What is important in managing Graves' disease (Hyperthyroidism due to Graves' disease) during pregnancy?

From the Guidelines

Management of Graves' disease during pregnancy requires careful monitoring and treatment to protect both mother and fetus, with the goal of maintaining maternal free T4 levels in the upper normal to slightly elevated range using the lowest effective dose of antithyroid medication. The preferred treatment is propylthiouracil (PTU) during the first trimester, switching to methimazole for the remainder of pregnancy due to PTU's risk of liver damage and methimazole's risk of birth defects in early pregnancy 1. Typical starting doses are PTU 50-150 mg three times daily or methimazole 5-20 mg daily, adjusted based on thyroid function tests performed every 2-4 weeks initially, then every 4-6 weeks once stable.

Key Considerations

• Beta-blockers like propranolol (10-40 mg three to four times daily) can be used short-term for symptom control 1.
• Regular fetal ultrasound monitoring is essential to check for growth, heart rate, and signs of thyroid dysfunction.
• After delivery, close monitoring must continue as there's risk of postpartum thyroid dysfunction, and medication doses often need adjustment.
• Breastfeeding is generally safe with low doses of antithyroid medications.
• Women with Graves' disease should be monitored for normal heart rate and appropriate growth; unless problems are detected; ultrasound screening for fetal goiter is not necessary 1.

Treatment Approach

• Thyroidectomy should be reserved for women who do not respond to thioamide therapy 1.
• Treatment with iodine 131 (I-131) is contraindicated in pregnant women, and women should not breastfeed for four months after treatment with I-131 1.
• The newborn's physician needs to be aware that the mother has Graves' disease because of the associated risk of neonatal thyroid dysfunction 1.

From the FDA Drug Label

In pregnant women with untreated or inadequately treated Graves’ disease, there is an increased risk of adverse events of maternal heart failure, spontaneous abortion, preterm birth, stillbirth and fetal or neonatal hyperthyroidism Because propylthiouracil crosses placental membranes and can induce goiter and cretinism in the developing fetus, it is important that a sufficient, but not excessive, dose be given during pregnancy. In many pregnant women, the thyroid dysfunction diminishes as the pregnancy proceeds; consequently a reduction of dosage may be possible In some instances, antithyroid therapy can be discontinued several weeks or months prior to delivery. Given the potential for maternal hepatotoxicity from propylthiouracil, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters during pregnancy.

Key considerations in managing Graves' disease during pregnancy:

• Monitoring thyroid function to avoid excessive doses of antithyroid medication
• Adjusting doses as thyroid dysfunction diminishes during pregnancy
• Considering switching from propylthiouracil to methimazole in the second and third trimesters due to potential maternal hepatotoxicity
• Being aware of the potential risks of untreated or inadequately treated Graves' disease, including maternal and fetal complications 2 3 3

From the Research

Importance of Managing Graves' Disease in Pregnancy

• The management of Graves' disease during pregnancy is crucial to prevent maternal, obstetrical, and fetal complications 4, 5.
• Hyperthyroidism in pregnancy can lead to fetal hyper- or hypothyroidism, neonatal dysthyroidism, premature birth, and pre-eclampsia 5.

Treatment Options

• Antithyroid drugs are the first line treatment for hyperthyroidism due to Graves' disease in pregnant women 4, 6.
• Propylthiouracil (PTU) is the recommended treatment during the first trimester of pregnancy due to the increased risk of congenital malformations associated with carbimazole/methimazole 4, 6, 7.
• After the first trimester, consideration should be given to switching to carbimazole/methimazole 4.
• The lowest possible dose of PTU should be used to minimize the risk of fetal goiter and mental and physical retardation 8.

Monitoring and Follow-up

• Patients should be followed at 3-week intervals if progress is satisfactory, and more often if necessary 8.
• Thyroid function should be monitored by the free T4 assay 8.
• Fetal monitoring should be initiated in a multidisciplinary framework and continued throughout pregnancy 5.
• Neonatal monitoring is also crucial if the mother still shows anti-TSH-receptor antibodies at the end of pregnancy or underwent antithyroid treatment 5.
• The risk of recurrence of hyperthyroidism in the weeks following delivery requires maternal monitoring 5.