THE MECHANISMS OF TRANSIENT HYPOTHYROXINEMIA IN INFANTS BORN TO MOTHERS WITH GRAVES-DISEASE

Transient hypothyroxinemia in infants born to mothers with Graves' dis ease is a unique disorder first reported by us in 1988. Most mothers o f these infants have had no treatment, are diagnosed as having thyroto xicosis during the last trimester, or were not well controlled during pregnancy. These infants are believed to have transient central hypoth yroidism, the mechanisms of which have not been elucidated. We measure d TSH-receptor antibody activities in maternal serum and blood thyroxi ne (T-4) (free thyroxine, FT4) and TSH levels in blood dried on filter paper at 1, 3, and 5 d of age in 114 infants born to mothers with Gra ves' disease. The 114 infants were retrospectively divided into three groups according to the clinical course and thyroid function data: gro up G, neonatal thyrotoxicosis; group T, transient hypothyroxinemia; an d group E, euthyroid. In group T, the dried blood T-4 (FT4) level from cord blood and/or 1 d of age blood was 6.0 +/- 2.3 mu g/dL (0.92 +/- 0.52 ng/dL), a value significantly higher than that at 5 d of age (3.6 +/- 1.0 mu g/dL; 0.38 +/- 0.18 ng/dL) (p = 0.025 in T-4, p = 0.042 in FT4). In contrast, these levels were significantly lower at birth rel ative to 5 d in group G (p = 0.0001 in T-4) and not significantly chan ged in group E. The TSH level of cord blood and/or 1-d-old blood in gr oup T was significantly lower than that of group E (p = 0.0006). Moreo ver, the TSH levels in response to thyrotropin-releasing hormone were blunted in most infants in group T. Bone maturation was not delayed in group T, compared with euthyroid infants. The higher blood T-4 (FT4) levels at birth, relative to 5 d in group T, suggested that the fetal T-4 level was higher than that of the newborn period. The fetal T-4 le vel might have been elevated owing to transfer of T-4 from mother to f etus during the last trimester when the mother's thyroid function was elevated and consequently the fetal pituitary-thyroid axis was suppres sed. Although the serum T-4 (FT4) levels were decreased after birth, T SH levels were not elevated, probably because the pituitary-thyroid ax is was suppressed. This may be the reason for the transient hypothyrox inemia with a normal TSH level in infants born to mothers with poorly controlled Graves' disease. Weak maternal thyroid-stimulating antibody activities and differences in sensitivity of the thyroid gland to TSH -receptor antibodies may contribute to this unique disorder.