THYROIDAL CONGENITAL HYPOTHYROIDISM
B1. Ontogeny of the Thyroid Gland
The thyroid gland is the first endocrine gland to appear during embryonic development. The gland develops from a median endodermal thickening in the floor of the primitive pharynx. This placode (median anlage) develops into a diverticulum that grows caudally. By seven weeks of gestation, the human thyroid gland has usually reached its final site in the neck. Experiments with knock-out mice show that the transcription factors NKX2.1, FOXE1 and PAX8 are crucial for thyroid development. [76] Hypoplasia caused by inactivation of the TSH receptor is a later phenomenon.[77]
Defects in NKX2.1
The transcription factor NKX2.1 (TTF-1) is a member of a protein family essential for developmental processes. The NKX2.1 gene is localized on chromosome 14q13 and is expressed in thyroid, lung and several structures of the forebrain. Mice missing the NKX2.1 gene are stillborn, lack the thyroid gland, the pituitary gland, lung parenchyma, and show extensive defects in brain development.[78] Mutations in the NKX2.1-gene are not a frequent cause of CH but result in a syndrome combining a variable degree of congenital hypothyroidism, choreoathetosis, muscular hypotonia and pulmonary problems. [79] [80] [81] [82] The unfavorable outcome of these patients probably does not reflect the hypothyroid state but is most likely due to impaired NKX2.1 expression in the central nervous system. In mice NKX2.1 haploinsufficiency results in hypothyroidism caused by the concomitant reduced expression of the TSH-receptor. [83] Hypothyroidism can range from thyroid agenesis with severe hypothyroidism to a moderate hypoplastic gland with mild hypothyroidism to complete euthyroidism.
Thyroidmanager.org - U of Chicago course
