Fetal thyroid function: diagnosis and management of fetal thyroid disorders.

The fetal hypothalamic-pituitary-thyroid axis develops independently of the maternal axis, but it is dependent on the maternal-placental system for adequate supply of iodide substrate. This iodide is supplied by direct transfer of maternal plasma iodide and by placental deiodination of T4. In addition, although placental transport of iodothyronines is limited, significant maternal-fetal transfer of T4 occurs, accounting for approximately 30% of the average 10 ug/dL serum-T4 concentration in fetal-cord blood at term. Current information suggests that this maternal contribution to the fetal-T4 levels is important for normal fetal maturation, particularly of the central nervous system. Combined maternal-fetal hypothyroxinemia can lead to irreversible fetal central nervous system damage. The timing of this fetal T4 dependency is not clear. It may be important in the first half of gestation, before the fetal thyroid gland is capable of T4 production, as well as the latter half of gestation when thyroid hormone effects on multiple organ systems are developing. Management of fetal thyroid dysfunction requires normalization of maternal serum T4 concentrations, avoidance or careful monitoring of potentially goitrogenic drug effects in the fetus, and in some instances, direct or indirect fetal therapy. In most cases fetal hypothyroidism is sporadic and undetected, and prognosis for normal growth and development is excellent if the mother is euthyroid and the hypothyroid state is detected and adequately treated at birth. Fetal treatment by intraamniotic thyroxine injection has been provided in cases of inadvertent maternal radioiodine treatment of Graves' disease between 10 and 20 weeks gestation and for fetal goiter detected by ultrasound. Effective treatment of fetal hyperthyroidism in pregnant women with high titers of thyroid stimulating autoantibody is possible by judicious administration of antithyroid drugs to the mother. Management of the hyperthyroid state in the neonate also is essential.