ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2018) 15 3.9 | DOI: 10.1530/ey.15.3.9

ESPEYB15 3 Thyroid Graves’ disease (2 abstracts)

3.9 Antithyroid drugs and congenital malformations: a nationwide Korean cohort study

Seo GH , Kim TH & Chung JH


Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea


To read the full abstract: Ann Intern Med 2018;168:405-413

Newly-diagnosed or pre-existing Graves’ hyperthyroidism affects up to 1% of all pregnant women and is associated with adverse effects on pregnancy outcome and offspring. Clinical care of women with hyperthyroidism during pregnancy remains challenging as antithyroid drugs (ATD) can be harmful to the fetus.

Here, Seo et al. analysed data from the Korean National Health Insurance Database on about 2.9 million mother-child pairs, to evaluate the association between first trimester ATD use and congenital malformations. The key findings of this important paper are: 1) increased risk for congenital malformations was identified for both methimazole (MMI) and propylthiouracil (PTU), but MMI was associated with higher risk for congenital malformations than PTU, confirming previous studies1. 2) Most importantly, and for the first time, the authors provide evidence for a dose dependent association of MMI with congenital malformations, further supporting caution with MMI use if a pregnancy is planned. Further studies are needed for more precise teratogenic threshold definition of MMI. 3) Women who switched from MMI to PTU during early pregnancy or even in the 3 months before conception had a similar risk for MMI associated congenital malformations as mothers who remained on MMI. This finding is of great interest and needs to be replicated by future studies.

In the context of their new findings, the authors discuss the current American Thyroid Association (ATA) guideline that recommends to switch from MMI to PTU during early pregnancy to avoid MMI associated malformations2. They argue against an ATD switch because it exposes the embryo for a certain period to two different teratogens, further increasing malformation risk. The safest option seems to be to switch as early as possible from MMI to PTU in women who plan pregnancy. This paper provides important new information concerning risk of malformations and ATD use in pregnancy.

1. Andersen SL, Olsen J, Wu CS, Laurberg P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab 2013;98:4373-4381.

2. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2017;27:315-389.

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