Drug therapy for hyperthyroidism in pregnancy: safety issues for mother and fetus

Abstract

Hyperthyroidism (thyrotoxicosis) in pregnancy and the child bearing years is usually attributable to Graves' disease. This is an autoimmune condition in which thyroid-stimulating immunoglobulins (TSI) cause hyperthyroidism. As a rule, pregnancy complicates the management of hyperthyroidism, rather than vice versa. However, patients who remain thyrotoxic during pregnancy are at increased risk of maternal and fetal complications, particularly miscarriage and stillbirth. Therefore, bodyweight loss, eye signs and a bruit over the thyroid gland in a pregnant woman warrant thyroid investigation. Investigations should include measurement of serum free thyroid hormone levels [free thyroxine (T4) and free triiodothyronine (T3)] rather than total T4 and T3 levels, because total T4 and T3 levels may be raised in euthyroid pregnancies due to the presence of increased levels of thyroxine binding globulin (TBG). By 20 weeks' gestational age, the fetal thyroid is fully responsive to TSI and to antithyroid drugs. Maternal T4 and T3 and thyrotropin pass across the placenta in small and decreasing amounts as gestation progresses, but thyrotropin releasing hormone, TSI, antithyroid drugs, iodides and beta-blockers are readily transferred to the fetus from the mother. Hyperthyroidism is usually treated throughout pregnancy with an antithyroid drug, preferably propylthiouracil. The smallest dose which controls the disease is given with careful monitoring of free T4 and T3 levels to minimise the risk of fetal hypothyroidism and goitre. Bilateral subtotal thyroidectomy may be an option for a small number of patients with hyperthyroidism in pregnancy.