Teratogen update: Antithyroid medications

Birth Defects Res. 2020 Sep;112(15):1150-1170. doi: 10.1002/bdr2.1771. Epub 2020 Aug 1.

Abstract

Objective: Thyroid disorders including hyperthyroidism are common during pregnancy. Untreated hyperthyroidism can result in adverse outcomes for pregnancy.

Methods: Iodine, propylthiouracil (PTU), carbimazole (CMZ), and methimazole (MMI) are common medications for hyperthyroidism treatment. The literature regarding antithyroid medication use in pregnancy and breastfeeding is reviewed.

Results: Animal studies for PTU have suggested congenital anomalies while animal studies for MMI have only indicated adverse outcomes at higher doses than used in humans. Epidemiological studies have noted an increased risk of congenital anomalies for PTU less often than CMZ or MMI but the epidemiological evidence remains mixed. A pattern of anomalies has been described for CMZ and MMI, from both case and epidemiological studies, including choanal atresia, aplasia cutis congenita, and other facial, heart, gastrointestinal, and skin anomalies. Closer examination of cases indicates that a few cases of the anomalies have occurred without exposure to CMZ or MMI and outside of the proposed critical period. PTU has a small risk of hepatotoxicity which rarely results in liver transplantation and death. Some authors have suggested that PTU be prescribed in early pregnancy and switched to MMI in late pregnancy. Untreated hyperthyroidism, from either a lack of medications or switching medications during the first trimester, may also increase the chance of congenital anomalies. Multiple case studies and larger epidemiological studies have failed to provide clear, consistent outcomes for the use of PTU, CMZ, and MMI in pregnancy. MMI and PTU both enter the breastmilk in small amounts.

Conclusion: Additional research is needed to assist in the medical management and exposure counseling of pregnant and breastfeeding women with hyperthyroidism.

Keywords: congenital anomalies; hyperthyroidism; methimazole; pregnancy; propylthiouracil.

Publication types

  • Review

MeSH terms

  • Abnormalities, Drug-Induced* / epidemiology
  • Abnormalities, Drug-Induced* / etiology
  • Animals
  • Antithyroid Agents / adverse effects
  • Female
  • Humans
  • Methimazole / adverse effects
  • Pregnancy
  • Propylthiouracil / adverse effects
  • Teratogens* / toxicity

Substances

  • Antithyroid Agents
  • Teratogens
  • Methimazole
  • Propylthiouracil