decreased in patients with exogenous thyrotoxicosis, allowing rapid distinction between them and patients with Graves' disease (32). Among patients with amiodarone-induced thyrotoxicosis, color-Doppler ultrasonography may distinguish between those with iodine-induced thyrotoxicosis (type I), in whom thyroid vascularity is abundant, and those with thyroiditis (type II), in whom the thyroid is avascular and in whom glucocorticoid treatment is effective (see section on effect of excess iodine in Chapter 11) (33). Subacute granulomatous thyroiditis results in thyroid enlargement and areas of hypoechogenicity, probably related to areas that are affected by the inflammatory process (34), and vascularity is decreased (35). With recovery, size decreases, but areas of hypoechogenicity may be detected for many months (34). Color-Doppler ultrasonography distinguishes patients with the multinodular variant of Graves' disease (extra nodular diffuse hypoechogenicity with increased color Doppler signal and maximal peak systolic velocity) from those with nonautoimmune toxic multinodular goiter (normal extranodular vascularity) (36).

Multinodular Goiter

Multinodular goiters are usually larger than diffuse goiters, and 10% to 20% have a substernal or intrathoracic extension that cannot be visualized by ultrasonography because the bony thorax prevents penetration of sound waves (37). The echographic structure of multinodular goiters may be heterogeneous without well-defined nodules, or there may be multiple nodules interspersed throughout a normal appearing gland. Areas of hemorrhage, necrosis, and calcifications are often seen. These goiters, as noted above, may be diffusely hypoechogenic and therefore difficult to distinguish from goitrous autoimmune thyroiditis.

The majority of patients evaluated for a solitary nodule have additional small thyroid nodules detected by ultrasonography (37). The echogenicity of the nodules varies from hyper- to iso- to hypoechoic, often even in the same patient. The presence of multiple nodules, as detected by ultrasonography or any other imaging procedure, does not exclude carcinoma, and indeed it is just as likely to be present in a multinodular goiter as in a solitary nodule (38,39). Therefore, especially in view of the increasing use of nonsurgical treatment for multinodular goiter (see Chapter 69) (37,40), fine-needle aspiration biopsy is usually indicated, especially in euthyroid patients with a dominant or a growing nodule. Ultrasound guidance is recommended because it facilitates sampling of nodular lesions and is associated with a lower rate of false-negative results (see Chapter 73) (41).

Thyroid Cysts

Thyroid cysts are well-defined areas with greatly reduced or no echogenicity (Fig. 16.4), but there may be a few echoes if the cyst contains debris or necrotic tissue. True simple cysts are rare (perhaps 1% of all nodules) and virtually always benign (37). More often, cysts are complex or mixed, with both cystic and solid components. A complex cyst is as likely to be a carcinoma as is a solid nodule (39,42), and the risk of initial nondiagnostic cytology is largely predicted by the presence of a cystic component of the nodule (43). After ultrasound-guided aspiration, the residual solid component should be examined via biopsy (Fig. 16.4). If the cytology is benign and the cyst recurs, as it does in approximately 50% of patients (44), ultrasound-guided treatment can be offered. Injection of tetracycline is not effective in preventing further recurrence (45), but injection of ethanol may be effective (46). The presence of only benign cells in the cystic component of a complex nodule cannot be taken as evidence that the solid component is not a carcinoma, nor can the color of the cyst fluid (42,47).

FIGURE 16.4. Transverse sonogram of a right thyroid nodule with a central cystic region before (A) and after aspiration of the cyst (B). More solid tissue is seen after the aspiration, and it should be biopsied to reduce the likelihood of overlooking carcinoma.

Benign Thyroid Nodules

Most benign thyroid nodules (thyroid adenomas, hyperplastic nodules) are hypoechoic relative to normal thyroid tissue, but so are thyroid carcinomas, and the two cannot be distinguished reliably on the basis of size, degree of echogenicity, or presence of a sonographic halo, calcifications, or vascularization (48,49,50). Therefore, it has been argued that the most cost-effective investigation of these patients is fine-needle aspiration biopsy guided by palpation, and this is the usual practice in many places (3). In Europe, however, most thyroidologists prefer ultrasound-guided biopsy (4), which slightly increases the likelihood of obtaining a sufficient sample (41).

The frequent detection of nonpalpaple nodules or incidentalomas raises the same concern about possible malignancy as when the nodule is palpable. The risk of carcinoma in a nonpalpable nodule found in patients who have not had head or neck irradiation varies from 0.13% to 0.45% (19). In case of suspicion of carcinoma, or if the nodule is at least 1 cm in diameter, fine-needle aspiration biopsy guided by ultrasonography is recommended (3,19,41). Carcinoma is just as common in nonpalpable nodules that are at least 1 cm in diameter as it is in palpable nodules of this size (51).

Interventional ultrasonography is being increasingly used as a nonsurgical therapeutic tool for percutaneous ablation of symptomatic benign nodules, e.g. ethanol injection (52) or interstitial laser photocoagulation (Fig. 16.5) (53).

FIGURE 16.5. Longitudinal sonogram of a hypoechoic left thyroid nodule obtained during laser photocoagulation showing the needle tract and a roughly cylindrical hyperechoic area centrally in the nodule. A needle with a stylet is positioned centrally in the nodule, the stylet is removed, and a quartz laser fiber is inserted throught the needle into the nodule. Laser energy from an infrared laser power source is then delivered through the fiber to destroy the nodule.

Thyroid Carcinomas

Most thyroid carcinomas are hypoechoic, as compared with normal thyroid tissue, and microcalcifications are often present, especially in papillary carcinomas (7,8,14). Excluding microcalcifications, there are no sonographic differences among the different types of thyroid carcinoma or between thyroid carcinomas and benign thyroid nodules. Some vascular patterns recorded by color-Doppler or power-Doppler ultrasonography are suggestive of carcinoma, but the only ultrasound findings that are highly suggestive of carcinoma are invasion of adjacent structures and lymph node enlargement (14). The newly introduced contrast agents for ultrasonography may provide complementary information to differentiate benign from malignant nodules but cannot replace fine-needle aspiration biopsy (54).

Because nodules 2 to 3 mm in diameter can be detected, ultrasonography is increasingly used in the follow-up of patients treated for thyroid carcinoma or at risk for it because of previous irradiation (e.g., after the nuclear accident at Chernobyl). The presence of hypoechoic masses in the thyroid bed or adjacent tissues suggests recurrent carcinoma (see section on radioiodine and other treatments and outcomes in Chapter 70) (8).

COMPUTED TOMOGRAPHY

Computed tomography offers excellent anatomic resolution because of its ability to identify small differences in density between different tissues. Differences in density as small as 0.5% can be detected, as compared with 5% to 10% for conventional X-ray techniques. It is the ability to detect accurately the absorption of X-rays by tissues (attenuation) that enables individual tissues to be identified (6,7).

Computed tomography is highly sensitive for detecting thyroid nodules, but as with ultrasonography, benign nodules cannot be distinguished from carcinomas (7,55,56). It can distinguish solid from simple and complex cysts. Thyroid volume can be determined with an accuracy of approximately 88% (57). It is superior to ultrasonography in detecting thyroid tissue in the retrotracheal, retroclavicular, and intrathoracic regions (58), and it is not as observer dependent as is ultrasonography. The limitations of CT are cost, limited availability for studying patients with thyroid disease, length of the procedure, need for patient cooperation, artifacts caused by swallowing or breathing, and exposure to ionizing irradiation (1 to 4 rad) (7,55,56). The image is not dynamic and, although possible, CT-guided biopsy is more cumbersome than is ultrasound-guided biopsy (59). Patients with nodular goiter who are to undergo CT should not be given a radiographic contrast agent as part of the procedure because of the risk of iodine-induced thyrotoxicosis (Table 16.1) (60).

Computed tomography depends on the attenuation of an X-ray beam as it passes through tissues. The extent of attenuation depends on the constituents of the tissue, and the brightness of each portion (pixel) of the final image is proportional to the degree that it attenuates the X-rays passing through it. The image is usually depicted in shades of gray. Density values are expressed in CT numbers (Hounsfield units), which are related to the attenuation value of water. The thyroid is readily seen on CT because of its high iodine content, and the CT density of the thyroid is closely correlated with its iodine content and can be used to estimate it (61).

The Normal Thyroid Gland

The normal thyroid gland is easily seen on CT, and its density is always higher than that of the surrounding tissues. Differences in density reported from various countries are due to differences in iodine intake. There is no sex difference in density, but it decreases with age and as a consequence of T4 treatment (62), and it increases after intravenous administration of a radiographic contrast agent.

Disease in the thyroid often leads to decreased ability to concentrate iodine or rapid iodine turnover; therefore, reduced density on CT is the hallmark of many thyroid diseases (7,55,56). Exact density measurements, however, have not proven useful in distinguishing between the different diseases. Thus, the CT image may be compatible with a certain diagnosis but is rarely specific for it (56).

Diffuse Thyroid Disease

Nonautoimmune nontoxic diffuse goiters appear as homogeneously enlarged thyroid glands with a varying degree of hypodensity. In patients with Graves' thyrotoxicosis, the density is decreased by 50% to 70% due to decreased iodine stores, and the tissue may be slightly inhomogeneous (63,64). In patients with goitrous autoimmune thyroiditis, the density is reduced in an inhomogeneous pattern and is lowest in patients with hypothyroidism, and increasing goiter size is characteristically associated with decreasing density (65,66). Asymmetric low-density areas should raise the suspicion of lymphoma or carcinoma (66,67).

Subacute thyroiditis is also characterized by focal or diffuse low density (68). In the initial phases acute suppurative thyroiditis has no characteristic CT image, but as infection progresses loculated hypodense abscesses may appear (68).

Multinodular Goiter

Multinodular goiters usually are seen as an enlarged asymmetric thyroid gland with multiple areas of low density of varying degrees of discreteness (Fig. 16.6) (63). The density increases after intravenous administration of a radiographic contrast agent, except in areas of hemorrhage or necrosis or in cysts (66). Calcifications are seen in up to 50% of these goiters. Compression of the trachea, esophagus, and great vessels is easily detected, and CT is ideal for estimating the extent of tracheal compression by a goiter and intrathoracic extension of a goiter (58). In a patient with an intrathoracic mass, CT showing anatomic continuity of the mass with the cervical thyroid and CT density greater than muscle provide evidence of the thyroidal origin of the mass. Mediastinal lymphomas, thymomas, or lymphadenopathy usually have markedly lower CT density (62).

FIGURE 16.6. Computed tomography of a large intrathoracic goiter. Lateral dislocation and compression of the trachea are evident.

Thyroid Cysts

Simple cysts are hypodense lesions, are smooth walled, and are surrounded by normal thyroid tissue. The density of cyst fluid is always less than muscle, and it does not increase after administration of a radiographic contrast agent. Complex cysts are easily distinguished from simple cysts (55,66).

Benign Thyroid Nodules and Carcinomas

Thyroid adenomas and other benign nodules are usually round or oval lesions of low density, and, as noted above, thyroid adenomas or other benign nodules cannot be distinguished from carcinomas using CT when the lesion is confined to the thyroid. Focal calcifications are seen in approximately 10% of benign nodules (7,55,66). Invasive growth into surrounding structures and metastases to cervical lymph nodes are indicative of carcinoma (69).

Papillary and follicular carcinomas are usually seen as irregular low-density masses, and punctate calcifications are present in approximately 60%. There may be slight enhancement after contrast injection. Medullary thyroid carcinomas characteristically appear as single or multiple low-density lesions of variable size in one or both lobes (55,66). Calcification is less often seen than in papillary carcinomas. Patients with C-cell hyperplasia have normal CT scans (70).

Large irregular masses of low attenuation with central cystic or necrotic areas are suggestive of anaplastic carcinoma, especially if many calcifications are seen, but some multinodular goiters have the same appearance. Invasion of the trachea, cricoid or thyroid cartilage, and growth into the tracheal lumen are highly suggestive of anaplastic carcinoma. Both goitrous autoimmune thyroiditis and thyroid lymphoma appear as masses of low to intermediate density with little enhancement after contrast injection (71).

Computed tomography is of value in the follow-up of patients with thyroid carcinoma because of its sensitivity for detecting recurrent carcinoma in the neck and metastases elsewhere. Recurrent carcinoma appears as discrete low-density lesions within or outside the thyroid bed. Lymph node metastases typically have a regular rim and a core of central lucency and no enhancement after contrast injection (69). The ability of CT to detect recurrent thyroid carcinoma is not related to the ability of the tumor to take up radioiodine. Therefore, CT complements whole-body scintigraphy in the follow-up of these patients (see Chapter 12).

Developmental Abnormalities

Scintigraphy and not CT is the imaging procedure of choice when thyroid tissue is being sought anywhere (72). The exception is fetuses, in whom ultrasonography is the preferred procedure (10,73).

Ectopic thyroid tissue may be located anywhere from the foramen cecum at the base of the tongue to the anterior mediastinum. Although radioiodine or pertechnetate scintigraphy can uniquely identify tissue as being of thyroid origin, CT can aid in localization if radionuclide uptake is poor (74). Figure 16.7 shows a CT image of an unusual intratracheal location of ectopic thyroid tissue (74).

FIGURE 16.7. Computed tomography showing slightly enlarged thyroid lobes and ectopic thyroid tissue located within the trachea.

MAGNETIC RESONANCE IMAGING

MRI offers excellent anatomic resolution and generation of images in multiple planes. The technique is highly sensitive but just as nonspecific as ultrasonography and CT in differentiating benign thyroid nodules from carcinomas. It can distinguish solid from simple and complex cysts (7,55,56). Like CT it provides highly accurate estimates of thyroid volume and is useful especially in irregularly enlarged goiters. For this purpose, the observer variation of MR imaging is 2% to 4% (75,76). Like CT, and in contrast to ultrasonography, it can identify thyroid tissue in the retrotracheal, retroclavicular, and intrathoracic regions (77). The paramagnetic contrast agent gadolinium allows visualization of tumor vascularity (78). The limitations of MRI are its cost, limited availability for studying patients with thyroid disease, length of the procedure, need for patient cooperation (5% to 10% of patients cannot tolerate it due to claustrophobia, and some, especially children, need to be sedated) (79). Patient and tissue movement (e.g., swallowing) decreases image quality, and calcifications are better seen with CT (80,81). MRI cannot be used in patients with cardiac pacemakers, implantable defibrillators, CNS aneurysmal clips, cochlear implants, and ferromagnetic ocular fragments. Small metal objects, stainless steel surgical clips, and orthopedic devices decrease resolution and cause field inhomogeneity, but do not hinder MR imaging. Dental substances, if ferromagnetic, cause image distortion (Table 16.1).

Magnetic resonance images depend on the magnetic properties of certain atomic nuclei. Protons have a positive electrical charge and generate a magnetic field as they spin. The protons can be excited using a radiofrequency pulse, lifting some of the protons to a higher energy state. When radiofrequency is turned off, the protons realign themselves with the static external magnetic field through a process called relaxation. The resulting realignment results in protons returning to a lower energy state and the release of energy as a small voltage. This voltage is detected by the surface coil receiver, relayed to a computer, and reconstructed into an image. The MRI signal contains several variable components. The T1 relaxation time (longitudinal or spin-lattice relaxation time) reflects the time for protons to give up their energy to the surrounding environment (lattice) and return to their original alignment parallel to the magnetic field. The T2 relaxation time (transverse or spin-spin relaxation time) is the time needed for synchronous transverse spinning to decay after excitation. Adjustment of the pulse sequence can favor one or the other of these magnetic properties. As a rule, T1-weighted transverse images are initially obtained from cranial to caudal. Coronal scans allow the evaluation of substernal goiters (82,83). Subsequently, T2-weighted images are obtained. These require longer scan times and are more dependent on patient cooperation.

The Normal Thyroid Gland

On T1-weighted images the normal thyroid gland has a nearly homogeneous signal with an intensity similar to that of the adjacent neck muscles (Fig. 16.8A) (79,80,81,82,83). Air, blood, and vessels usually appear black. On T2-weighted images, the normal thyroid has a greater signal intensity than the adjacent muscles (Fig. 16.8B). Blood vessels, lymph nodes, fat, and muscle are clearly identified and distinguished from the thyroid. As with ultrasonography and CT, small solitary or multiple focal abnormalities of the thyroid are seen in up to nearly 50% of normal subjects (84). Normal parathyroid glands cannot be seen, but enlarged ones can (85). MRI, like ultrasonography and CT, detects parathyroid adenomas with a sensitivity of 60% to 80% (85,86).

FIGURE 16.8. T1-weighted (A) and T2-weighted (B) MRIs of a normal thyroid gland.

Diffuse Thyroid Disease

In Graves' disease both T1- and T2-weighted images show a diffusely increased but slightly heterogeneous signal (87,88). There is a linear relationship between the thyroid:muscle signal ratio and serum T4 concentrations and 24-hour thyroid radioiodine uptake values (87). After treatment with radioiodine, this signal ratio decreases, concomitant with the decrease in serum T4 concentrations (87).

The thyroid in patients with goitrous autoimmune thyroiditis is heterogeneous on T1-weighted images and has a diffusely increased signal on T2-weighted images, and there may be linear bands of increased intensity. These bands are thought to reflect areas of fibrosis (89). Infiltration of adjacent neck structures and hypointensity on T1- and T2-weighted images are suggestive of Riedel's thyroiditis (90).

Multinodular Goiter

MRI can detect nodules as small as 3 to 5 mm (55). Characteristically, multinodular goiters have various degrees of heterogeneity and low to increased signal intensity on T1-weighted images (Fig. 16.9) (82). Focal hemorrhage and cystic degeneration are characterized by high signal intensity (89). T2-weighted images show more pronounced heterogeneity and increased intensity (82). Nodules are better visualized on T2-weighted images (89). The MR characteristics of hypo- or hyperfunctioning nodules do not differ.

FIGURE 16.9. T1-weighted sagittal MRI of a large multinodular goiter extending into the thorax.

Thyroid Cysts

Simple cysts have a homogeneous high-intensity signal on both T1- and T2-weighted imaging (79). The intensity on T1-weighted images increases with increasing protein and lipid content.

Benign Thyroid Nodules and Carcinomas

Thyroid adenomas and other benign nodules appear round or oval with a heterogeneous signal equal to or greater than that of normal thyroid tissue (82,87). On T2-weighted images the nodules have increased signal intensity. No MRI characteristics accurately distinguish between benign nodules and carcinomas, although benign nodules characteristically have a smoother, more uniform, and thicker capsule than carcinomas. Thyroid carcinomas appear as focal or nonfocal lesions of variable size; they are isointense or slightly hyperintense on T1-weighted images and hyperintense on T2-weighted images. The imaging characteristics of all types of thyroid carcinomas including medullary carcinoma and lymphoma are similar (71,83,89).

The extent of thyroid carcinoma can be determined preoperatively, which may be useful in planning surgery. Extension into adjacent structures (such as muscles, vessels, the larynx, and the trachea) is usually evident. MRI cannot distinguish metastatic from inflammatory adenopathy. An important application of MRI is for the detection of recurrent carcinoma. Although the thyroid remnant is usually seen as peritracheal tissue with low signal intensity on T1- and T2-weighted images, recurrent carcinoma and lymph node metastases have low to medium signal intensity on T1-weighted images and medium to high signal intensity on T2-weighted images (82). Features such as asymmetry, increased signal intensity in the thyroid bed, and invasion or displacement of adjacent tissue, as well as enlarged lymph nodes with increased signal intensity, thus suggest recurrent carcinoma (7,56,91). Gadolinium injection may be useful because metastatic nodes are enhanced centrally after gadolinium injection (78). Furthermore, recurrent carcinoma enhances with gadolinium, whereas scar tissue usually does not (78). However, in the differentiation between benign and malignant thyroid tumors the time-intensity curves after gadolinium injection overlap in benign and malignant nodules (92).

CONCLUSION

There is no absolute clinical indication for performing any of the imaging procedures described herein, and none of them accurately distinguish benign thyroid nodules from thyroid carcinomas. Nonetheless, these procedures, particularly ultrasonography, are being increasingly used (4,8). Ultrasonography is widely available, it costs relatively little, and many physicians have found it of value in patients with several different thyroid disorders (4,9,37,93). Even if it cannot reliably identify or exclude thyroid carcinoma, it provides superior morphologic detail, as compared with scintigraphy, and allows more accurate placing of needles for biopsy and therapy (9,37). Additionally, it provides far more accurate estimates of thyroid volume than does palpation, and some have found the information about echogenicity and vascularization provided by ultrasonography to be useful in the classification and follow-up of patients with thyroid disorders.

CT and MRI provide information similar to that provided by ultrasonography. Their greater expense and more limited availability argue against their use, with rare exceptions. CT is valuable in determining the extent of a substernal goiter or in the evaluation of a mediastinal mass. It can give valuable information in the evaluation of thyroid carcinoma and its spread. MRI is useful in the same clinical situations and may be superior to CT in the evaluation of patients suspected of having recurrent carcinoma, be it in the thyroid bed or in regional lymph nodes.

REFERENCES

1. Ortiz R, Hupart KH, DeFesi CR, et al. Effect of early referral to an endocrinologist on efficiency and cost of evaluation and development of treatment plan in patients with thyroid nodules. J Clin Endocrinol Metab 1998;83:3803.

2. Jarlov AE, Nygaard B, Hegedus L, et al. Observer variation in the clinical and laboratory evaluation of patients with thyroid dysfunction and goiter. Thyroid 1998;8:393.

3. Singer PA, Cooper DS, Daniels GH, et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 1996;156:2165.

4. Bennedbaek FN, Perrild H, Hegedus L. Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey. Clin Endocrinol (Oxf) 1999;50:357.

5. Bennedbaek FN, Hegedus L. Management of the solitary thyroid nodule: results of a North American survey. J Clin Endocrinol Metab 2000;85:2493.

6. Nusynowitz ML. Thyroid imaging. Lippincott's Prim Care Pract 1999;3:546.

7. Naik KS, Bury RF. Imaging the thyroid. Clin Radiol 1998;53: 630.

8. Solbiati L, Osti V, Cova L, et al. Ultrasound of thyroid, parathyroid glands and neck lymph nodes. Eur Radiol 2001;11: 2411.

9. Hegedus L. Thyroid ultrasound. Endocrinol Metab Clin North Am 2001;30:339.

10. Achiron R, Rotstein Z, Lipitz S, et al. The development of the foetal thyroid: in utero ultrasonographic measurements. Clin Endocrinol (Oxf) 1998;48:259.

11. Jarlov AE, Nygard B, Hegedus L, et al. Observer variation in ultrasound assessment of the thyroid gland. Br J Radiol 1993;66: 625.

12. Gotway MB, Higgins CB. MR imaging of the thyroid and parathyroid glands. Magn Reson Imaging Clin N Am 2000;8:163.

13. Gritzmann N, Koischwitz D, Rettenbacher T. Sonography of the thyroid and parathyroid glands. Radiol Clin North Am 2000; 38:1131.

14. Cerbone G, Spiezia S, Colao A, et al. Power Doppler improves the diagnostic accuracy of color Doppler ultrasonography in cold thyroid nodules: follow-up results. Horm Res 1999;52:19.

15. Correas JM, Bridal L, Lesavre A, et al. Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts. Eur Radiol 2001;11:1316.

16. Maiorana R, Carta A, Floriddia G, et al. Thyroid hemiagenesis: prevalence in normal children and effect on thyroid function. J Clin Endocrinol Metab 2003;88:1534.

17. Gupta P, Maddalozzo J. Preoperative sonography in presumed thyroglossal duct cysts. Arch Otolaryngol Head Neck Surg 2001; 127:200.

18. Ying M, Brook F, Ahuja A, et al. The value of thyroid parenchymal echogenicity as an indicator of pathology using the sternomastoid muscle for comparison. Ultrasound Med Biol 1998; 24:1097.

19. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226.

20. Knudsen N, Bulow I, Jorgensen T, et al. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative epidemiological study in two regions with slightly different iodine status. Clin Endocrinol (Oxf) 2000;53:479.

21. Brunn J, Block U, Ruf G, et al. Volumetric analysis of thyroid lobes by real-time ultrasound [author's transl]. Dtsch Med Wochenschr 1981;106:1338.

22. Hegedus L, Perrild H, Poulsen LR, et al. The determination of thyroid volume by ultrasound and its relationship to body-weight, age, and sex in normal subjects. J Clin Endocrinol Metab 1983;56:260.

23. Schlogl S, Werner E, Lassmann M, et al. The use of three-dimensional ultrasound for thyroid volumetry. Thyroid 2001;11: 569.

24. Hegedus L. Thyroid size determined by ultrasound. Influence of physiological factors and non-thyroidal disease. Dan Med Bull 1990;37:249.

25. Delange F, Benker G, Caron P, et al. Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency. Eur J Endocrinol 1997; 136:180.

26. Pedersen OM, Aardal NP, Larssen TB, et al. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 2000;10:251.

27. Raber W, Gessl A, Nowotny P, et al. Thyroid ultrasound versus antithyroid peroxidase antibody determination: a cohort study of four hundred fifty-one subjects. Thyroid 2002;12:725.

28. Matsuzuka F, Miyauchi A, Katayama S, et al. Clinical aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases. Thyroid 1993;3:93.

29. Vitti P, Rago T, Mancusi F, et al. Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves' disease. Acta Endocrinol (Copenh) 1992;126:128.

30. Zingrillo M, D'Aloiso L, Ghiggi MR, et al. Thyroid hypo echogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence? Clin Endocrinol (Oxf) 1996;45:201.

31. Baldini M, Castagnone D, Rivolta R, et al. Thyroid vascularization by color doppler ultrasonography in Graves' disease. Changes related to different phases and to the long-term outcome of the disease. Thyroid 1997;7:823.

32. Bogazzi F, Bartalena L, Vitti P, et al. Color flow Doppler sonography in thyrotoxicosis factitia. J Endocrinol Invest 1996;19:603.

33. Bogazzi F, Bartalena L, Brogioni S, et al. Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. Thyroid 1997;7:541.

34. Bennedbaek FN, Hegedus L. The value of ultrasonography in the diagnosis and follow-up of subacute thyroiditis. Thyroid 1997;7:45.

35. Hiromatsu Y, Ishibashi M, Miyake I, et al. Color Doppler ultrasonography in patients with subacute thyroiditis. Thyroid 1999;9:1189.

36. Boi F, Loy M, Piga M, et al. The usefulness of conventional and echo colour Doppler sonography in the differential diagnosis of toxic multinodular goitres. Eur J Endocrinol 2000;143:339.

37. Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003;24:102.

38. Tollin SR, Mery GM, Jelveh N, et al. The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter. Thyroid 2000;10:235.

39. Belfiore A, La Rosa GL, La Porta GA, et al. Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med 1992;93:363.

40. Hermus AR, Huysmans DA. Treatment of benign nodular thyroid disease. N Engl J Med 1998;338:1438.

41. Danese D, Sciacchitano S, Farsetti A, et al. Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules. Thyroid 1998;8:15.

42. Abbas G, Heller KS, Khoynezhad A, et al. The incidence of carcinoma in cytologically benign thyroid cysts. Surgery 2001;130: 1035.

43. Alexander EK, Heering JP, Benson CB, et al. Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules. J Clin Endocrinol Metab 2002;87:4924.

44. Monzani F, Lippi F, Goletti O, et al. Percutaneous aspiration and ethanol sclerotherapy for thyroid cysts. J Clin Endocrinol Metab 1994;78:800.

45. Hegedus L, Hansen JM, Karstrup S, et al. Tetracycline for sclerosis of thyroid cysts. A randomized study. Arch Intern Med 1988;148:1116.

46. Bennedbaek FN, Hegedus L. Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind controlled trial. J Clin Endocrinol Metab 2003;88:5773.

47. McHenry CR, Slusarczyk SJ, Khiyami A. Recommendations for management of cystic thyroid disease. Surgery 1999;126: 1167.

48. Giuffrida D, Gharib H. Controversies in the management of cold, hot, and occult thyroid nodules. Am J Med 1995;99:642.

49. Rago T, Vitti P, Chiovato L, et al. Role of conventional ultrasonography and color flow-Doppler sonography in predicting malignancy in ‘cold’ thyroid nodules. Eur J Endocrinol 1998; 138:41.

50. Hegedus L, Karstrup S. Ultrasonography in the evaluation of cold thyroid nodules. Eur J Endocrinol 1998;138:30.

51. Hagag P, Strauss S, Weiss M. Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules. Thyroid 1998;8:989.

52. Bennedbaek FN, Karstrup S, Hegedus L. Percutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases. Eur J Endocrinol 1997;136:240.

53. Dossing H, Bennedbaek FN, Karstrup S, et al. Benign solitary solid cold thyroid nodules: US-guided interstitial laser photocoagulation—initial experience. Radiology 2002;225:53.

54. Spiezia S, Farina R, Cerbone G, et al. Analysis of color Doppler signal intensity variation after levovist injection: a new approach to the diagnosis of thyroid nodules. J Ultrasound Med 2001; 20:223.

55. Youserm DM, Huang T, Loevner LA, et al. Clinical and economic impact of incidental thyroid lesions found with CT and MR. AJNR Am J Neuroradiol 1997;18:1423.

56. Loevner LA. Imaging of the thyroid gland. Semin Ultrasound CT MR 1996;17:539.

57. Hermans R, Bouillon R, Laga K, et al. Estimation of thyroid gland volume by spiral computed tomography. Eur Radiol 1997; 7:214.

58. Jennings A. Evaluation of substernal goiters using computed tomography and MR imaging. Endocrinol Metab Clin North Am 2001;30:401.

59. DelGaudio JM, Dillard DG, Albritton FD, et al. Computed tomography—guided needle biopsy of head and neck lesions. Arch Otolaryngol Head Neck Surg 2000;126:366.

60. Shimura H, Takazawa K, Endo T, et al. T4-thyroid storm after CT-scan with iodinated contrast medium. J Endocrinol Invest 1990;13:73.

61. Imanishi Y, Ehara N, Shinagawa T, et al. Correlation of CT values, iodine concentration, and histological changes in the thyroid. J Comput Assist Tomogr 2000;24:322.

62. Reede DL, Bergeron RT, McCauley DI. CT of the thyroid and of other thoracic inlet disorders. J Otolaryngol 1982;11:349.

63. Silverman PM, Newman GE, Korobkin M, et al. Computed tomography in the evaluation of thyroid disease. AJR Am J Roentgenol 1984;142:897.

64. Kamijo K. Clinical studies on thyroid CT number in Graves' disease and destructive thyrotoxicosis. Endocr J 1994;41:25.

65. Kamijo K. Clinical studies on thyroid CT number in chronic thyroiditis. Endocr J 1994;41:19.

66. Weber AL, Randolph G, Aksoy FG. The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. Radiol Clin North Am 2000;38:1105.

67. Kim HC, Han MH, Kim KH, et al. Primary thyroid lymphoma: CT findings. Eur J Radiol 2003;46:233.

68. Bernard PJ, Som PM, Urken ML, et al. The CT findings of acute thyroiditis and acute suppurative thyroiditis. Otolaryngol Head Neck Surg 1988;99:489.

69. Van den Brekel MW. Lymph node metastases: CT and MRI. Eur J Radiol 2000;33:230.

70. Wells SA Jr., Donis-Keller H. Current perspectives on the diagnosis and management of patients with multiple endocrine neoplasia type 2 syndromes. Endocrinol Metab Clin North Am 1994;23:215.

71. Takashima S, Nomura N, Noguchi Y, et al. Primary thyroid lymphoma: evaluation with US, CT, and MRI. J Comput Assist Tomogr 1995;19:282.

72. Meller J, Becker W. The continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound. Eur J Nucl Med Mol Imaging 2002;29[Suppl 2]:S425.

73. Polk DH. Diagnosis and management of altered fetal thyroid status. Clin Perinatol 1994;21:647.

74. Dossing H, Jorgensen KE, Oster-Jorgensen E, et al. Recurrent pregnancy-related upper airway obstruction caused by intratracheal ectopic thyroid tissue. Thyroid 1999;9:955.

75. Bonnema SJ, Andersen PB, Knudsen DU, et al. MR imaging of large multinodular goiters: observer agreement on volume versus observer disagreement on dimensions of the involved trachea. AJR Am J Roentgenol 2002;179:259.

76. Huysmans DA, de Haas MM, van den Broek WJ, et al. Magnetic resonance imaging for volume estimation of large multi nodular goitres: a comparison with scintigraphy. Br J Radiol 1994;67:519.

77. Newman E, Shaha AR. Substernal goiter. J Surg Oncol 1995; 60:207.

78. Crawford SC, Harnsberger HR, Lufkin RB, et al. The role of gadolinium-DTPA in the evaluation of extracranial head and neck mass lesions. Radiol Clin North Am 1989;27:219.

79. Gefter WB, Spritzer CE, Eisenberg B, et al. Thyroid imaging with high-field-strength surface-coil MR. Radiology 1987;164: 483.

80. Baker HL Jr, Berquist TH, Kispert DB, et al. Magnetic resonance imaging in a routine clinical setting. Mayo Clin Proc 1985; 60:75.

81. Stark DD, Clark OH, Moss AA. Magnetic resonance imaging of the thyroid, thymus, and parathyroid glands. Surgery 1984;96: 1083.

82. Higgins CB, McNamara MT, Fisher MR, et al. MR imaging of the thyroid. AJR Am J Roentgenol 1986;147:1255.

83. Higgins CB, Auffermann W. MR imaging of thyroid and parathyroid glands: a review of current status. AJR Am J Roent genol 1988;151:1095.

84. Funari M, Campos Z, Gooding GA, et al. MRI and ultrasound detection of asymptomatic thyroid nodules in hyperparathyroidism. J Comput Assist Tomogr 1992;16:615.

85. Seelos KC, DeMarco R, Clark OH, et al. Persistent and recurrent hyperparathyroidism: assessment with gadopentetate dimeglumine-enhanced MR imaging. Radiology 1990;177: 373.

86. Karstrup S. Ultrasonically guided localization, tissue verification, and percutaneous treatment of parathyroid tumours. Thesis. Dan Med Bull 1995;42:175.

87. Charkes ND, Maurer AH, Siegel JA, et al. MR imaging in thyroid disorders: correlation of signal intensity with Graves' disease activity. Radiology 1987;164:491.

88. Tezuka M, Murata Y, Ishida R, et al. MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy. J Magn Reson Imaging 2003;17: 163.

89. Noma S, Nishimura K, Togashi K, et al. Thyroid gland: MR imaging. Radiology 1987;164:495.

90. Perez Fontan FJ, Cordido CF, Pombo FF, et al. Riedel thyroiditis: US, CT, and MR evaluation. J Comput Assist Tomogr 1993; 17:324.

91. Takashima S, Takayama F, Wang J, et al. Using MR imaging to predict invasion of the recurrent laryngeal nerve by thyroid carcinoma. AJR Am J Roentgenol 2003;180:837.

92. Kusunoki T, Murata K, Nishida S, et al. Histopathological findings of human thyroid tumors and dynamic MRI. Auris Nasus Larynx 2002;29:357.

93. Brennan MD, Miner KM, Rizza RA. Profiles of the Endocrine Clinic: the Mayo Clinic. J Clin Endocrinol Metab 1998;83: 3427.