No evidence found from randomised trials for drugs to treat pregnant women with hyperthyroidism

Hyperthyroidism in pregnancy is a rare, serious condition which can increase the risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction. Pregnant women who are hyperthyroid may also develop severe pre-eclampsia or placental abruption. Most of these women have Graves' disease, an autoimmune disease most common in women aged 20 to 40 years. Most pregnant women with hyperthyroidism are diagnosed with thyroid disease prior to conception and will have previously received treatment for the condition. Generally only drug therapy is considered for treating pregnant women with hyperthyroidism. Radioiodine treatment is not used in pregnancy because it destroys the fetal thyroid gland, resulting in permanent hypothyroidism in the newborn.

The main antithyroid drugs used are the thionamides, propylthiouracil (PTU), methimazole and carbimazole. PTU is currently the favoured drug for use in pregnancy, as it is associated with fewer teratogenic effects (scalp lesions) than methimazole. However, since there have been reports of liver damage in people taking PTU, it may be reasonable for pregnant hyperthyroid women to be treated with PTU in the first trimester (to reduce any teratogenic effects of methimazole) and then to change to methimazole.

We did not identify any randomised trials to help inform women and their doctors about which antithyroid drugs are most effective, with the lowest potential for harm.

Authors' conclusions: 

As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

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Background: 

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption.

Objectives: 

To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 September 2013).

Selection criteria: 

We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment).

Data collection and analysis: 

Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently.

Main results: 

No trials were included in the review.