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The Normal Thyroid Gland

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The Normal Thyroid Gland 1 THE NORMAL THYROID GLAND EMBRYOLOGY before lumen formation and colloid secretion The thyroid anlage appears as a bilobate ve- can be detected (4,5). sicular structure at the foramen cecum of the It has recently become clear that thyroid gland tongue. It then descends as a component of the organogenesis and the differentiation of follicular thyroglossal duct to reach its definitive position in cells are directed by the concerted action of a series the neck (fig. -). After involution of the thyro- of transcription factors, while thyroid-stimulating glossal duct, the thyroid anlage begins to expand hormone (TSH) influences thyroid differentiation laterally to form the thyroid lobes (–3). only after the anatomic outline of the gland is well Microscopically, the initially solid thyroid established. The most important of these tran- anlage begins to form cords and plates of fol- scription factors are thyroid transcription factor licular cells during the 9th gestational week. A (TTF)- (Nkx2-), TTF-2 (Foxe), PAX8, and Hhex small lumen appears within the follicles by the (6). Although these factors are also expressed and 0th week, with colloid secretion becoming influence differentiation in other developing tis- evident by the 2th week. By the 4th week, sues, all four are coexpressed only in the thyroid the gland already consists of well-developed anlage (6). Since they regulate the expression follicles lined by follicular cells and containing of thyroid-specific genes (e.g., those responsible thyroglobulin-positive colloid in their lumens for the production of thyroid peroxidase and (figs. -2–-3). Labeled amino acid studies have thyroglobulin) they are important not only for shown that thyroglobulin synthesis begins at a organogenesis but for the functional differen- very early stage, when the thyroid gland is still tiation of the gland in later stages of prenatal a solid mass at the base of the tongue, and long development and postnatally (6,7). Figure 1-1 BRANCHIAL ARCHES AND THEIR DERIVATES The branchial arches (A) and the adult organs that arise from them (B) are illustrated schematically. Note the thyroid anlage in the midline, attached to the thyroglossal duct. Tumors of the Thyroid and Parathyroid Glands Figure 1-2 Figure 1-3 FETAL THYROID GLAND FETAL THYROID GLAND A small lumen appears in the minute follicles of a 0- Well-developed small follicles have small lumens week fetal thyroid gland. that contain colloid in a 2-week fetal thyroid gland (thyroglobulin immunostain). Figure 1-4 FETAL THYROID GLAND Calcitonin is demonstrable immunohistochemically in the fetal thyroid gland. 2 The Normal Thyroid Gland Embryologic, histochemical, and immuno- along either side of the larynx to the midportion histochemical studies have led to the conclusion of the thyroid cartilage. Their upper and lower that the C-cells (the primary site of synthesis and extremities are referred to as the upper and lower storage of calcitonin) are derived from the neural poles of the gland, respectively. The two lobes crest and that they migrate to the ultimobran- are joined by the isthmus, which lies across the chial bodies before their incorporation into the trachea anteriorly, below the level of the cricoid thyroid gland (fig. -4) (8–2). The ultimobran- cartilage. Sometimes one lobe (particularly the chial bodies, in turn, are derived from branchial right) is larger than the other. In some individu- pouch complex IV-V (3). In some species, such als, the isthmus is unusually wide. as birds, the thyroid gland and the ultimobran- A pyramidal lobe is a vestige of the thyroglossal chial bodies are separate structures in the adult, duct and is found in about 40 percent of normal and the C-cells are confined to the latter. individuals. It is a narrow projection of thyroid The development of the ultimobranchial body tissue extending upward from the isthmus and is divisible into four stages: ) branchial pouch lying on the surface of the thyroid cartilage. stage (3 to 2 mm, 5 to 7 weeks); 2) separation Any diffuse pathologic process (such as diffuse stage (3 to 7 mm, 7 to 8 weeks); 3) incorpora- hyperplasia or Hashimoto thyroiditis) can result tion stage (8 to 27 mm, 8 to 9 weeks); and 4) in gross enlargement of the pyramidal lobe. dissolution stage (28 to 520 mm, 9 weeks to term) The normal weight of the thyroid gland in a (3). In the branchial pouch stage, the ultimobran- middle-aged adult is 5 to 25 g in areas without chial body is a thick-walled stratified epithelial endemic goiter. As an average, each lobe mea- cyst that is in continuity with the primitive pha- sures 4.0 x .5–2.0 x 2.0–4.0 cm, and the isthmus ryngeal cavity. At the beginning of the separation measures 2.0 x 2.0 x 0.2-0.6 cm. There are, how- stage, pouch complex IV-V separates into the ever, marked variations related to functional activ- parathyroid IV and the ultimobranchial compo- ity, gender, hormonal status, size of the individual, nent, the latter of which ultimately divides into and amount of iodine intake. The thyroid gland central and peripheral portions in the dissolu- is larger and heavier in women than in men, and tion phase. The central portion is represented it becomes even larger during pregnancy. by a stratified epithelial-lined cyst, whereas the The thyroid gland is completely enveloped peripheral portion is dispersed into a few cell by a continuous fibrous capsule, with septa that groups that eventually become cystic. divide the gland incompletely into lobules. The Additional support for the ultimobranchial parathyroid glands are usually located adjacent origin of the C-cells is provided by studies of to the posterior surface of the thyroid lobes (see patients with the DiGeorge syndrome (4,5). chapter 23). The recurrent laryngeal nerves run Affected individuals typically have complete or in the cleft between the trachea and esophagus, partial absence of derivatives of pouch complexes just medial to the thyroid lobes. III and IV-V. In studies reported by Burke et al. The thyroid blood supply derives from the (4), only 27 percent of patients with DiGeorge right and left superior thyroid arteries (which syndrome had C-cells within their thyroid gland. arise from the external carotid artery) and the In contrast, the number of bronchopulmonary right and left inferior thyroid arteries (which calcitonin-containing cells was within normal arise from the thyrocervical trunk of the sub- limits. These observations support the inter- clavian arteries). The thyroid veins drain into pretation that the bronchopulmonary calcito- the internal jugular, the brachycephalic, and, nin-containing cells develop independently of occasionally, the anterior jugular veins. derivatives of branchial pouches III and IV-V. The thyroid gland is endowed with a rich lymphatic network that encircles the follicles ANATOMY and connects both lobes through the isthmus. The normal adult thyroid gland is a bilobate In neonates and children, some of these lymph structure located in the midportion of the neck, vessels appear as empty, elongated, tortuous immediately in front of the larynx and trachea. spaces that simulate a retraction artifact but It wraps itself around these two structures and which are lined by D2-40–positive lymphatic firmly adheres to them. The two lobes extend endothelial cells (6). This network coalesces in 3 Tumors of the Thyroid and Parathyroid Glands Table 1-1 REGIONAL LYMPH NODES OF THE THYROID GLANDa The pericapsular nodes: whole organ sections of the thyroid have shown that the intraglandular lymph vessels penetrate the capsule and merge with the pericapsular lymph nodes forming a plexus around the gland (7) The internal jugular chain nodes (including the subdigastric nodes) The pretracheal, paratracheal, and prelaryngeal nodes: the pretracheal node located near the thyroid isthmus is sometimes referred to as the Delphian node The recurrent laryngeal nerve chain nodes The retropharyngeal and retroesophageal nodes aThe anterosuperior mediastinal nodes are secondary to the recurrent laryngeal nerve chain and pretracheal groups; however, studies have shown that dye injected into the thyroid isthmus can also drain directly into them (8). the subcapsular region to give rise to the median superior, median inferior, right and left lateral, and posterosuperior trunks. These collecting trunks leave the organ in close proximity to the veins to empty into the regional lymph nodes, which are shown in Table - and figure -5. Some correlation exists between the site of a thyroid carcinoma within the gland and the location of the initial lymph node metastasis. For instance, involvement of the subdigastric nodes of the internal jugular chain is common with upper pole lesions. However, the degree of anastomosis between these various nodal groups is such that any may be the site of disease regardless of the precise location of the primary tumor. Even the nodes of the posterior triangle group are affected with some frequency. Conversely, submandibular triangle involvement is rare and usually limited to cases with extensive metastases in other cervical nodal groups. Similarly, involvement of antero- superior mediastinal nodes is rarely seen in the absence of widespread cervical disease. HISTOLOGY The functional unit of the thyroid gland is the follicle, a closed sac lined by a single layer of epithelial glandular cells known as follicular Figure 1-5 cells. The average diameter of the follicle is 200 LYMPHATIC DRAINAGE OF THE THYROID GLAND nm, but there is considerable variation in size, depending on the degree of activity of the gland. This figure illustrates the medial superior trunk (), the median inferior trunk (2), the right and left lateral trunks The shape of the normal follicle varies from (3,4), and the posterosuperior trunks (5,6). All of these drain round to oval. Markedly elongated tubular and to the regional lymph nodes listed in the Table -.
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