Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves' hyperthyroidism

Abstract

Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence. We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T4 (FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M). Neither the fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant differences in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels. These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.