Prediction and therapy of intrauterine and late-onset neonatal hyperthyroidism.

These studies in a mother and child describe the effects of multiple antibodies directed against the TSH receptor that influenced thyroid function in the fetus and infant. Blood was taken periodically for 6 months from a child (C3) whose mother (M) was known to have in her serum immunoglobulin G (IgG) that contained thyroid-stimulating antibody (TSAb), an inhibitor of TSAb and TSH binding and action, and an enhancer of TSH binding to its receptor, the last activity presumed to enhance both TSH and TSAb action. We correctly predicted that C3 and an older sibling, C2, would have delayed onset of hyperthyroidism (approximately 45 days of age) due to interaction of these antibodies. In addition, in both C2 and C3, fetal hyperthyroidism in the second trimester was postulated, and therefore, M was given propylthiouracil from then until term (C2) or 8 months (C3), with associated return of the fetal heart rate to normal in the one fetus (C3) in whom this was monitored. IgG was purified from C3's serum samples and tested for TSAb activity using human thyroid cells in monolayer culture and its ability to alter binding of [125I]TSH to human thyroid cell membranes. In the TSAb assays, samples obtained from birth to 4 months of age produced a negative dose response, and those obtained from 4-6 months showed a positive dose response. The effect on the binding of [125I]TSH was enhancement with all IgG obtained for 6 months, except that for the first 52 days a high concentration was inhibitory. The combined clinical and assay data are compatible with the following interpretations. M's IgG contained TSAb and both an inhibitor and an enhancer of that activity, the total effects varying at different times. In the second trimester, the net effect of transplacentally transferred IgG was to induce hyperthyroidism. At birth and perhaps during the third trimester, the inhibitor of TSAb prevented hyperthyroidism; from about 45 days of life, the enhancing effect facilitated TSAb action to produce hyperthyroidism until maternal IgG was completely cleared from the infant's circulation at about 7 months of age.