MATERNAL DIABETES-MELLITUS, A RAT MODEL FOR NONTHYROIDAL ILLNESS - CORRECTION OF HYPOTHYROXINEMIA WITH THYROXINE TREATMENT DOES NOT IMPROVEFETAL THYROID-HORMONE STATUS

Maintenance of normal maternal thyroxinemia prevents severe triiodothy ronine (T-3) deficiency of the fetus with primary thyroid failure (1). We have studied whether thyroxine (T-4) would also protect the fetal brain when maternal hypothyroxinemia is caused by nonthyroidal illness es. We have used the streptozotocin-induced diabetes mellitus pregnant rat as a model of maternal nonthyroidal illness. We measured the effe cts of diabetes mellitus, and of correction of the ensuing maternal hy pothyroxinemia with T-4 as compared to insulin, on maternal body weigh t, the outcome of pregnancy, glucose, insulin, T-4, T-4, reverse T-3, and thyrotropin levels in the maternal and fetal circulation, as well as T-4 and T-3 concentrations in tissues, and iodothyronine deiodinase s in liver, lung, and brain. The diabetic mothers showed changes in th yroid hormone status typical of nonthyroidal illnesses. Thyroid hormon e status of the fetuses was severely affected: the total T-4 and T-3 p ools decreased to one-third of normal values. T-4 and T-3 concentratio ns in the fetal brain were lower than normal and the expected increase in 5'-deiodinase activity was not observed. Although insulin treatmen t avoided or mitigated these changes, the low cerebral T-3 did not imp rove with T-4 treatment Of the maternal hypothyroxinemia. Several find ings indicated that treatment of the severely ill dams with T-4 was ac tually harmful for the outcome of pregnancy. These negative effects we re observed without the expected increase in the maternal or fetal T-3 pools.