Graves Hyperthyroidism and Pregnancy: A Clinical Update

Komal Patil-Sisodia, MD; Jorge H. Mestman, MD


Endocr Pract. 2010;16(1):118-129. 

In This Article

Historical Background

Antithyroid drugs are now considered the mainstay of therapy for hyperthyroidism during pregnancy to help prevent perinatal complications. Before the introduction of thiouracil drugs for the treatment of hyperthyroidism, fetal loss in pregnant women affected with hyperthyroidism was 45%.[4] Shortly thereafter, fetal mortality was 4% in patients treated with potassium iodide and subtotal thyroidectomy.[5]

Antithyroid drugs were first introduced by Astwood in 1951, when he reported that 19 pregnant women had been treated with propylthiouracil (PTU) alone with no fetal or maternal mortality.[6] A literature review by Piper and Rosen in 1954 showed that the perinatal mortality of infants born to mothers whose condition was managed with antithyroid drugs was 7.2%, but the incidence of neonatal goiters was 19%.[7] Death due to severe tracheal compression by the goiter and suffocation was reported in 1 case. Withdrawal of the antithyroid drugs 2 to 3 months before delivery prevented the development of neonatal goiter.

Several subsequent studies showed a higher incidence of neonatal goiter in patients treated with iodine followed by subtotal thyroidectomy, but it remained the recommended treatment of choice until the 1960s and 1970s. Later studies showed that appropriate titration of PTU and addition of thyroid hormone extract to keep patients clinically euthyroid resulted in good outcomes during pregnancy and no neonatal goiter.[8] Burrow suggested that goiter formation in the neonates was due to overtreatment of the mothers with antithyroid drugs, rendering them hypothyroid.[1] In 1967, a symposium on hyperthyroidism sponsored by The Endocrine Society concluded that all forms of treatment—surgery in the second trimester, antithyroid drugs, and antithyroid drugs plus thyroxine (T4)—were acceptable in the management of hyperthyroidism in pregnancy.[9] In 1974, Mestman et al documented that the use of antithyroid medication plus thyroid hormone resulted in the use of higher daily dosages of antithyroid drugs to render a patient euthyroid when compared with use of antithyroid drugs alone.[10] Over the last 40 years, the treatment recommendations have favored the use of medical therapy with antithyroid drugs over surgery.