6.2.1 Ultrasound

Over the past 4 decades, US has become the preferred diagnostic imaging tool for evaluating thyroid disease. The gland’s superficial location in the anterior neck and the high imaging resolution of modern transducers make US an ideal tool for thyroid imaging. US provides an accurate assessment of gland size and parenchymal homogeneity without the adverse effects of ionizing radiation or the high costs of other imaging modalities. The most frequent indications for thyroid US evaluation include a palpable neck mass in the visceral space, an incidental thyroid abnormality detected by other imaging modalities (such as CT and MRI), screening high-risk patients for occult malignancy, evaluating for regional nodal metastases in patients with suspected or proven thyroid carcinoma prior to thyroidectomy, and screening the thyroid bed in postthyroidectomy patients. ^{2 , 3}

US examination employs a linear-array, high-frequency 7.5 to 15 MHz transducer, with the neck in hyperextension. Each lobe of the thyroid is imaged in longitudinal and transverse planes using both B mode and color Doppler US. The average adult thyroid measures 4 to 6 cm in craniocaudal length and 1.3 to 1.8 cm in anteroposterior and transverse dimensions. The normal anteroposterior thickness of the isthmus is up to 3 mm. ⁴ The normal thyroid has a homogeneous background of medium-level to high-level echogenicity (uniformly hyperechoic relative to the adjacent strap muscles) surrounded by an echogenic fibrous capsule. The thyroid capsule allows for clear delineation of the thyroid from adjacent structures of the visceral space (Fig. 6.1 a). Color Doppler imaging may be used to evaluate the vascularity of the thyroid as well as thyroid nodules, which may be helpful in determining malignancy. The routine thyroid US also evaluates the normal adjacent anatomical structures of the visceral neck, such as the common carotid arteries, jugular veins, cervical esophagus, parathyroid glands, and lymph nodes. Familiarity with the normal sonographic appearance of these adjacent structures may prevent misinterpretation of normal anatomical structures as thyroid pathology. Potential limitations of US include the high degree of operator dependence and the inability to adequately evaluate the retrotracheal region and the superior mediastinum. ¹

6.2.2 CT and MRI

CT and MRI have limited ability to directly evaluate intrathyroid pathology due to poor capacity to discriminate benign and malignant disease. However, CT and MRI have important adjunctive roles for staging advanced thyroid cancer by identification of extracapsular extension of disease into adjacent structures, such as the esophagus, trachea, larynx, musculature, and vasculature. They are also important for evaluating direct extension of disease into the mediastinum or retrotracheal region, as well as to identify both regional lymph nodes and distal metastases, providing relevant information that can impact surgical management. They may also have specific roles in cases of multinodular goiter to evaluate for retrosternal extension of disease and tracheal deviation or compression. ^{5 , 6} Due to its high iodine content, the normal thyroid has increased attenuation compared to the adjacent musculature, with a density of 80 to 100 Hounsfield units. ^{4 , 5} Contrast-enhanced CT diffusely increases the attenuation of the thyroid due to strong uptake of iodinated contrast, providing additional information about thyroid lesions (Fig. 6.1 b).

However, iodinated contrast should be avoided if functional nuclear imaging is desired or in the workup of differentiated thyroid carcinoma (unless the information obtained from the addition of contrast is expected to significantly alter the patient’s management) because a large iodine thyroid gland load may persist for up to 6 weeks and interfere with radioactive iodine uptake. As an alternative, MRI with gadolinium may be performed in conjunction with nuclear scintigraphy because gadolinium does not affect iodine uptake or organification by the thyroid.

The thyroid is imaged by MRI using an anterior neurovascular neck coil centered over the thyroid. Multiple pulse sequences can be obtained through the gland, including sagittal and axial T1 precontrast, axial T2 fast spin-echo with fat saturation, and postgadolinium axial and coronal T1 with fat saturation. The thyroid gland is homogeneous in signal and slightly hyperintense compared to neck musculature on T1 imaging. On T2-weighted imaging, the thyroid is homogeneously hyperintense to neck musculature (Fig. 6.1 c). It demonstrates a diffuse homogeneous pattern of enhancement on postcontrast imaging.

6.2.3 Nuclear Scintigraphy

Nuclear scintigraphy plays an important role in the evaluation of thyroid disease, providing a reflection of the functional state of the thyroid gland as well as the physiological state of any structures within the gland, such as a thyroid nodule. Indications for thyroid scintigraphy include evaluation of the size and location of thyroid tissue, thyroid evaluation when clinical laboratory tests suggest abnormal thyroid function, evaluation of patients at risk for thyroid neoplasm, assessment of function of thyroid nodules, and evaluation of congenital thyroid abnormalities.

Thyroid uptake measurements are obtained for differentiation of hyperthyroidism from forms of thyrotoxicosis and for calculating I-131 doses in patients to be treated for hyperthyroidism with thyroid ablative therapy. Whole body imaging is performed to identify the presence and location of residual thyroid tissue after thyroidectomy or ablative therapy for thyroid carcinoma and for identifying iodine avid metastases from thyroid carcinoma. ⁶

The two main isotopes for thyroid scintigraphy are technetium-99m (Tc-99m) pertechnetate and iodine 123 (I-123). Tc-99m pertechnetate is trapped by the thyroid, whereas I-123 is trapped and organified. One distinct advantage of I-123 over Tc-99m is in the evaluation of thyroid nodules, in particular when a thyroid nodule appears “warm” by Tc-99m. If “cold” on I-123, this is considered a discordant nodule requiring further workup and possible thyroid fine-needle aspiration (FNA). I-123 also has an advantage over Tc-99m in identifying and localizing ectopic thyroid tissue because there is significantly less background activity within the head and neck when compared to Tc-99m. ^{5 , 7 , 8} Whether imaged with Tc-99m pertechnetate or I-123, the normal thyroid shows homogeneous radionuclide uptake throughout the gland (Fig. 6.1 d).

Radioactive iodine uptake may be measured at 4 and 24 hours with normal values of 5 to 15% and 8 to 35%, respectively. The use of iodine-containing supplements or certain medications can potentially affect iodine uptake and incorporation by the thyroid gland. Most centers recommend a low-iodine diet for 7 to 14 days prior to radioiodine administration.

6.3.1 Ectopic Thyroid Tissue

Failure or abnormal descent of the thyroid gland along its normal pathway may occur during the fetal period, resulting in ectopic thyroid tissue at any location along the pathway of descent. Clinically apparent thyroid ectopia is rare, occurring in 1 in 3,000 to 1 in 10,000 people; however, autopsy series suggest a much higher prevalence, ranging from 7 to 10%. ^{11 , 12} Although 90% of ectopic thyroid tissue occurs at the tongue base and arises from the median anlage, ectopic thyroid tissue may also be identified in the lateral neck, larynx, esophagus, mediastinum, pericardium, or heart (Fig. 6.2 a). Rare noncervical and nonmediastinal locations of ectopic thyroid tissue have also been described in the gallbladder, porta hepatis, small bowel, pancreas, and adrenal glands. Ectopic thyroid is vulnerable to any disease process that may occur within the normally located thyroid gland; however, development of malignancy is considered rare. When tumor does arise within ectopic thyroid tissue, it is reported as papillary carcinoma in > 90% of cases. ^{12 , 13}

When thyroid ectopia is identified, patients should undergo further evaluation for the presence of normally located thyroid tissue prior to surgical excision of ectopic thyroid, to avoid an acute thyroid insufficiency. Other than lacking the typical bilobed appearance, ectopic thyroid tissue appears as normal thyroid tissue by all imaging modalities. Nuclear scintigraphy demonstrates uptake of radiotracer in the ectopic thyroid as well as in the orthotopic tissue. The most common US imaging finding is the absence of normal orthotopic thyroid tissue. However, careful evaluation of the neck at the tongue base or along the expected track of thyroid descent may reveal a round, well-circumscribed mass identical to the expected echogenicity of normal thyroid tissue. Ectopic thyroid gland detected by noncontrast CT will present as a hyperdense nodular mass with respect to the adjacent musculature, showing intense enhancement after intravenous administration of iodinated contrast. MRI presents thyroid ectopia as a nodular mass, T1 isointense to mildly hyperintense in signal compared to muscle, mildly T2 hyperintense, and with a variable pattern of enhancement on postgadolinium imaging. Detection of nodules or goitrous enlargement in the ectopic thyroid tissue may also increase the diagnostic confidence.

Lingual thyroid is the most common form of thyroid ectopia. ¹⁴ The ectopic tissue at the base of the tongue may range from microscopic to several centimeters (Fig. 6.2 b). Clinical symptoms are often related to growth of the ectopic thyroid tissue, including dysphagia, dysphonia, cough, and foreign body sensation. However, patients may be asymptomatic, with incidental detection by clinical exam or imaging for nonthyroid-related purposes.

6.3.2 Thyroglossal Duct Cyst

Thyroglossal duct (TGD) cyst is the most common midline congenital neck mass, arising secondarily to failure of complete regression of the TGD. ¹⁵ Similarly to ectopic thyroid tissue, a TGD cyst may arise anywhere along the descent pathway of the median anlage, from the base of the tongue to the suprasternal region. Most lesions present in childhood or in young adults as an enlarging painless mass, with 60 to 80% associated with the hyoid bone. Ectopic thyroid tissue within the cyst wall is seen in up to 5.7% of cases. ¹⁶ TGD cysts can be complicated by inflammation and hemorrhage, which may be associated with pain. Carcinoma arising in a TGD cyst is rare, occurring in 0.7 to 1% of TGD cysts, with 90% arising from a thyroid tissue remnant. Papillary carcinoma represents approximately 94% of TGD cyst carcinomas, with < 5% being of squamous cell origin. The average patient age for TGD cyst carcinoma development is 39 years, with the squamous cell type occurring at an average age of 54 years.

US is the modality of choice for initial imaging assessment of a suspected TGD cyst. On US, TGD cysts may have a variable echogenicity pattern based on intrinsic fluid protein content. The most common presentations include a well-circumscribed anechoic cyst or a pseudosolid appearance with a heterogeneous echo pattern (more commonly seen in children). Posterior acoustic enhancement (increased echogenicity deep to the cyst) is a cystic characteristic finding; however, this may be subtle in the setting of a pseudosolid lesion. The presence of thick walls or internal septa often correlates with internal inflammation. CT presents TGD cysts as well-circumscribed, thin-walled midline lesions with mucoid attenuation, usually at or below the level of the hyoid bone (Fig. 6.3 a).

Increased complexity of the lesion, with thickening and enhancement of cyst walls, septations, and increased cyst attenuation, suggests cyst inflammation or infection. TGD cysts may appear on MRI scans as simple cysts, demonstrating low intrinsic T1 and high T2 signal, though intrinsic protein/thyroglobulin content may elicit high T1 and high T2 signal. Identification of a soft tissue nodule within a TGD cyst should raise concern for carcinoma, especially in the presence of calcification (Fig. 6.3 b). The main differential considerations of TGD cysts include a branchial cleft cyst, dermoid, and hemangioma, and an enlarged lymph node.

6.4.1 Graves’ Disease

Graves’ disease is the most common cause of hyperthyroidism in the United States. It is an autoimmune process in which patients develop autoantibodies against thyroid-stimulating hormone (TSH) receptors, thyroglobulin, and thyroperoxidase. TSH receptor antibodies result in receptor stimulation, leading to glandular growth, increased vascularity, and increased production of thyroid hormone. On gray-scale US, the thyroid is enlarged and diffusely hypoechoic; however, normal echogenicity may be present. ^{17 , 18} On color Doppler imaging, the thyroid shows markedly increased vascularity throughout the thyroid parenchyma, resulting in the “thyroid storm” pattern (Fig. 6.4 a,b).

Peak systolic velocity measurements of the inferior thyroid or intraparenchymal arteries are markedly increased in Graves’ disease, which is helpful in distinguishing it from Hashimoto’s disease and thyrotoxicosis. CT and MRI have limited usefulness in evaluation of Graves’ disease, showing an enlarged thyroid with possible visualization of a pyramidal lobe or prominent intrathyroidal vasculature. ¹⁹

Thyroid scintigraphy shows a diffusely enlarged gland with increased thyroid uptake. A pyramidal lobe may also be identified on scintigraphic imaging (Fig. 6.4 c). Radioactive iodine uptake (RAIU) is elevated at 24 hours (> 35%), although a variant form, Graves’ disease with rapid iodine turnover, may show normal RAIU at 24 hours but elevated RAIU at 4 to 6 hours (> 20%). ⁸

An extrathyroidal manifestation of Graves’ disease is thyroid-associated orbitopathy. Its diagnosis is primarily clinical; however, imaging may be performed in uncertain cases. ²⁰ CT and MRI are the primary imaging modalities, classically showing proptosis with expansion of the intraorbital fat and enlargement of the extraocular muscle bellies, but not their tendons. The inferior rectus is most commonly affected, followed by the medial rectus and superior muscle complex. Bilateral involvement occurs in approximately 90% of cases (Fig. 6.4 d).