Deviations during any stage of development may lead to aberrant configurations or heterotopic locations of the thyroid gland. If the thyroglossal duct fails to involute completely, its persistence is a 1 to 3 cm cystic, fluid-filled remnant located anywhere along the route of the duct.⁶ The thyroglossal duct cyst is the most common congenital cyst found in the neck.¹³

The most critical abnormality is the absence of the thyroid gland (athyrosis). This rare condition is associated with cretinism or congenital hypothyroidism. Early identification and intervention with hormone replacement can stave off the physical and mental deficiencies associated with the congenital hypothyroidism.

More commonly, the gland may differentiate into configurations other than an isthmus and two lateral lobes. The variation occurring most often is a pyramidal lobe, which has been identified to some degree in approximately as many as 50% of normal patients.⁵ Developmentally, the pyramidal lobe arises from the caudal portion of the thyroglossal tract. Usually, this lobe is small, extending midline upward from the isthmus, but it can arise from either lobe, more often the left lobe than the right¹² (Fig. 17-3).

Other anatomic variations include the absence of an isthmus with the gland appearing as two independent lobes, the absence of one lobe with enlargement of the remaining lobe, or continuity from one lobe to the other effectively obliterating the isthmus.⁵

Thyroid gland development can occur ectopically at any point along the pathway of descent.¹² A normal gland may also rest entirely above (suprahyoid or prelaryngeal) or below the hyoid bone. Lingual thyroid, although relatively rare (1 in 100,000 cases of thyroid disease), is the most common location for functional ectopic tissue.¹³ This placement is usually identified by an incidental finding of a mass at the back of the tongue.¹⁴

Other ectopic locations include under the tongue (sublingual), the mediastinum (substernal), and rarely
the tracheal or esophageal wall (Fig. 17-4). Small amounts of histologically functioning tissues may also be found along the internal carotid artery, the supraclavicular fossa, adjacent to the aortic arch or between the aorta and the pulmonary trunk, within the upper portion of the pericardium or mediastinum, and even within the interventricular septum.^5,6,15

Many anatomic landmarks help to define the thyroid gland on a sonogram (Fig. 17-5A). On transverse images, the common carotid artery and internal jugular vein form the posterior lateral border of the gland. The artery is located medial to the vein. These structures are distinguished from the thyroid gland by echogenic walls and anechoic centers with color or pulsed wave Doppler imaging also available to assist in clarifying the anatomy. The longus colli muscle appears as a low-level, echogenic structure defining the posterior border of the gland. The air-filled trachea forms the medial border and appears hyperechoic, with posterior shadowing. The sternothyroid, sternohyoid, and omohyoid muscles, collectively called the strap muscles, form the anterolateral border of the gland. The sternothyroid muscle is directly superficial to the thyroid gland and is bordered by the sternohyoid anteriorly and the omohyoid laterally. The sternocleidomastoid is located lateral and superficial to the omohyoid. The very thin platysma muscle surrounds the neck, but its superficial location and indistinct density make it difficult to image with sonography. The thyroid gland appears as a rounded structure of low- to medium-level echoes, homogeneous in texture (Fig. 17-5B).

When imaged in the longitudinal (parasagittal) planes, the jugular vein and carotid artery appear as long, tubular, anechoic structures located laterally to the thyroid gland. Moving medially from these landmarks, the longus colli muscle, located posteriorly, becomes visible as a low-level, echogenic structure (Fig. 17-5C, D). The thyroid gland again is distinguished by its low- to medium-level, homogeneous echo pattern.

Thyroid cysts are common in humans but the term is often used loosely to define thyroid disease.¹⁸ The true epithelium-lined cysts in the region of the thyroid gland
are uncommon and are almost always benign.¹³ Two true cysts are the thyroglossal duct cyst and the branchial cleft cyst, which can be differentiated from each other by their location. Thyroglossal duct cysts tend to be midline and branchial cleft cysts tend to be lateral to the carotids. More information regarding these two cysts in presented in the section on Developmental Cysts.

Benign nodular thyroid disease is common among adults and the prevalence increases with age.¹⁹ Sonographic evaluation indicates that 15% to 25% of these solitary thyroid nodules are either cystic or predominantly cystic and are sonographically described as either a mixed or a complex lesion.^18,19 The etiology of the cystic portion of the thyroid nodule is usually hemorrhage or is subsequent degeneration of preexisting nodules.²⁰ FNA cytology provides the diagnosis of benign versus malignant and cystic versus solid lesions.¹⁸ Percutaneous ethanol injection is used to initially treat benign cystic nodules or as follow-up treatment for recurrent thyroid cysts.^19,20 The response rate to the ethanol injection ranges from 72.1% to 93.9%.¹⁸ Malignant cystic nodules are surgically removed.¹⁸

Sonographically, a simple cyst will be circular or oval, with discrete margins; contain no internal echoes; and exhibit posterior enhancement (Fig. 17-6A). Comet tail artifacts can frequently be encountered in complex cystic thyroid nodules, and they are likely related to the presence of colloid substances in the cyst²¹ (Fig. 17-6B). A hemorrhagic cyst may contain blood and debris and may appear as a complex mass with irregular borders and internal septa (Fig. 17-6C). When more densely echogenic fluid is gravitationally layered in the posterior portion of a cystic cavity, the likelihood of hemorrhagic debris is very high (Fig. 17-6D). Sonographically, papillary carcinomas may present with varying amounts of cystic change, may appear almost indistinguishable from benign cystic nodules, or may appear as uneven cystic structures, with finger-like pedunculated mass(es) larger than 2 cm seen projecting into the lumen¹⁸ (Fig. 17-6E). FNA is important to distinguish these from one another and to obtain a diagnosis.

In the United States, the estimated prevalence of thyroid nodules found by palpation alone ranges from 4% to 7% and sonography detects nodules in 20% to 76% of the adult population.²² They are more common in women and increase in frequency with age and with decreasing iodine intake.²² Based on the technetium-99m (Tc-99m) radioiodine scintigraphy examination, they are classified either as “hot” (hyperfunctioning/autonomous) or as “cold” (nonfunctioning).²³ A cold nodule is one that does not absorb the radiopharmaceutical used for evaluating the gland and therefore appears as an area of decreased or absent activity on the resulting nuclear image. In contrast, a hot nodule traps an excessive amount of isotope and presents as a dense collection of activity.

Patients with a thyroid nodule palpated on physical examination, which subsequently appear as cold nodules on a nuclear medicine study, are often referred to sonography for further evaluation. Approximately 80% to 85% of thyroid nodules are cold and 10% to 15% of these are malignant.²⁴ About 5% to 10% of solitary thyroid nodules are hot nodules, which usually implies benignity.²³ Currently, no single sonographic criterion distinguishes benign thyroid nodules from malignant thyroid nodules with complete reliability.¹⁰ It is possible to make an accurate prediction of malignancy and recommend FNA when suspicious sonographic signs are seen in combination with multiple signs of thyroid malignancy.

A thyroid adenoma is a benign, neoplastic growth of thyroid glandular epithelium usually contained within a fibrous capsule.⁶ Most adenomas are solitary but they may also develop as part of a multinodular process.¹⁰ Although the terms adenoma and nodule are used interchangeably, an adenoma is a specific new tissue growth (neoplastic) and a nodule may include a carcinoma, a normal gland lobule, or any other focal lesion. Benign adenomas account for 5% to 10% of thyroid nodules and are seven times more common in females than in males.¹⁰ Most adenomas are derived from follicular epithelium, and a small minority of these are toxic and cause hyperthyroidism owing to autonomous function.¹³ Based on the degree of follicle formation and the colloid content of the follicles, the rare adenomas make up these histologic subtype classifications: macrofollicular (simple colloid), microfollicular (fetal), embryonal (trabecular), Hürthle cell (oxyphil, oncocytic) adenomas, atypical adenomas, and adenomas with papillae.⁸ Adenomas grow slowly, remain dormant for years, and are more common in the fifth and sixth decades of life.⁶ In order to be palpated on physical examination, an adenoma must reach a size of 0.5 to 1 cm. This explains why sonography has detected small nodules on a thyroid gland that was not detected on palpation. When a hyperfunctioning adenoma suppresses normal thyroid gland tissue, the normal tissue atrophies and the adenoma appears as a hot nodule against a background of minimal uptake on a radionuclide examination.⁶ A toxic hyperfunctioning adenoma may provoke thyrotoxicosis. The distinction between toxic and nontoxic adenomas cannot be made with sonography. Adenomas are typically asymptomatic but can grow large enough to exert pressure or develop hemorrhage, thus, becoming problematic.

The sonographic features of adenomas are influenced by the amount of structural degeneration and vary widely, appearing cystic to complex or solid. One other sonographic feature previously thought to indicate a benign nodule often associated with an adenoma is calcification along the rim, but malignant nodules may also have this appearance¹⁰ (Fig. 17-7A, B). The most common appearance is that of a solitary, well-circumscribed, oval or circular mass of variable size and echogenicity. Small, solid adenomas with uniformly low echogenicity can be mistaken for cysts. The distinction is made by noting the absence of through sound transmission behind a solid lesion. A peripheral hypoechoic-to-anechoic halo that completely or incompletely surrounds an adenoma is a relatively consistent finding. The halo, however, cannot be used as the only criterion and additional statistical information is necessary to establish the halo’s specificity.⁹ A halo in the nodule periphery may be seen with benign or malignant conditions and suggests that there is an acoustic interface that does not reflect the ultrasound across two different types of histology in the region of the benign or malignant nodule and the surrounding thyroid gland.²⁵ In the case of an adenoma, this halo is thought to represent the fibrous capsule and the perinodal blood vessels, which can be seen by color Doppler imaging, and mild edema
or compressed normal thyroid parenchyma (Fig. 17-7C). Color Doppler imaging performed on an adenoma may have a “spoke and wheel” appearance with peripheral blood vessels extending toward the center of the lesion¹⁰ (Fig. 17-7D, E). Adenomas greater than 2.5 to 3 cm commonly display the sonographic characteristics of a complex cyst. These adenomatous cysts tend to have irregular shapes and borders with thickened walls, an incomplete capsule and are less sharply demarcated from surrounding tissue. Although imaging research is providing increased statistical probabilities to distinguish benign and malignant nodules, imaging procedures cannot be used as the only dependable criteria to distinguish adenomas from other benign or malignant nodules²¹ (Fig. 17-7F-I).

A nontoxic goiter is also termed simple, colloid, or multinodular and refers to an enlargement involving the entire gland without producing nodularity and without evidence of a functional disturbance.⁶ The enlarged follicles are filled with colloid.⁸ Nontoxic goiter occurs in both an endemic distribution with more than 10% of the population affected and a sporadic distribution.⁸ Endemic goiter occurs in geographic areas where the soil, water, and food supply contain low levels of iodine. The decrease or lack of iodine leads to decreased synthesis of thyroid hormone and a compensatory increase in TSH. Increased TSH levels lead to follicular cell hypertrophy, hyperplasia, and goitrous enlargement.⁸ Sporadic goiter is defined as a benign enlargement of the thyroid gland in euthyroid subjects living in an iodine-sufficient area. The sporadic goiter can be diffuse, uninodular, or multinodular.²⁶ The cause of sporadic goiter is usually not apparent and may be related to ingestion of substances or hereditary enzymatic defects that interfere with thyroid hormone synthesis.⁸ The peak age of subjects with sporadic goiter is between 35 and 60 years and women are three times more likely than men to have the disease.¹⁰

Owing to recurrent episodes of hyperplasia and involution, simple goiters may convert into multinodular goiters. Nodularity of the thyroid gland can be the end stage of diffuse nontoxic goiter. As new follicles develop and outgrow their blood supply, hemorrhagic necrosis of all or part of the nodule results. Scarring then produces an inelastic network into which new follicles are squeezed, resulting in the formation of nodules.¹⁴ Calcifications, fibrosis, degenerative cysts, and hemorrhage result in the heterogeneous sonographic appearance. Multinodular goiters may be multilobulated with an asymmetrically enlarged gland. The pattern and location of enlargement are unpredictable and may involve only one lobe or may expand growing behind the sternum and clavicles to produce the intrathoracic or plunging goiters.⁸ Multinodular goiters may be nontoxic or may induce thyrotoxicosis (toxic multinodular goiters). As is the case of the simple goiter, the incidence of multinodular goiter is greater in females than in males.

The size of nontoxic goiters ranges from a doubling in size (40 g) to a massive enlargement in which the thyroid weighs a few hundred grams to more than 2,000 g.^6,8 Symptoms caused by large goiters are usually associated with compressing the esophagus (dysphasia), trachea (inspiratory stridor), neck veins (venous congestion), or laryngeal nerve (hoarseness).⁶

The sonographic appearance may be nonspecific and varies with pathogenesis of the goiter. The visualization of a dominant nodule, a tender spot, or a region of focal hardness may provide pathologic clues²⁵ (Fig. 17-8A, B). A second type of pathology may be suggested if one region in a goiter presents an echo pattern distinct from the rest of the goiter. It is important to note if there is a region within the goiter that displays sonographic features associated with increased risk

for malignancy, which include hypoechogenicity, solidity, microcalcification, irregular margin, and a taller-than-wide shape²⁷ (Fig. 17-8C-F). Neoplasm and lymphomas have been demonstrated in goiters.²⁵ Table 17-2 lists additional usefulness of sonographic examinations in goitrous patients.

Thyrotoxicosis is a hypermetabolic state caused by elevated levels of free T₃ and T₄.²⁸ The terms thyrotoxicosis and hyperthyroidism are often used interchangeably because the condition is caused most commonly by hyperfunction of the thyroid gland.⁸ Hyperthyroidism is correct to use if elevated levels arise from hyperfunction, as occurs in Graves disease; thyrotoxicosis is correct to use if the increased hormone levels reflect excessive leakage of hormone out of a nonhyperactive gland.⁸ Primary hyperthyroidism is a form of thyrotoxicosis in which excess thyroid hormone is synthesized and secreted by the thyroid glands.⁸ Secondary hyperthyroidism is rare and is caused by TSH-secreting pituitary adenomas²⁸ (Pathology Box 17-1).

Pathogenesis of either thyrotoxicosis or hyperthyroidism produces common clinical manifestations (Pathology Box 17-2). Children with Graves disease often have accelerated growth spurts and advanced bone age, symptoms of emotional lability, hyperactivity, difficulty concentrating, and occasionally failure to thrive.

The underlying cause of hyperthyroidism in 50% to 80% of cases is Graves disease.²⁸ Graves disease is an autoimmune disease and about 75% of autoimmune diseases occur in women, most often during the childbearing years.²⁹ Graves disease can occur at any age or gender but is most common in women of reproductive age.³⁰ Research indicates a multifactorial etiology where different factors come together to cause Graves disease, such as heredity, the body’s immune system, age, gender, and possibly stress.²⁹

Graves disease is characterized as a multisystem syndrome consisting of one or more of the following: (1) hyperthyroidism, (2) diffuse thyroid enlargement (goiter), (3) ophthalmopathy (protrusion of the globe owing to fat accumulation and inflammation with edema), and (4) Graves dermopathy (pretibial myxedema characterized by subcutaneous swelling on the anterior portions of the legs and by indurated and erythematous skin).²⁸

Thyrotoxicosis has a variety of causes, and determining the cause is important because treatment and expected outcomes will vary accordingly, though it will normally focus on controlling excessive thyroid hormone production.²⁸ The diagnosis is based on symptoms of thyroid hormone excess and evaluating elevated serum-free T₄ and T₃ variances. TSH levels are increased in primary hyperthyroidism and decreased in secondary hyperthyroidism. Radioactive iodine uptake is a good diagnostic tool to determine the etiology of thyrotoxicosis.

Sonography for thyrotoxicosis and hyperthyroidism can assess the size of the thyroid gland to facilitate decisions regarding treatment.²⁵ Graves disease can present with either a normal-sized or an enlarged gland. When the gland is enlarged, the echo texture will usually be more heterogeneous compared to a diffuse goiter, which has numerous, large intraparenchymal vessels.¹⁰ Normal-sized glands will have a more uniform pattern. Hypervascularity is observed in most patients with Graves disease and has been quantified by the number of vessels per square centimeter measured on the greatest longitudinal view.³¹ The term “thyroid inferno” demonstrating multiple tiny areas of flow in the glandular tissue is often used to describe the hypervascular pattern
seen on color Doppler images (Fig. 17-9A-E). A bruit or thrill can often be heard over the gland. Spectral Doppler images may demonstrate peak velocities exceeding 70 cm/sec.¹⁰

Hypothyroidism is the most commonly occurring thyroid function disorder and affects between 0.1% and 2% of individuals in the United States.²⁸ It is a clinical syndrome caused by a deficient production of thyroid hormone that results in reduced thyroid hormone action in the peripheral tissues. Hypothyroidism may be primary or secondary. There is a greater incidence and increased number of causes of primary hypothyroidism arising from an intrinsic abnormality in the thyroid gland (Pathology Box 17-3). Secondary (central) hypothyroidism occurs less frequently than primary hypothyroidism and includes those conditions that cause either pituitary or hypothalamic disease or damage resulting in failure to stimulate normal thyroid function.²⁸ The conditions contributing to secondary hypothyroidism include pituitary adenoma; tumors impinging on the hypothalamus; irradiation; medication (dopamine, lithium); congenital disorders; and, rarely, Sheehan syndrome.