Thyroid Development

Thyroid development begins during the third week of gestation as a midline focus of endodermal thickening on the floor of the primitive pharynx. This thyroid diverticulum “descends” as the head and neck of the embryo grow, and reaches its normal location in the inferior aspect of the neck by approximately 7 weeks. The thyroid diverticulum becomes solid and divides into right and left lobes, with a connecting isthmus. The developing thyroid gland temporarily connects via the thyroglossal duct to its embryonic site of origin at the base of the tongue, the foramen cecum. The thyroglossal duct degenerates, and the foramen cecum persists as a small blind pit.

The most common developmental abnormalities of the thyroid gland involve failure of appropriate embryonic thyroid descent. Thyroglossal duct cyst is a remnant of the thyroglossal duct. An ectopic thyroid gland is due to failure of embryonic dissent. Accessory thyroid tissue can occur at any site along the embryonic descent pathway from the base of the tongue to the thyroid gland isthmus. In approximately 40% of children, there is a persistent inferior segment of the thyroglossal duct. This pyramidal lobe is a midline superior extension of the isthmus that can attach to the hyoid bone by fibrous or muscular tissue.

The normal thyroid gland is in the infrahyoid compartment of the neck. The right and left lobes are located lateral to the trachea, and there is an anterior connecting isthmus. Structures adjacent peripheral to the thyroid gland include the esophagus, carotid arteries, jugular veins, strap muscles, and longus coli muscles. The normal newborn thyroid gland is 1.8 to 2.0 cm long and the anteroposterior diameter is 0.8 to 0.9 cm. At 1 year of age, the mean length is 2.5 cm and the diameter is 1.2 to 1.5 cm. The length in adults is 4 to 6 cm and the diameter is 1.3 to 1.8 cm.

The normal thyroid parenchyma is homogeneous on diagnostic imaging studies. The iodine content results in a slightly hyperattenuating character on unenhanced CT images. Thyroid tissue is slightly hyperechoic relative to neck muscles on sonography. The thin hyperechoic capsule is often visible on high-resolution images. Colloid follicles are occasionally visible in the normal thyroid gland as 1 or more small cystic areas, less than 3 mm in diameter. Inspissated colloid sometimes results in an echogenic focus within the cyst (Figure 32-1).

Thyroid Scintigraphy

Of the available iodine isotopes, iodine-123 (¹²³I) is optimal for standard functional and scintigraphic examination of thyroid. ¹²³I has a short half-life and no β-emission; therefore, the thyroid radiation dose is relatively low. ¹²³I also has a γ emission energy that is ideal for scintigraphy. ^99mTc pertechnetate also well suited for thyroid imaging. This agent avidly accumulates in thyroid tissue, thereby providing the best anatomic detail of any of the thyroid scintigraphic agents. Because thyroid radiation exposure is much lower with this radiopharmaceutical than with an equal dose of radioiodine, a much higher dose can be administered and the image quality is thereby higher. Iodine-131 is utilized for treating hyperthyroidism and thyroid carcinoma, and is also used for thyroid carcinoma scintigraphy. Thallium-201 has utility in evaluating thyroid carcinoma. ^99mTc-methoxyisobutylisonitrile (MIBI) accumulates in many thyroid carcinomas.¹

For Iodine-123 imaging of the thyroid gland, the patient ingests the radiopharmaceutical in capsule form. Images are usually obtained at 2 and 4 hours. Iodine metabolism in the thyroid gland can be measured with the radioactive iodine uptake test, which is performed concomitantly with the standard imaging. A probe is utilized to measure thyroid gland activity 4 and 24 hours after oral administration of the capsule. In North America, normal radioiodine uptake values are 5% to 15% at 4 hours and 10% to 40% at 24 hours.

Morphological and functional assessment of the thyroid is also possible with ^99mTc-pertechnetate imaging. Images are obtained during a time window of 10 to 30 minutes after intravenous injection of the radiopharmaceutical. For functional assessment, thyroid gland counts are obtained with γ camera imaging at 2, 10, and 15 minutes after injection; comparative soft tissue activity is measured by obtaining counts of the thigh at 16 minutes. Uptake ratios are calculated as follows: 10-minute thyroid:2-minute thyroid, and 15-minute thyroid:16-minute thigh. Criteria for interpretation of the uptake ratios are reported in Table 32-1.

Clinical Presentations: Neonatal Hypothyroidism

The estimated incidence of neonatal hypothyroidism (congenital hypothyroidism) in the United States is approximately 1 infant in every 3000 to 4000 livebirths per year.^2,3 Hypothyroidism is classified into primary, secondary, and tertiary types. The secondary form is due to deficiency of thyroid-stimulating hormone (TSH; thyrotropin) and the tertiary from is due to deficient thyrotropin-releasing hormone (TRH). Primary hypothyroidism accounts for approximately 95% of cases. The various underlying conditions include defective development of the thyroid, intrinsic deficiency in hormone synthesis by the thyroid, intrauterine exposure to goitrogens, maternal iodine deficiency, maternal antibodies to the thyroid, and maternal usage of antithyroid medications. Infants with Down syndrome are at an elevated risk for hypothyroidism.^4,5

Most newborns with congenital hypothyroidism do not exhibit overt clinical manifestations of the abnormality, and detection of the hypothyroidism is by way of routine neonatal screening. Screening tests measure either serum TSH (thyrotropin) or thyroid hormone levels. Potential clinical findings of hypothyroidism (most often identified in older infants or young children with untreated disease) include abnormal facies, macroglossia, umbilical hernia, feeding problems, lethargy, dry skin, jaundice, subnormal temperature, constipation, respiratory abnormalities, and enlargement of the posterior fontanelle. Affected children suffer retarded skeletal maturation. Children with primary hypothyroidism have elevation of TSH levels and depressed thyroxine levels. Diminished blood TSH despite subnormal thyroid hormone levels indicates a diagnosis of secondary or tertiary hypothyroidism.

The most common cause of neonatal hypothyroidism is defective development of the thyroid gland; this is termed thyroid dysgenesis. Thyroid dysgenesis accounts for approximately 80% of instances of neonatal hypothyroidism. There are 3 main types of thyroid dysgenesis. Ectopic thyroid accounts for about three-quarters of cases of thyroid dysgenesis, athyreosis (complete absence of thyroid gland development) accounts for about one-quarter, and hypoplasia of the thyroid is rare. Intrinsic deficiency in hormone synthesis, termed dyshormonogenesis, accounts for 10% to 15% of cases of neonatal hypothyroidism. Occasionally, hypothyroidism is due to defective synthesis of TSH. There are rare examples of hypothyroidism caused by mutations that affect function of the receptor for TSH.

Systematic screening for congenital hypothyroidism in the neonate is mandatory in the United States and many other countries. Substantial neonatal hypothyroidism results in brain damage if not properly detected and treated during the first days of life. The initiation of early therapy with appropriate doses of thyroxine prevents brain damage even in infants with complete absence of the thyroid during fetal development (i.e., athyreosis) because transplacental passage of maternal thyroxine is protective.²

Scintigraphy is indicated for many children with neonatal hypothyroidism to define thyroid gland morphology. There are 4 scintigraphic patterns in hypothyroid infants: (1) normal gland, (2) no detectable thyroid activity, (3) normal gland location with or without enlargement, and (4) ectopic gland (Table 32-2). Approximately 45% of infants with hypothyroidism have an ectopic gland, athyreosis is demonstrated in 35%, 10% have a normal gland anatomically, and 10% have other abnormalities. The scintigraphic documentation of an ectopic gland or athyreosis mandates lifelong thyroid hormone replacement therapy. If scintigraphy shows a normally located gland and the diagnosis of transient hypothyroidism is considered possible, a trial of discontinuation of thyroid hormone replacement is usually indicated sometime after the second year of life. Infants with transient primary hypothyroidism have normal scintigraphy or weak uptake in a normally located gland.³

Sonography can be used to evaluate the thyroid in patients with congenital hypothyroidism, but is not the optimal primary imaging technique because of its poor sensitivity for the detection of ectopic thyroid. With athyrosis, no thyroid tissue is visible. Ectopic thyroid also results in a lack of a thyroid gland in the expected location at the base of the neck. The correct diagnosis is suggested when 1 or more homogeneous foci of ectopic tissue are demonstrated more superiorly in the neck, typically at the midline. Color Doppler imaging increases the sensitivity of ultrasound for the detection of ectopic tissue. Thyroid sonography in infants with dyshormonogenesis shows a normal-size or enlarged gland in a normal location.^6–8

Dysgenesis

The most common cause of neonatal hypothyroidism is dysgenesis, that is, a defect in the organogenesis of the gland. Thyroid dysgenesis consists of hypoplasia, ectopia, or absence of the gland. This anomaly occurs in approximately 1:3000 births. Mutations in the PAX-8 gene have been identified in some patients with thyroid dysgenesis. Other genes involved in thyroid gland embryogenesis include TTF-1 and TTF-2. Hypoplasia can result from TSH receptor mutations.^9–11

Thyroid dysgenesis is more prevalent in females, with a female-to-male ratio of approximately 2:1. Thyroid dysgenesis is more common among Hispanics than whites and is less prevalent in black infants. The prevalence is increased in infants with Down syndrome.

Athyreosis

Complete absence of thyroid gland development, termed athyreosis (athyrosis), accounts for about one-quarter of cases of thyroid dysgenesis. These children are profoundly hypothyroid. Prompt initiation of thyroid hormone replacement therapy is essential to minimize long-term morbidity. Laboratory examination shows elevated TSH and very low levels of T₃ and T₄. A lack of measurable plasma thyroglobulin supports the diagnosis of athyreosis.

The diagnosis of athyrosis is best established with scintigraphy, which shows no thyroid activity (Figure 32-2). The imaging field of view must extend from the base of the tongue to the upper mediastinum, to rule out an ectopic gland. Activity sometimes appears prominent in the salivary and lacrimal glands in patients with athyrosis because of the absent thyroid uptake.

Sonography can also be utilized to confirm a diagnosis of athyrosis; no thyroid tissue is visible. The examination must include a careful search for ectopic thyroid tissue. Patients with absence of a normal thyroid gland, either due to athyrosis or ectopic thyroid, sometimes have 1 or more cysts in the empty thyroid bed; these may represent thyroglossal duct cysts. The cysts may be solitary or, more commonly, multiple, and tend to be near the midline.¹²

Ectopic Thyroid

Ectopic thyroid is a form of thyroid dysgenesis in which there is thyroid tissue at a site other than the usual pretracheal location at the base of the neck. As the thyroid gland develops, it migrates along a path from the foramen caecum at the base of the tongue to its normal location in the lower neck. Arrested migration can result in an ectopic thyroid gland location anywhere along this path.¹³ An ectopic gland at the base of the tongue is termed a lingual thyroid; this is the most common type, and is the only thyroid in approximately 70% of patients with ectopic thyroid. Rarely, more than 1 ectopic rest occurs: the double ectopic thyroid.¹⁴ Ectopic thyroid is the most common cause of congenital hypothyroidism, accounting for approximately two-thirds of cases. Ectopic thyroid is more common in females.

Although some patients with ectopic thyroid are clinically and biochemically euthyroid, the volume of ectopic thyroid tissue often is insufficient to maintain normal thyroid hormone levels. Because the hypothyroidism in these patients is usually mild and the mass produced by the ectopic gland is small, the clinical presentation may be delayed until adolescence or adulthood. The child may present with an otherwise asymptomatic neck mass, or complain of dysphagia, a “lump in the throat” sensation, dyspnea, or dysphonia. Considerations in the differential diagnosis of a mass at the typical locations of an ectopic thyroid are noted in Table 32-3. Occasionally, a newborn thyroid function screen will detect hypothyroidism due to ectopic thyroid. Although small, the ectopic thyroid is usually otherwise normal. However, the clinical and imaging findings may be complicated by pathology within the ectopic gland, such as colloid cyst or autoimmune thyroiditis.^15,16

The optimal imaging technique for the diagnosis of ectopic thyroid is scintigraphy with ^99mTc-pertechnetate or iodine-123. Typically, there is no normal thyroid tissue in the expected location of the gland, and 1 or more foci are located ectopically along the course of the thyroglossal duct, that is, the midline of the upper portion of the neck (Figure 32-3). The ectopic tissue is most often located in the lingual, sublingual, or prelaryngeal areas. The imaging field of view must extend from the base of the tongue to the upper mediastinum to include all potential sites of ectopic thyroid tissue. A lateral view is helpful to document a lingual thyroid (Figure 32-4).

Sonography of neonates with hypothyroidism due to ectopic thyroid shows absence of normal thyroid tissue in the expected location at the base of the neck. In neonates, the ectopic focus may be demonstrated as a homogeneous hyperechoic mass along the embryonic pathway of the thyroglossal duct. The mass is hypervascular. A lingual thyroid is located at the base of the tongue adjacent to the hyoid bone. Sonography does not provide sufficient sensitivity for the diagnosis of the ectopic thyroid to be of use as a primary screening method. In older patients who have been treated with exogenous thyroid hormone, residual ectopic thyroid tissue often becomes hypoechoic and exhibits diminished vascularity.^17,18

Although the diagnosis of ectopic thyroid is best established with scintigraphy, this lesion is sometimes identified on CT or MR studies performed for patients with nonspecific or unrelated symptoms. The mass is homogeneous and the margins are well defined. The ectopic thyroid tissue usually has similar or identical imaging characteristics as normal thyroid tissue on CT and MR. Prominent homogeneous contrast enhancement of the ectopic thyroid tissue aids in the differentiation from adjacent normal soft tissues (Figure 32-5). On MR, ectopic thyroid tissue typically is isointense or mildly hyperintense relative to normal adjacent muscles on T1-weighted images. On T2-weighted images, the signal intensity is low to intermediate. The imaging appearance of a lingual thyroid is that of a well-defined round mass at the base of the tongue (Figure 32-6).^18,19

An accurate diagnosis of ectopic thyroid is essential for proper patient management. Thyroid hormone replacement therapy controls the size of the gland, and is sufficient treatment for most patients. ¹³¹I therapy is an option for patients with a large ectopic gland that does not respond sufficiently to L-thyroxine administration. Surgical removal is usually unwarranted; resection sometimes is performed in these patients because of a mistaken diagnosis of a neck neoplasm.

Thyroid Hypoplasia

Thyroid hypoplasia is usually sporadic, although familial occurrences have occasionally been described. Specific genetic defects have been implicated in only a small number of patients with thyroid hypoplasia. Loss-of-function mutations have been identified in PAX-8, which encodes a transcription factor involved in thyroid development. Autosomal recessive mutations of the TSH receptor gene have also been identified.^9,20 The severity of hypothyroidism varies between patients. Imaging of thyroid hypoplasia with scintigraphy or cross-sectional imaging shows a small gland that otherwise appears normal.

Hemiagenesis

Hemiagenesis refers to lack of development of 1 lobe of the thyroid. The estimated prevalence is 1:1900 to 1:2675 births. Hemiagenesis is slightly more common in females. Absence of the left lobe is more common, with a left-to-right ratio of 3.6:1. This disorder is familial in some patients. Most individuals with hemiagenesis are euthyroid. Iodine or pertechnetate scintigraphy demonstrates a solitary right or left lobe (Figure 32-7). The appearance of hemiagenesis occasionally leads to a mistaken diagnosis of a solitary hyperfunctioning nodule with scintigraphy. The correct diagnosis can be established by correlation with cross-sectional imaging, such as sonography (Figure 32-8).^21,22

Dyshormonogenesis

Dyshormonogenesis refers to genetic enzymatic abnormalities in the biochemical pathway of thyroid hormone formation. Any of the metabolic steps in thyroid hormone synthesis can be involved. Dyshormonogenesis most often has an autosomal recessive pattern of inheritance. Dyshormonogenesis accounts for 10% to 15% of cases of neonatal hypothyroidism.²³

Thyroid hormone synthesis is regulated by TSH, which is secreted by the pituitary gland. The TSH binds to a receptor in the plasma membrane of the thyroid cell. Iodide is taken up in the thyroid gland by an active process (sodium iodide symporter) that is also located in the plasma membrane. Iodide transport results in an intrathyroidal iodine concentration of between 10 and 100 times the plasma concentration. Iodide is then oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin. Thyroglobulin is a matrix protein in which iodotyrosines are coupled to form thyroid hormone (T3 and T4). Thyroid peroxidase serves to catalyze both iodination and coupling. Thyroglobulin that contains thyroid hormone is stored in the follicular lumen until release is called for. Release of thyroid hormone from thyroglobulin is achieved by endocytosis and phagolysosomal proteolysis.²³

The most common inborn errors in thyroid hormone synthesis are related to iodide organification defects. These can result from abnormalities in thyroid peroxidase or in the H₂O₂ generating system. The thyroid peroxidase gene is located on chromosome 2p25. A partial organification defect occurs in children with Pendred syndrome (hypothyroidism, goiter, sensorineural hearing impairment). Patients with genetic defects that compromise iodide transport suffer hypothyroidism that may vary in severity with the dietary iodine intake.

Genetic defects in thyroglobulin synthesis are rare, with an incidence of approximately 1 in 100,000 newborns. Most are inherited as autosomal recessive traits. The plasma thyroglobulin level is usually low in these patients. Effective formation of thyroid hormone cannot occur when the structure of thyroglobulin is abnormal, despite TSH stimulation that causes increase in thyroglobulin synthesis, iodide uptake, oxidation, and organification.

Scintigraphy with pertechnetate or radioiodine in patients with dyshormonogenesis typically shows an enlarged thyroid gland in a normal location (Figure 32-9). The elevated TSH levels stimulate the trapping mechanism, resulting in intense accumulation of radiopharmaceutical within the thyroid and diminished general soft tissue activity. The appearance is often similar to that of Graves disease, except the blood thyroid hormone levels are low (Table 32-4). Because organification defects are common in children with dyshormonogenesis, scintigraphy with iodine may show normal trapping, but rapid elimination of the unorganified iodide after administration of perchlorate, that is, a positive perchlorate washout test. The thyroid gland takes up the perchlorate ion in a similar manner as iodine; there is displacement of some of the iodine that is not bound by way of organification. A decrease of at least 10% to 15% in thyroid ¹²³I after the oral administration of potassium perchlorate is considered a positive result for the perchlorate washout test.²⁴

Secondary and Tertiary Hypothyroidism

Secondary hypothyroidism results from deficiency of TSH, whereas tertiary hypothyroidism refers to deficiency of TRH. Idiopathic pituitary aplasia or congenital midline brain defects such as septooptic dysplasia, holoprosencephaly, and cleft palate are associated with these forms of hypothyroidism. Autosomal recessive gene defects, including Pit-1 and PROP-1, have been implicated in some patients. The secondary and tertiary forms of hypothyroidism account for less than 5% of cases of neonatal hypothyroidism.

The diagnosis of secondary or tertiary hypothyroidism is suggested when the serum level of TSH is normal or low despite subnormal blood thyroid hormone levels. Deficient secretion of TSH by the pituitary gland is suggested if an appropriate elevation of TSH does not occur in response to administration of TRH. Secondary hypothyroidism due to TSH deficiency can occur as an isolated endocrinopathy or in association with other pituitary hormone deficiencies. Deficient secretion of TRH by the hypothalamus is inferred if serum TSH levels normalize after administration of TRH. Scintigraphy is not clinically necessary for the evaluation of children with secondary or tertiary hypothyroidism. Because of the lack of TSH stimulation, radionuclide uptake is diminished to the point that the gland is typically not visualized with scintigraphy in these children.

Transient Neonatal Hypothyroidism

The concentration of thyroid hormone in fetal blood increases progressively with gestational age. All premature infants have some degree of thyroid hormone deficiency (transient hypothyroxinemia), likely due to hypothalamic immaturity. Typically, the TSH levels are normal or slightly diminished in these infants. Spontaneous normalization of thyroid hormone production occurs during the first 1 to 2 months of life, and treatment is not required unless substantial elevations in TSH levels occur.²⁵

Transient primary (neonatal) hypothyroidism refers to a self-limited form of hypothyroidism that is characterized by low serum thyroid hormone levels and elevated TSH levels. This most often occurs in premature infants, and the manifestations are superimposed on the expected transient thyroid hormone deficiency that is characteristic of prematurity. The condition usually develops during the first 1 to 2 weeks of life. Transient primary hypothyroidism affects approximately 0.2% of premature infants in North America, and is more frequent in very low birth weight premature infants. Transient primary hypothyroidism is more common in Europe than in North America.

Various mechanisms have been implicated for transient primary hypothyroidism in neonates. Maternal dietary iodine deficiency appears to be the most common cause. The prevalence of transient hypothyroidism in premature infants is elevated in geographic regions with low dietary iodine intake, and term infants can also be affected in these areas. Other potential mechanisms of transient hypothyroidism include iodine overload (the Wolff-Chaikoff effect), exposure to antithyroid medications, and placental transfer of TSH receptor blocking antibodies. Potential sources of iodine exposure in the neonate include iodine-containing skin antiseptics, iodine-containing medications, and radiological contrast agents.²⁶

Scintigraphy with pertechnetate or iodine-123 in infants with transient hypothyroidism usually shows normal thyroid gland morphology. Some infants with hypothyroidism due to iodine deficiency, iodine excess, or in utero exposure to antithyroid medications have an enlarged thyroid gland. The intensity of radiopharmaceutical uptake varies between patients, but is often diminished. The demonstration of an intact thyroid gland in the infant with suspected transient hypothyroidism effectively rules out athyreosis and ectopic thyroid; therefore, withdrawal of thyroid hormone replacement therapy can be attempted after an appropriate course of treatment.

Bacterial Thyroiditis

Acute bacterial (suppurative) thyroiditis is rare. Bacterial thyroiditis in children is often related to a pyriform sinus fistula or thyroglossal duct remnant, especially when infections are recurrent. Because of the association with pyriform sinus fistula, which is located on the left in greater than 90% of affected patients, bacterial thyroiditis most often occurs in the left lobe. Fever, neck pain, hoarseness, dysphagia, and neck swelling are the most common signs and symptoms. Thyroid function tests are usually normal.

Acute bacterial thyroiditis is usually caused by oropharyngeal flora. Streptococcal species are most common (approximately 50%); many of the infections involve mixed pathogens (anaerobes, staphylococci, and Eikenella corrodens).²⁷ Percutaneous aspiration of the abnormal portion of the thyroid gland is frequently helpful in patients with suspected suppurative thyroiditis to establish a bacteriological diagnosis. When there is an underlying pyriform sinus fistula, complete surgical removal of the fistula is required to prevent recurrence of thyroid infection.²⁸

Progression of bacterial thyroiditis to abscess formation is uncommon in children, particularly during the first decade of life. Although systemic symptoms are often lacking or mild with uncomplicated bacterial thyroiditis, an abscess is typically accompanied by overt systemic manifestations of illness such as fever and chills. The affected portion of the thyroid gland may be enlarged and firm on palpation.

Thyroid scintigraphy of suppurative thyroiditis shows heterogeneous decreased uptake in the involved portion of the thyroid. This is due to inflammation, edema, and diminished function of infected cells. Most frequently, the infection is confined to 1 lobe. Occasionally, 1 or more “cold” foci are present, due to necrosis or abscess formation.

Early in the course of acute bacterial thyroiditis, sonography usually demonstrates irregular enlargement of the involved portion of the gland, with diffuse hypoechogenicity. There frequently are scattered foci of increased and decreased echogenicity. An abscess is indicated by a localized hypoechoic fluid collection. The margins of an abscess are often somewhat irregular. Debris is usually visible within the cavity, and a fluid-debris level may be evident.²⁹

Patients with bacterial thyroiditis should undergo an esophagram with barium and/or water-soluble contrast material to detect a pyriform sinus fistula. The fistula appears as a thin tract that arises from the apex of the pyriform sinus. The subsequent course is variable: it may pass ventral to the thyroid or penetrate through the upper portion of the gland. The fistula can extend as far inferiorly as the clavicle. Edema during episodes of acute inflammation may interfere with passage of contrast into the fistula. Visualization of the fistula is facilitated by use of the “trumpet maneuver.” The fistula is occasionally demonstrable with sonography as a hypoechoic tract. Echogenic bubbles of air can be observed passing into the fistula during the trumpet maneuver.

Cross-sectional imaging with CT or MR delineates inflammation associated with a pyriform sinus fistula. These studies are also useful to detect a thyroid abscess. Inflammation of the thyroid causes decreased attenuation on CT and elevated signal on T2-weighted MR. An abscess is indicated by prominent contrast enhancement surrounding a nonenhancing focus. Occasionally, a pyriform sinus fistula leads to inflammation or abscess formation in the adjacent tissues rather than in the thyroid itself. Imaging with sonography, CT, or MR shows inflammatory changes in the parathyroidal tissues, typically on the left. The inflammatory abnormality may extend to the apex of the pyriform sinus.^30–32

Subacute Thyroiditis

Subacute thyroiditis is an inflammatory process of the thyroid that occurs in association with a viral infection. Subacute thyroiditis is often preceded by an upper respiratory tract illness. Commonly associated viruses include mumps, coxsackievirus, influenza virus, echovirus, and adenoviruses. The pathophysiology likely involves a post-viral inflammatory response that produces giant cell infiltration of the thyroid follicles. The follicles swell and eventually disrupt, with subsequent release of stored thyroid hormone into the blood. Swelling of the thyroid gland causes pain and tenderness to palpation. Thyroid hormone release results in clinical manifestations of thyrotoxicosis. Subacute thyroiditis is quite rare in young children, and most pediatric cases occur in teenagers. Other terms for subacute thyroiditis include subacute granulomatous thyroiditis, giant cell thyroiditis, and de Quervain thyroiditis.^33,34

The clinical presentation of subacute thyroiditis typically consists of either gradual or abrupt onset pain in the region of the thyroid gland; dysphagia and hoarseness can also occur. The clinical presentation sometimes mimics that of suppurative thyroiditis. Clinical manifestations of thyrotoxicosis develop in about half of patients during the acute phase, with palpitations and nervousness. Many patients experience a prodromal illness, with low-grade fever, sore throat, and myalgias. During the acute phase of the disease, the erythrocyte sedimentation rate is elevated, blood thyroid hormone levels are elevated, and TSH levels are suppressed. Subsequently, thyroid hormone levels fall to normal or subnormal ranges due to depletion of thyroid hormone stores, diminished TSH, and follicular cell destruction; this phase usually lasts for a few weeks. As blood thyroid hormone levels fall, TSH levels increase and sometimes become mildly elevated. In most patients, complete clinical recovery and normalization of laboratory values occur within 3 to 6 months of the clinical onset. Residual thyromegaly or mild hypothyroidism persists in approximately 10% of patients.^35–37

Scintigraphy with either iodine or pertechnetate typically demonstrates a patchy heterogeneous appearance of the thyroid in patients with subacute thyroiditis. This appearance is predominantly due to inflammation. Early in the course of the disease, there may be a relatively localized area of photopenia, with subsequent progression to the remainder of the gland. Localized inflammation can produce the scintigraphic pattern of a cold nodule. In some patients, subacute thyroiditis results in nonvisualization of the thyroid or only faint uptake. Thyroid inflammation interferes with transport and organification of iodine, and therefore the radioiodine uptake values are very low. Low TSH levels also result in diminished radionuclide uptake. During the healing phase of subacute thyroiditis, radionuclide uptake values may normalize or, if the TSH levels are increased, climb into the hyperthyroid range.^38,39

During the initial phase of subacute thyroiditis, sonography shows enlargement and diffuse or multifocal hypoechogenicity of the gland; this corresponds to inflammation and edema. Manifestations of hyperemia are lacking on Doppler evaluation. The sonographic abnormality may involve irregularly shaped focal regions, an entire lobe, or the entire gland. Compression of the thyroid with the transducer often elicits pain. Cervical lymphadenopathy is sometimes present. During the remission phase, the hypoechoic appearance usually disappears, and there may be a transient period of slightly increased vascularity that lasts for several months. Complete resolution of sonographic abnormalities eventually occurs in most children with subacute thyroiditis; a minority of patients has residual diffuse, focal, or multifocal hypoechoic lesions due to fibrosis.^40,41

The treatment of patients with subacute thyroiditis involves suppression of thyroid inflammation with medical therapy. Nonsteroidal anti-inflammatory medications are sufficient for many patients. Steroid therapy is sometimes required for severe cases.

Goiter is a nonspecific term that indicates enlargement of the thyroid gland, that is, thyromegaly. In general, enlargement of the thyroid can occur due to an increase in the number or size of otherwise normal thyroid cells (such as occurs with hyperstimulation) or due to an infiltrative process (Table 32-5). Examples of hyperstimulation include Graves disease and dyshormonogenesis. Infiltrative processes include infectious, inflammatory, and neoplastic conditions. Enlargement of the thyroid gland is sometimes related to abnormal dietary iodine intake; this can occur both with iodine deficiency (endemic goiter) and exposure to excess iodine (iodide goiter). Enlargement of the thyroid gland in neonates can occur in association with dyshormonogenesis, neonatal Graves disease, maternal ingestion of antithyroid medications or iodides, and transplacental passage of thyroid stimulating antibody (maternal Graves disease). Goiters in infants and young children are most often due to maternal ingestion of goitrogens or to an organification defect in thyroid hormone synthesis (dyshormonogenesis). In teenagers, Graves disease and thyroiditis are frequent causes of goiter.⁴²

Simple goiter (diffuse nontoxic goiter; colloid goiter) refers to diffuse enlargement of the thyroid gland due to excessive replication of epithelial cells and the generation of new follicles in a euthyroid patient who has no evidence of thyroid inflammation or neoplasm. The pathogenesis of simple goiter varies between patients, and is sometimes multifactorial. Potential mechanisms include stimulation by TSH (e.g., iodine shortage), extrathyroidal immunological growth factors, and local thyroidal tissue growth regulating factors. The thyroid gland in patients with simple goiter has a normal response to TSH. Physical examination shows mild-to-moderate thyromegaly. The gland is smooth, firm, and nontender. Simple goiter is more common in girls. Most affected pediatric patients are adolescents.⁴³

Simple goiter sometimes progresses to a multinodular form that is termed nontoxic multinodular goiter. This transition occurs by several mechanisms. Scarring and the accumulation of interstitial tissue form an inelastic network that isolates populations of growing follicles. Epithelial cell clones may replicate at different rates, with some clones forming nodules that consist of follicles histologically identical to those elsewhere in the thyroid. True adenomas can be present in nontoxic multinodular goiter, but are uncommon. Portions of the thyroid gland frequently develop some degree of functional autonomy in patients with nontoxic multinodular goiter (i.e., secretion of thyroid hormone despite absent TSH stimulation). Autonomous function may eventually involve enough of the gland to produce thyrotoxicosis; the condition is then termed toxic multinodular goiter.⁴⁴

Diagnostic imaging studies of patients with simple goiter show nonspecific thyromegaly. With sonography, the gland is relatively homogeneous. Mild heterogeneity may be present on scintigraphy with iodine-123 or ^99mTc-pertechnetate, due to regional variability of structure and function among the follicles. Although the findings on imaging studies do not allow a specific diagnosis of simple goiter, confident differentiation from multinodular goiter and neoplasm is usually possible.

The thyroid gland in patients with nontoxic multinodular goiter contains cystic areas, hemorrhage, and fibrosis, resulting in a heterogeneous echo pattern on sonography. Multiple cysts and hypoechoic nodules are usually present. CT and MRI also show a heterogeneous appearance. Cysts and foci of hemorrhage appear on CT as nonenhancing low attenuation areas; on MR, there are foci of high signal intensity on T2-weighted images. Clear cysts have low signal intensity on T1-weighted images, whereas subacute hemorrhage results in high signal intensity. Areas of adenomatous hyperplasia in these patients are hypointense or isointense to normal thyroid on T1-weighted images and hyperintense on T2-weighted images. In addition to demonstrating thyroid gland morphology, CT and MR provide excellent depiction of the effects of the enlarged gland on adjacent structures such as the airway.