Graves Hyperthyroidism and Pregnancy: A Clinical Update

Komal Patil-Sisodia, MD; Jorge H. Mestman, MD


Endocr Pract. 2010;16(1):118-129. 

In This Article


Effective treatment of hyperthyroidism during pregnancy is necessary to prevent maternal, fetal, and neonatal complications. Antithyroid drugs remain the treatment of choice for hyperthyroidism during pregnancy. The goal is to use the lowest possible dosage of antithyroid medication necessary to maintain the free T4 index in the upper one-third of the reference range or just above the normal range. Momotani et al showed that fetuses of mothers treated with antithyroid drugs up to the time of delivery had low T4 levels despite normal T4 levels in their mothers.[27] Excessive dosages of antithyroid drugs may affect fetal thyroid function, with the development of hypothyroidism and/or goiter. At the initiation of therapy, women should be monitored every 2 weeks for titration of antithyroid drug dosage; the dosage should be decreased with the improvement of symptoms and signs (eg, weight gain and normalization of pulse rate) and free T4 index. Once the free T4 index target is achieved, thyroid tests may be repeated every 2 to 4 weeks to keep the patient's free T4 index in the upper reference range with the lowest possible dosage of antithyroid drug. Serum TSH may remain suppressed throughout pregnancy; the presence of detectable TSH is an indication to decrease the antithyroid drug dosage. Patients who achieve euthyroidism with minimal dosages of antithyroid drugs and have a short duration of symptoms, undetectable or low TRAb titers, and small goiters may be able to discontinue antithyroid drugs during the last 4 to 8 weeks of pregnancy. Discontinuing medication before 32 weeks' gestation is not recommended because of the possibility that hyperthyroidism may recur. The initial recommended PTU dosage is 100 to 450 mg daily, depending on symptoms and results of thyroid function tests. The total dosage is divided into 3 daily doses. Methimazole can be initiated at 10 to 20 mg daily in 1 dose (Fig. 2).

Figure 2.

A representative example of management of hyperthyroidism in pregnancy. This patient is hyperthyroid at time of conception on methimazole (MMI), 10 mg daily. When pregnancy is diagnosed, MMI is discontinued and propylthiouracil (PTU) is added at a dosage of 150 mg three times daily. By the end of the first trimester, PTU is discontinued and MMI is given at a dosage of 20 mg daily. By week 20, the free thyroxine (T4) index is almost normal, and the MMI dosage is reduced to 10 mg. By week 26, the free T4 index is in the upper reference range and thyrotropin remains suppressed. The MMI dosage is reduced to 5 mg daily. The free T4 index remains in the upper reference range, and by week 34, MMI is discontinued, and the patient remains euthyroid until delivery. The gray band indicates reference range. LNMP, last normal menstrual period.

β-Adrenergic blockers, such as propranolol, 10 to 40 mg every 4 to 6 hours, or atenolol, 25 to 50 mg daily, are also recommended for treatment of hyperadrenergic symptoms present in hyperthyroidism, but should be discontinued once symptoms resolve or within the first few weeks of treatment. One publication reported an increased incidence of spontaneous abortion with prolonged use of propranolol in combination with antithyroid drugs vs antithyroid drugs alone.[28]

Subtotal thyroidectomy in the second trimester of pregnancy remains an effective therapy if medical therapy fails, the patient cannot tolerate treatment, the patient has a very large goiter requiring high dosages of antithyroid drugs, or the patient is allergic to both antithyroid drugs.[29] Resistance to the therapeutic effect of antithyroid drugs is extremely rare and, in most cases, is due to poor adherence to the medication regimen. Patients may be treated with intravenous β-antagonists at the time of surgery to achieve a goal heart rate of 80 to 100 beats per min before and during surgery. A short course of iodine in preparation of surgery is not contraindicated. Patients undergoing subtotal thyroidectomy should have TRAb measured because of the potential risk of fetal hyperthyroidism when antithyroid drugs are discontinued after surgery in mothers with high TRAb titers.

The use of iodine therapy in addition to antithyroid medications has fallen out of favor because of higher rates of neonatal goiter and hypothyroidism. In one study of Japanese women with mild hyperthyroidism, lower iodine dosages (6–40 mg daily) resulted in elevated TSH levels in 2 of 35 neonates without the development of goiter; the mothers remained slightly hyperthyroid at the time of delivery.[30] This therapy remains limited to the treatment of thyroid storm or for preparation for thyroidectomy.

Radioactive iodine therapy is contraindicated in pregnancy and lactation. A pregnancy test is mandatory for any woman of childbearing age who is receiving either diagnostic or therapeutic doses of radioactive iodine. Stoffer and Hamburger described a group of women who inadvertently received 131I after 10 weeks' gestation. The incidence of spontaneous abortions and other neonatal abnormalities, such as sudden infant death syndrome and biliary atresia, was not increased when compared with the occurrences in pregnant women who did not receive 131I. However, a higher rate of transient hypothyroidism and global developmental delay was observed in offspring of mothers who became hypothyroid after receiving 131I when compared with rates in the general population.[31]