Antithyroid drugs should be avoided early in pregnancy: study

Last Updated: 2016-02-11

By Will Boggs MD

NEW YORK (Reuters Health) - The use of antithyroid drugs should be avoided in early pregnancy to reduce the likelihood of birth defects, researchers from Denmark report.

"Physicians treating young women with antithyroid drugs should be aware of the importance of a possible future pregnancy," Dr. Stine Linding Andersen and Dr. Peter Laurberg from Aalborg University Hospital told Reuters Health by email. "It is mandatory to discuss with such women that pregnancy should be detected as early as possible."

Hyperthyroidism can adversely affect the health of pregnant women and the development of the fetus, but its treatment with antithyroid drugs in early pregnancy can cause birth defects. Current guidelines favor the use of propylthiouracil (PTU) in early pregnancy, then switching to methimazole/carbamizole (MMI/CMZ) later in pregnancy.

Dr. Andersen and colleagues used data from the Danish Medical Birth Register, the Danish National Prescription Register, and the Danish National Hospital Register to examine the frequency of birth defects, agranulocytosis, and liver failure associated with the use of these drugs in the general population and in pregnant women.

Of nearly 30,000 individuals prescribed antithyroid drugs, most received MMI/CMZ (n=27,281) and far fewer received PTU (n=5,895).

MMI-associated side effects in the general population were twice as common as PTU-associated side effects, but this related to the nearly five-times more frequent use of MMI, according to the January 27 online report in the Journal of Clinical Endocrinology and Metabolism.

The frequency of agranulocytosis was significantly higher with PTU (0.27%) than with MMI/CMZ (0.11%, p=0.02), whereas the frequency of liver failure did not differ significantly between PTU (0.05%) and MMI/CMZ (0.03%, p=0.4).

Antithyroid drug-associated agranulocytosis and liver failure were less common in pregnant women (five and five cases/10,000 exposed to antithyroid drugs, respectively) than in the general population (16 and three cases/10,000 exposed, respectively).

Seventy-five children had birth defects associated with maternal use of antithyroid drugs in 2,206 pregnancies (a rate of 340 cases/10,000 exposed).

"We advise women who are treated with antithyroid drugs to buy and have self-administered pregnancy tests (only a few dollars per test) and to perform such test if pregnancy is a possibility," Dr. Andersen and Dr. Laurberg said. "If a pregnancy test is positive, the woman should contact her thyroid physician and take no more antithyroid drugs before such contact."

"If the physician considers that the woman is in remission of hyperthyroidism, we recommend to observe without antithyroid drug therapy and to perform weekly control of thyroid function tests until the second trimester of pregnancy," they explained.

"If antithyroid drug therapy is considered necessary in early pregnancy, we recommend the use of PTU. If pregnancy is planned, it can be considered to change to PTU therapy even before pregnancy. If treatment is considered necessary after the first trimester of pregnancy, the physician can either continue PTU therapy or shift the woman to MMI/CMZ," they advised.

"The early pregnancy period is just as important for the thyroid physician as the late pregnancy is for the obstetrician," Dr. Andersen and Dr. Laurberg concluded. "Untreated hyperthyroidism may seriously complicate a pregnancy and should always be carefully managed and controlled. However, focus on early detection of pregnancy in women who are treated with antithyroid drugs and evaluation of the clinical indication for the use of antithyroid drugs in early pregnancy may reduce the burden of severe side effects to these drugs in a population."

The authors reported no external funding or disclosures.

SOURCE: http://bit.ly/1KHYWva

J Clin Endocrinol Metab 2016.