Development of the thyroid.

Abstract

The fetal hypothalamic-pituitary-thyroid axis develops autonomously of maternal influence. System ontogenesis begins with the appearance and histological development of the thyroid and pituitary glands followed by development of the hypothalamus and the pituitary portal vascular system. Hypothalamic-pituitary control of thyroid function matures during the last half of human fetal development. Thyroid hormones undergo several types of biochemical transformations in tissues, including deiodination, side-chain metabolism, and conjugation with sulphate or glucuronide. Enzyme-mediated monodeiodination is the most important pathway. The first step in T4 metabolism is either outer-ring monodeiodination to active T3 or innerring monodeiodination to inactive rT3. Most T4 is metabolized to rT3 in fetal tissues and/or placenta and rT3 is the major circulating T4 metabolite in the fetus. Selective tissues, such as brain, can monodeiodinate T4 to T3, and this T3 is available for local action. Nuclear thyroid hormone receptors mature at different times in different tissues. Receptors appear earlier in brain than in liver and local T3 production and action may be important in fetal brain development. Most thyroid hormone actions, however, appear in the perinatal period, and infants with thyroid agenesis appear normal at birth and develop normally with prompt neonatal diagnosis and treatment. Premature infants, particularly those less than 30-32 weeks' gestational age, have an immature thyroid system and manifest a state of transient hypothalamic-pituitary TSH deficiency. This does not require treatment. Infants with primary hypothyroidism, either due to thyroid dysgenesis or to thyroid dyshormonogenesis, by contrast, require prompt diagnosis and treatment. Rarely an infant is born with permanent TSH deficiency with or without other pituitary hormone deficiencies. These infants also require prompt treatment. Mothers with thyroid disease or a history of thyroid disease and with IgG autoantibodies to thyroid gland TSH receptors may deliver infants with hypothyroidism or hyperthyroidism due to transplacental passage of the receptor-blocking or receptor-stimulating autoantibodies. These infants also require careful evaluation and management.