Diagnosis and Treatment of Graves' Disease During Pregnancy

A Closer Look at Clinical Guidelines

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When hyperthyroidism is not controlled in pregnancy, it's associated with a variety of complications, including miscarriage, pregnancy-induced hypertension, premature birth, low birth weight, intrauterine growth restriction, stillbirth, thyroid storm, and maternal congestive heart failure. Therefore, proper diagnosis and treatment of Graves' disease and hyperthyroidism during pregnancy is essential.

According to the 2011 "Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum," women who have Graves' disease should conceive only after they are euthyroid - defined as having normal thyroid levels. The Guidelines strongly recommend contraception until this is achieved, and recommend that physicians offer counseling to women regarding the implications of treatment on conception plans.

Specifically, the Guidelines recommend that Graves' disease patients receive ablative therapy with surgery or radioactive iodine (RAI), or antithyroid drugs.

The Guidelines recommend surgery for a woman who has high TSH receptor antibody (TRAb) levels and who is planning to get pregnant within two years. The rationale is that the TRAb levels tend to rise after RAI and remain elevated.

If RAI is performed, a pregnancy test should be done 48 hours prior to the RAI administration.

After surgery or RAI, the Guidelines recommend waiting for six months to conceive, to allow for a woman to get on a stable dose of thyroid hormone replacement, with target TSH levels between .3 and 2.5.

For antithyroid drugs, women should be informed about the risks associated with propylthiouracil (PTU) and methimazole, and if these drugs are used, PTU should be used in the first trimester of pregnancy. Methimazole (brand name: Tapazole) poses risks to the fetus if used in the first trimester. The Guidelines also recommend considering the discontinuation of PTU after the first trimester and switching to methimazole, to decrease the risk of liver disease associated with PTU.

Treating Graves' Hyperthyroidism During Pregnancy

The primary treatment for hyperthyroidism during pregnancy is antithyroid drugs, however, from 3% to 5% of patients have drug-related side effects such as allergic reactions and rashes.

Because antithyroid drugs cross the placenta, care needs to be taken with the use of antithyroid drugs during pregnancy. In particular, the main concern is the ability of methimazole to cause congenital malformations - these complications are not associated with the use of PTU. PTU, however, carries a risk of liver toxicity, and the Guidelines recommend that PTU be used in the first trimester, and that patients should switch to methimazole after the first trimester.

Beta blockers are not typically recommended during pregnancy, as they are associated with intrauterine growth restriction, low fetal heart rate, and hypoglycemia in newborns.

Antithyroid Drugs During Pregnancy

The Guidelines recommend that woman taking antithyroid drugs during pregnancy undergo regular monitoring of Free T4 and TSH, so that the Free T4 values remain at, or just above the upper limit of normal, while taking the lowest possible dose of antithyroid drugs. Free T4 and TSH should be measured every two to four weeks at the start of treatment, and every four to six weeks after, to achieve the target blood levels. Typically, because hyperthyroidism often normalizes during pregnancy, antithyroid drugs may end up being discontinued in the third trimester in as many as 20% to 30% of patients.

The Guidelines recommend that women who have high TSH receptor antibody (TRAb) levels continue with antithyroid drug treatment until delivery.

Thyroidectomy for Graves' Disease During Pregnancy

If a woman is allergic to antithyroid drugs, requires high doses to control hyperthyroidism, or is not following her drug therapy, the Guidelines indicate that thyroidectomy should be considered. If thyroid surgery - known as thyroidectomy -- is needed, the optimal time is during the second trimester of pregnancy.

At the time of surgery, the TRAb levels should be measured to assess the potential risk of hyperthyroidism in the fetus. The Guidelines recommend preparation with a beta blocker, and a short course of potassium iodine solution in advance of the thyroidectomy surgery.

Fetal Risks in a Pregnant Women With Active Graves' Hyperthyroidism

There are a number of risks to the fetus of a woman with active Graves' hyperthyroidism, including:

The factors that can affect fetal risk include:

  • poor control of hyperthyroidism throughout pregnancy, which can cause transient central hypothyroidism in the fetus.
  • high doses of antithyroid drugs, which can cause fetal and neonatal hypothyroidism.
  • high levels of serum TRAb between 22 and 26 weeks gestation, which can cause fetal or neonatal hyperthyroidism.

According to the Guidelines, more than 95% of women with Graves' disease have evidence of TRAb, even after ablative therapy, and TRAb should be monitored in pregnant women:

  • with active hyperthyroidism;
  • who previously received RAI treatment;
  • with a history of delivering an infant with hyperthyroidism; and
  • who had a thyroidectomy during pregnancy, to treat hyperthyroidism.

Fetal and neonatal hyperthyroidism occurs in between 1% and 5% of all pregnant women with an active or a past history of Graves' hyperthyroidism, and is associated with a number of complications.

In a pregnant woman who has an active or past history of Graves' disease, TRAb should be measured by 20 to 24 weeks of gestation. According to the Guidelines, a value that is more than three times the upper limit of normal is considered a marker for followup of the fetus, ideally involving a physician specializing in maternal-fetal medicine.

If followup is required, ultrasounds should be performed to monitor fetal development.

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Article Sources
  • Stagnaro-Green, Alex, et. al. "Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum." Thyroid. Volume 21, Number 10, 2011