OBJECTIVESAfter completing this article, readers should be able to:1. Describe the etiology of transient and persistent neonatal hyperthyroidism. 2. Delineate the diagnostic tests for thyroid-stimulating hormone receptor antibodies. 3. Develop a treatment plan for fetal and neonatal hyperthyroidism and a management plan for subsequent pregnancies. 4. Provide guidelines for breastfeeding when the mother is receiving antithyroid medications. 5. Describe the long-term risks of neonatal hyperthyroidism.
HistoryThe first clinical description of neonatal hyperthyroidism was published in 1912, and the discovery of the transplacental passage of thyroidstimulating immunoglobulins (TSI) provided an understanding for the etiology of this condition in 1964. There were, however, a few cases of persistent neonatal hyperthyroidism, initially described in 1976, that were inconsistent with the transient clinical course expected with a maternally acquired antibody. The etiology of persistent neonatal hyperthyroidism was clarified by the discovery of an activating germ-line mutation in the thyroid-stimulating hormone (TSH) receptor in 1995.
Maternal Autoimmune Thyroid DiseaseWhen a mother has autoimmune thyroid disease, fetal and neonatal hyperthyroidism result from transplacental passage of TSI. The mother usually has a history of hyperthyroidism, but neonatal hyperthyroidism also has been reported in mothers who have hypothyroidism due to Hashimoto thyroiditis. The clinical status of the mother does not determine the infant's risk for hyperthyroidism. The mother may have been treated with 131 I or a subtotal thyroidectomy in the past and may be euthyroid or she may be receiving thyroid replacement therapy at the time of her pregnancy, but she still can be producing high titers of TSI. In a review of neonatal hyperthyroidism, mothers were clinically hyperthyroid during pregnancy in only 18 of 38 cases (47%). The prevalence of clinical hyperthyroidism in pregnancy has been reported to be 0.1% to 0.4% and is the most common endocrine disorder during pregnancy after diabetes. Clinical fetal and neonatal hyperthyroidism has been reported to occur in 1% to 5% of pregnancies complicated by Graves disease. It is common for fetal and neonatal hyperthyroidism to recur in subsequent pregnancies.Why is there such a low incidence of neonatal hyperthyroidism with all the mothers who have autoimmune hyperthyroidism producing TSI? Several pregnancy-related immunologic events work concomitantly to lower the fetal/neonatal risk for hyperthyroidism. The TSH receptor is present in the fetus at 12 weeks of gestation, but before 15 weeks of gestation, fetal immunoglobulins are only 5% to 8% of maternal levels, so little TSI crosses the placenta. By 30 weeks of gestation, when fetal immunoglobulin levels are equal to maternal levels, there is a decrease in TSI concentrations due to immune suppression that occurs during pregnancy. When measured serially in 15 mothers who had hyperthyroidism, TSI levels decreased from 280% in the first trimester to 130% ...
