title: The safety of methimazole and propylthiouracil in pregnancy: a systematic review.
abstract: BACKGROUND
  Hyperthyroidism is one of the most common endocrine disorders in pregnant women, and it can severely complicate the course and outcome of pregnancy. Methimazole (MMI) and propylthiouracil (PTU) are the standard anti-thyroid drugs used in the treatment of hyperthyroidism in pregnancy. Traditionally, MMI has been considered to have clearer evidence of teratogenicity than PTU. Recent studies suggest that PTU can be hepatotoxic, leading to a United States Food and Drug Administration "black box alert." We wished to systematically review the effects of PTU and MMI during pregnancy, and to compare maternal and fetal safety.
  
  
  METHODS
  We conducted a systematic search of PubMed, EMBASE, TOXNET, TOXLINK, DART, Medscape, EBSCO, and Google. Both English and non-English publications were included. We excluded studies using anti-thyroid therapies other than PTU and MMI, studies not allowing interpretation of results, and abstracts of meetings.
  
  
  RESULTS
  Overall, insufficient statistical power precluded determination of accurate rates of either MMI teratogenicity or PTU hepatotoxicity in cohort studies. However, a case-control study helped identify the relative risk of MMI-induced choanal atresia. A second case-control study failed to show that aplasia cutis congenita is associated with MMI. PTU has been associated with a rare but serious form of hepatic failure.
  
  
  CONCLUSIONS
  MMI causes a specific pattern of rare teratogenic effects after first trimester exposure, while PTU therapy may be followed by rare but severe hepatotoxic sequelae. It is therefore appropriate to use PTU to treat maternal hyperthyroidism during the first trimester of pregnancy, and to switch to MMI for the remainder of the pregnancy.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto ON; Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Rinat
authors.initials: R
authors.lastname: Hackmon
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto ON; Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Monica
authors.initials: M
authors.lastname: Blichowski
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto ON; Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology; D013956:Antithyroid Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D006980:Hyperthyroidism / Q000150:complications* / Q000188:drug therapy*; D008713:Methimazole / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011261:Pregnancy Trimester, First; D011441:Propylthiouracil / Q000009:adverse effects*
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil