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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.
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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.
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Metabolism of
Dietary Iodine
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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.
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Biosynthesis
of Thyroid Hormone
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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 ...