Chapter 27: Disorders of the Thyroid Gland

NORMAL THYROID GLAND DEVELOPMENT AND FUNCTION

The thyroid gland is the first of the body’s endocrine glands to develop (~24th day of gestation), and its maturation can be divided into two phases. The first phase involves embryogenesis of the thyroid gland and of the hypothalamic-pituitary-thyroidal (HPT) axis. The second phase involves further development of the HPT axis, including hormone production and regulation.

Embryogenesis and Differentiation

The thyroid gland originates from the median anlage and from two lateral anlagen. The single median anlage gives rise to the vast majority of the thyroxine-producing follicular cells: it evolves from an outpouching of the floor of the pharynx at the base of the tongue that will remain visible as a depression, the foramen cecum (between the first and second branchial arches). As the thyroid gland develops, it descends through the tissues of the neck, remaining connected to the foramen cecum by the thyroglossal duct, which generally solidifies and subsequently becomes entirely obliterated (during gestational weeks 7–10). Failure of subsequent closure and obliteration of the thyroglossal duct predisposes to thyroglossal cyst formation. The two lateral anlagen (one on each side of the neck) derive from the fourth branchial pouches and they eventually fuse with the median anlage. The lateral anlagen are the main source of the calcitonin-secreting cells (parafollicular or C cells). Recent evidence has revealed calcitonin-producing cells in the median anlage as well,¹ challenging the long-held notion that they were exclusively of neural crest origin. The calcitonin-producing cells become dispersed between the thyroid follicles.

The thyroid follicular cells, which appear at week 9 to 10 of gestation, are the major cellular component of the thyroid. They are organized in a structure made of a single layer of polarized cells surrounding a colloid-containing lumen, the thyroid follicle.

Hormone Synthesis

From the functional standpoint, the thyroid can be envisioned as a structure that extracts and concentrates the iodine that reaches the gland through the bloodstream to convert it into thyroxine (T₄) and triiodothyronine (T₃) (Figure 27-1). Briefly, iodide is taken up at the basal membrane of the follicular cells through a sodium-iodine symporter (NIS) and is transported to the apical membrane, where thyroid hormone synthesis is initiated at the cell–colloid interface, involving iodide transporters (pendrin and possibly other proteins), a peroxidase (thyroid peroxidase [TPO]), and a peroxide-generating system that includes thyroid oxidases, DUOX1 and DUOX2 and their respective maturation factors DUOXA1 and DUOXA2;² peroxide (H₂O₂) generation is the limiting step in thyroid hormone biosynthesis. In addition to the oxidation of iodine, TPO catalyzes the iodination of selected tyrosine residues within thyroglobulin (a process called organification of iodine) resulting in the formation of mono- and diiodotyrosines. Mono- and diiodotyrosines assemble (a process called coupling, which is also catalyzed by TPO) to make T₄ and T₃. ...