Thyrotropin-releasing hormone (TRH), a tripeptide synthesized in the hypothalamus, stimulates the release of pituitarythyroid-stimulating hormone (TSH). Pituitary TSH is a glycoprotein that stimulates the synthesis and release of thyroidhormones by the thyroid gland. Thyroid function developsin three stages. At the end of the first trimester, the glanddescends from the floor of the primitive oral cavity to itsdefinitive position in the anterior lower neck. The hypothalamic-pituitary-thyroid axis becomes functional in the secondtrimester. Peripheral metabolism of thyroid hormones maturesin the third trimester.
Thyroxine (T4), triiodothyronine (T3), and TSH do not cross the placenta in significant amounts. Concentrations in fetal serum reflect primarily fetal secretion and metabolism. Maternal thyroid antibodies, iodides (including radioactive iodides), and medications given to mothers to treat hyperthyroidism (methimazole and propylthiouracil) cross the placenta and affect fetal thyroid function. An infant born prematurely or with intrauterine growth restriction may have an interruption of the normal maturational process and appear to have hypothyroidism by standard tests.
The thyroid gland concentrates iodine and binds it to tyrosine molecules to produce either monoiodotyrosine or diiodotyrosine, with subsequent coupling of two tyrosines, T4 or T3. The major fraction of circulating T3 (approximately two thirds) is derived from peripheral deiodination of T4 to T3, but some is produced by the thyroid gland itself. The conversion of T4 to T3 requires the removal of one iodine from the outer ring