Authors’ Response: Severe Embryopathy and Exposure to Methimazole in Early Pregnancy

David S. Cooper and Susan Mandel

Sinai Hospital of Baltimore and Johns Hopkins University School of Medicine (D.S.C.), Baltimore, Maryland; and University of Pennsylvania School of Medicine (S.M.), Philadelphia, Pennsylvania

Address requests for reprints to: David S. Cooper, M.D., Division of Endocrinology, Sinai Hospital of Baltimore, Hoffberger Building, Suite 56, 2401 West Belvedere Avenue, Baltimore, Maryland 21215.

To the editor:

We thank F. A. Karlsson and colleagues for their letter and the additional case report of methimazole exposure and embryopathy. In our view, there is little doubt that there is an association between methimazole usage and congenital abnormalities. The real issue is how to balance the care of hyperthyroid women with the potential for fetal malformations. Certainly, the frequency of methimazole-associated embryopathy is low: assuming that there are 4 million births per year in the United States, and that 1 in 500 pregnancies is associated with Graves’ disease, this means that there are 8,000 babies born yearly who have potentially been exposed to antithyroid drugs. If 90% are exposed to propylthiouracil (PTU) (as the preferred drug in pregnancy), this leaves roughly 800 infants exposed to methimazole annually. Because there are only three case reports of birth defects in association with methimazole from the United States over the last decade, the frequency of this problem seems to be in the range of 1/1,000–1/10,000 exposures. Given all of the advantages of methimazole over PTU, particularly better patient compliance, many thyroidologists prefer methimazole for all nonpregnant patients with thyrotoxicosis. If fear of birth defects is brought into the equation, many young women may reject methimazole outright, to the detriment of patient care.

As we indicated in our review, PTU is preferred over methimazole in pregnancy, and if a woman taking methimazole becomes pregnant, switching to PTU seems reasonable, in light of the likely association of methimazole with aplasia cutis and other birth defects. On the other hand, if a pregnant woman were allergic to PTU, we would recommend switching to methimazole, rather than sending her to surgery.

We disagree with the suggestion of Karlsson et al. that women of childbearing age should be given methimazole only if they promise to use birth control. Oral contraceptive use has its own associated risks, such as an increased incidence of venous thrombosis and embolism. Furthermore, the rarity of the methimazole-associated congenital malformations makes the risk to benefit ratio uncertain. We strongly urge physicians to inform women (and men) of all the potential risks and benefits of all forms of therapy of hyperthyroidism, so that an informed decision can be reached with full participation by the patient.

Received September 25, 2001.





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