Treatment of Graves’ hyperthyroidism with thionamides: a position paper on indications and safety in pregnancy
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Graves’ disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves’ hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI.
Methods and results
Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter.
This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.
KeywordsPregnancy Embryopathy Methimazole Propylthiouracil Graves’ diseases Pancreatitis
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
No informed consent.
- 4.Su DW, Zou DJ (2008) One case of methimazole induced acute pancreatitis. Chin J Pract Med 24:2915Google Scholar
- 8.Agito K, Manni A (2015) Acute pancreatitis induced by methimazole in a patient with subclinical hyperthyroidism. J Investig Med High Impact Case Rep 3(2):2324Google Scholar
- 17.Gianetti E, Russo L, Orlandi F, Chiovato L, Giusti M, Benvenga S, Moleti M, Vermiglio F, Macchia PE, Vitale M, Regalbuto C, Centanni M, Martino E, Vitti P, Tonacchera M (2015) Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy. J Endocrinol Invest 38:977–985PubMedCrossRefGoogle Scholar
- 18.Laurberg P, Andersen SL (2015) Graves’-Basedow disease in pregnancy. New trends in the management and guidance to reduce the risk of birth defects caused by antithyroid drugs. Nuclearmedizin 54(3):106–111Google Scholar
- 31.Dutertre JP, Jonville AP, Moraine C, Autret E (1991) Aplasia cutis after exposure to carbimazole in utero. J Gynecol Obstet Biol Reprod (Paris) 20:575–576Google Scholar
- 41.Sargent KASJE, Mallozzi AE, Khandelal M, Quashie C, Schneider AS (1994) Apparent scalp-ear-nipple (Finlay) syndrome in a neonate exposed to methimazole in-utero. Am J Hum Genet 55:A312Google Scholar
- 45.Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, Kosuga Y, Suzuki M, Matsumoto M, Kunii Y, Watanabe N, Mukasa K, Ito K (2012) Treatment of Graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab 97:2396–2403PubMedCrossRefGoogle Scholar
- 51.Yoshihara A, Noh JY, Watanabe N, Mukasa K, Ohye H, Suzuki M, Matsumoto M, Kunii Y, Suzuki N, Kameda T, Iwaku K, Kobayashi S, Sugino K, Ito K (2015) Substituting potassium iodide for methimazole as the treatment for Graves’ disease during the first trimester may reduce the incidence of congenital anomalies: a retrospective study at a single medical institution in Japan. Thyroid 25(10):1155–1161PubMedCrossRefGoogle Scholar
- 52.Seo GH, Kim TH, Chung JH (2018) Antithyroid drugs and congenital malformations: a nationwide Korean study. Ann Intern Med 17:1–9Google Scholar