Should a pregnant woman with Graves' disease on methimazole (antithyroid medication) continue treatment if her Thyroid-Stimulating Hormone (TSH) is low and free T4 is normal with elevated Thyrotropin Receptor Antibody (TRAb) levels?

Continue Methimazole with Dose Adjustment to Maintain Free T4 in High-Normal Range

For a first-trimester pregnant woman with Graves' disease on methimazole who has low TSH, normal free T4, and elevated TRAb, continue methimazole at the lowest dose necessary to maintain free T4 in the high-normal range, as the goal is to prevent maternal and fetal hyperthyroidism while minimizing fetal thyroid suppression. 1

Critical First-Trimester Considerations

The FDA warns that methimazole crosses the placental membranes and can cause rare but serious congenital malformations when used in the first trimester, including aplasia cutis, craniofacial malformations (facial dysmorphism, choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula), omphalocele, and abnormalities of the omphalomesenteric duct. 2

• Despite these risks, untreated or inadequately treated Graves' disease in pregnancy carries significant maternal and fetal risks including maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal or neonatal hyperthyroidism. 2

• The decision to continue methimazole in the first trimester requires balancing the rare risk of congenital malformations against the substantial risks of uncontrolled hyperthyroidism. 2

Why Continue Rather Than Stop

• Stopping methimazole abruptly in a patient with elevated TRAb would risk recurrence of hyperthyroidism, which poses immediate dangers to both mother and fetus. 1

• The presence of elevated TRAb indicates active autoimmune stimulation of the thyroid, meaning the disease is not in remission and will likely worsen without treatment. 3, 4

• The current thyroid status (low TSH with normal free T4) suggests the patient is biochemically hyperthyroid or on the edge of hyperthyroidism, making continued treatment essential. 1

Optimal Dosing Strategy During Pregnancy

The treatment goal is to maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest possible thioamide dosage. 1

• This approach minimizes fetal exposure to methimazole while preventing maternal hyperthyroidism. 1

• Measure free T4 or FTI every 2-4 weeks and adjust the methimazole dose accordingly. 1

• TSH will remain suppressed during pregnancy in Graves' disease and should not be used as the primary monitoring parameter—free T4 is the critical value. 1

Monitoring for Fetal Thyroid Suppression

Although suppression of fetal and neonatal thyroid function can occur with thioamide therapy for Graves' disease, it is usually transient and treatment is rarely required. 1

• Women with Graves' disease should be monitored for normal heart rate and appropriate fetal growth; unless problems are detected, ultrasound screening for fetal goiter is not necessary. 1

• The newborn's physician must be informed that the mother has Graves' disease because of the associated risk of neonatal thyroid dysfunction. 1

Alternative Considerations (Propylthiouracil)

• Some guidelines suggest propylthiouracil (PTU) may be preferable in the first trimester due to the risk of methimazole-associated congenital malformations, with a switch to methimazole in the second and third trimesters to avoid PTU-associated hepatotoxicity. 2, 5

• However, recent studies found no significant differences between propylthiouracil and methimazole in mean free T4 or TSH levels in newborn cord-blood samples, as well as no cases of aplasia cutis and similar rates of fetal anomalies for both agents. 1

• If the patient is already tolerating methimazole well in early first trimester, continuing at the lowest effective dose is reasonable. 1

Critical Pitfalls to Avoid

• Never stop antithyroid medication abruptly in a pregnant woman with elevated TRAb without a plan for alternative management, as this risks thyroid storm and maternal heart failure. 1

• Do not aim for normal TSH during pregnancy—TSH will be suppressed by both the disease and by hCG stimulation of the thyroid; free T4 is the appropriate monitoring parameter. 1

• Avoid excessive methimazole dosing that could cause fetal hypothyroidism and goiter—use the minimum dose to keep free T4 in the high-normal range. 1, 2

• Do not use radioactive iodine (I-131) during pregnancy, as it is absolutely contraindicated and can cause fetal thyroid ablation if exposure occurs after 10 weeks of gestation. 1

Disease Course During Pregnancy

• In many pregnant women with Graves' disease, thyroid dysfunction diminishes as pregnancy progresses; consequently, a reduction of methimazole dosage may be possible, and in some instances, antithyroid therapy can be discontinued several weeks or months before delivery. 2

• This natural improvement occurs because TRAb levels often decline during pregnancy. 2

Breastfeeding Considerations

• Women treated with methimazole can breastfeed safely, as several long-term studies found no effect on clinical status in nursing infants of mothers taking methimazole. 1, 2