Maternal nonthyroidal illness and fetal thyroid hormone status, as studied in the streptozotocin-induced diabetes mellitus rat model

We have used the streptozotocin-induced diabetes mellitus pregnant rat as a model of maternal nonthyroidal illness. We measured the effects of different degrees of diabetes mellitus on maternal body weight, the outcome of pregnancy, circulating glucose, insulin, T-4, T-3, rT(3), and TSH in mother and fetus, T-4 and T-3 in maternal and fetal tissues, and iodothyronine deiodinases in liver, lung, and brain. All of the changes in thyroid hormone status typical of nonthyroidal illnesses were observed in the mothers and were related to the degree of the metabolic imbalances. Most were controlled with a daily insulin dose of 0.5 U/100 g BW. Normalization of maternal placental T-4, however, required higher insulin doses than in other maternal tissues. The number and body weight of the fetuses, their pituitary GH contents, and their thyroid hormone status were severely affected. The total extrathyroidal T-4 and T-3 pools decreased to one third of normal fetal values. T-4 and T-3 concentrations in the fetal brain were lower than normal, and the expected increase in type II 5' deiodinase activity was not observed. The low cerebral T-3 only improved with adequate insulin treatment of the dams. It is concluded that maternal diabetes mellitus, and possibly other nonthyroidal illnesses that impair the availability of intracellular energy stores, may affect fetal brain T-3 when thyroid hormones are essential for normal development.