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EMBRYOLOGY

The thyroid gland originates from a median anlage and paired lateral anlagen during the third week of gestation, at a site that persists as the foramen cecum at the base of the tongue in adults. The median anlage is derived from the primitive pharyngeal floor and the lateral anlagen from the fourth pharyngeal pouches. 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 lateral anlagen fuse with the median anlage at approximately the fifth week of gestation. It was previously believed that the median anlage is the source of origin of the follicular cells and the lateral anlagen is the source of calcitonin-producing parafollicular cells. This notion has been challenged by the demonstration of calcitonin-producing cells in ectopic lingual thyroid and the histologic observation of thyroid follicular cells differentiated within the lateral anlagen. Thyroid follicles are initially apparent by 8 weeks, and colloid formation begins by the 11th week of gestation. 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.

The growth and descent of the thyroid into the neck requires the coordinated action of multiple transcription factors. The simultaneous expression of the thyroid transcription factors NKX2-1 (formerly TTF-1), FOXE1 (formerly TTF-2), PAX8, and HHEX is essential for the proper development of the thyroid gland and for maintaining the functional differentiated state of the adult thyroid. Disruption of both alleles of the NKX2-1 gene in mice results in complete absence of both pituitary and thyroid glands, whereas disruption of PAX8 results in a small thyroid that lacks follicles. FOXE1 null mice exhibit cleft palate and either a sublingual or completely absent thyroid gland. While thyroid transcription factors are essential for thyroid development, mutations in the homologous genes account for at most 2% cases of thyroid dysgenesis in humans, suggestive of the possibility of non-Mendelian mechanisms of thyroid dysgenesis.

THYROID HORMONE

METABOLISM OF DIETARY IODINE

Iodine is an essential micronutrient, required as a mandatory structural and functional element of thyroid hormones. Iodine in our diet is taken up by the thyroid cell and incorporated into thyroid hormones. In the thyroid gland, iodine is bound to the amino acid tyrosine as monoiodothyronine (MIT), diiodothyronine (DIT), triiodothyronine (T3), and thyroxine (T4).

Natural sources of iodine include fish and seafood, some vegetables, and drinking water. In most countries, table salt is fortified with iodine.

Dietary iodine is absorbed by the ...

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