Propylthiouracil Versus Methimazole in Treatment of Graves' Disease During Pregnancy

OBJECTIVE: To evaluate the evidence supporting the use of propylthiouracil (PTU) versus methimazole for the treatment of Graves' disease during pregnancy. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1966–March 2007). Identified articles were then reviewed for additional sources. Search terms included hyperthyroidism, Graves' disease, pregnancy, propylthiouracil, and methimazole. STUDY SELECTION AND DATA EXTRACTION: All clinical trials and case reports that were published in English and reported either subjective or objective outcomes were reviewed. DATA SYNTHESIS: Rationale supporting the use of PTU over methimazole in treatment of Graves' disease during pregnancy is limited. Theories suggesting that PTU has less placental transfer to the fetus than methimazole are not supported by current literature. Studies demonstrating a causal relationship between methimazole use during pregnancy and congenital anomalies and/or fetal hypothyroidism do not exist. CONCLUSIONS: The selection of PTU versus methimazole for the treatment of Graves' disease during pregnancy should not be based solely on the following assumptions: that PTU crosses the placenta less than methimazole, that PTU leads to less fetal hypothyroidism, or that exposure to methimazole during pregnancy leads to decreased intellectual function in children. However, due to a possible association between the use of methimazole during pregnancy and fetal anomalies such as aplasia cutis, esophageal atresia, and choanal atresia, methimazole may be a less desirable first-line treatment for Graves' disease in pregnancy than PTU. Therefore, in the absence of a compelling indication for the use of methimazole, PTU should still be considered as the first-line agent in the treatment of Graves' disease during pregnancy. Methimazole should be considered a viable second choice if the patient is intolerant to PTU, has an allergic reaction to PTU, or fails to become euthyroid while receiving PTU. CONCLUSIONES: La selección de PTU versus metimazole en el tratamiento de enfermedad de Graves durante el embarazo no debe ser basada en la siguiente información: 1que PTU cruza la placenta a un menor grado que metimazole, que PTU se asocia con menos hipotiroidismo fetal, ó que la exposición a metimazole durante el embarazo lleva a una disminución en la función intelectual en niños. Sin embargo, debido a una posible asociación entre el uso de metimazole durante el embarazo y anormalidades fetales tales como aplasia cutis, atresia esofageal y atresia choanal, metimazole podría ser una alternativa de primera línea menos deseable para el tratamiento de enfermedad de Graves durante el embarazo que PTU. Por lo tanto, en la ausencia de indicación contundente para el uso de metimazole, PTU debe considerarse el agente de primera línea en el tratamiento de enfermedad de Graves durante el embarazo. Sin embargo, metimazole puede considerarse un agente alterno si el paciente no tolera el PTU, tiene reacción alérgica a PTU o falla en convertir a eutirodeo con PTU. RÉSUMÉ: Il existe peu de justification à l'utilisation du PTU plutôt que du methimazole. Certaines théories suggérant que le PTU traverse moins la barrière placentaire ne sont pas, à l'heure actuelle, supportées par des évidences. Les études démontrant une relation de cause à effet entre le methimazole et des anomalies congénitales et/ou de l'hypothyroïdisme chez le fétus n'existent pas.