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Chapter 526

The thyroid gland develops as an endodermal diverticular outpouching from the floor of the pharynx during the third week of gestation, at a site that persists as the foramen cecum at the base of the tongue in adults. The medial thyroid anlage descends in the neck anterior to structures that form the hyoid bone and larynx. During its descent, the anlage remains connected to the foramen cecum via an epithelial-lined tube known as the thyroglossal duct. The epithelial cells making up the anlage give rise to the thyroid follicular cells. Paired lateral anlages originate from the fourth branchial pouch and fuse with the median anlage at approximately the fifth week of gestation. The lateral anlages are neuroectodermal in origin (ultimobranchial bodies) and provide the calcitonin-producing parafollicular or C cells, which come to lie in the superoposterior region of the gland. Thyroid follicles are initially apparent by 8 weeks, and colloid formation begins by the 11th week of gestation. The growth and descent of the thyroid into the neck requires the coordinated action of multiple transcription factors. TTF-1, TTF-2, and PAX-8 are expressed just before and after the appearance of the thyroid diverticulum. Targeted disruption of the TTF-1 gene in mice results in complete absence of the thyroid gland, whereas disruption of PAX-8 results in a small thyroid that lacks follicles.

The thyroid forms bilateral lobes connected by an isthmus in the middle, typically just below the cricoid cartilage. In about 50% of individuals, there is a pyramidal lobe in the midline that represents the most caudal end of the thyroglossal duct. Persistence of the thyroglossal duct results in formation of a thyroglossal cyst. Lack of descent leads to a lingual thyroid.

### Metabolism of Dietary Iodine

The thyroid gland concentrates iodide from the blood and returns it to peripheral tissues in a hormonally active form. The major substrates for thyroid hormone synthesis are iodide and the amino acid tyrosine. Iodine is absorbed from the upper gastrointestinal tract, where it is distributed within the extrathyroidal iodide pool.1,2 The rate of thyroid iodide trapping is inversely related to the rate of renal iodide excretion. Iodide is excreted largely in urine through glomerular filtration; 1% to 2% may be excreted in sweat under basal conditions and as much as 10% with severe sweating. There is continuous secretion of iodide by the salivary and digestive glands, but this is reabsorbed; there is no substantial fecal excretion.

### Biosynthesis of Thyroid Hormone

Iodide is transported across the cell membrane into the thyroid follicular cell by a sodium-iodide symporter (NIS). The symporter normally generates a thyroid to a serum concentration gradient of 30- to 40-fold. This gradient can reach several hundredfold when the thyroid gland is stimulated by a low iodine diet, by thyroid-stimulating hormone (TSH), or by thyroid-stimulating immunoglobulins in Graves disease. The iodide traverses the cell from the plasma membrane to ...

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