What antithyroid medications are safe for a pregnant woman with hyperthyroidism and how should they be managed across the trimesters?

Safe Antithyroid Drugs in Pregnancy

Use propylthiouracil (PTU) exclusively during the first trimester, then switch to methimazole for the second and third trimesters to minimize both congenital malformations and maternal hepatotoxicity. 1

First Trimester Management

• PTU is the preferred agent during the first trimester because methimazole exposure during organogenesis is associated with an increased risk of congenital malformations, including aplasia cutis, choanal atresia, and esophageal atresia. 2, 1

• PTU crosses the placenta minimally (only 0.025% enters breast milk) compared to methimazole, though this pharmacokinetic difference has not been definitively shown to reduce fetal thyroid suppression in clinical studies. 2, 3

• The FDA label confirms that methimazole may be associated with rare fetal abnormalities, making PTU the preferred first-trimester choice despite its hepatotoxicity risk. 4

Second and Third Trimester Management

• Switch from PTU to methimazole after the first trimester because continuing PTU beyond 12 weeks increases the risk of severe maternal hepatotoxicity, including fulminant liver failure requiring transplantation or resulting in death. 1, 4

• Methimazole up to 30 mg/day is considered safe in later pregnancy and is now the preferred agent for the remainder of gestation. 2, 5

• Failing to switch from PTU to methimazole after the first trimester unnecessarily exposes mothers to catastrophic liver injury, which can threaten both maternal and fetal survival. 1, 6

Treatment Goals Across All Trimesters

• Maintain maternal free T4 (or free thyroxine index) in the high-normal range or just above normal using the lowest effective thioamide dose—this mild hyperthyroid state prevents fetal thyroid suppression while controlling maternal disease. 2, 1

• Do not target mid-normal or low-normal free T4 levels, as this increases the risk of fetal hypothyroidism and goiter. 1

• Check free T4 (or FTI) every 2–4 weeks during active treatment to guide dose adjustments, and continue this monitoring throughout pregnancy. 2, 1

• Once TSH stabilizes, check it every trimester; a rising TSH indicates the need for dose reduction. 1, 5

Critical Safety Monitoring

Agranulocytosis (Both Drugs)

• Instruct patients to immediately report sore throat, fever, or signs of infection—these may signal agranulocytosis, which requires an immediate complete blood count and discontinuation of the thioamide if confirmed. 2, 1, 4

Hepatotoxicity (Primarily PTU)

• Severe liver injury with PTU has been reported at doses as low as 50 mg/day, though it is more common at doses ≥300 mg/day; patients should report tiredness, nausea, anorexia, or jaundice immediately. 1, 4

• PTU-induced liver disease can progress to fulminant hepatic failure in pregnancy, making the switch to methimazole after the first trimester essential. 6

Vasculitis and Other Toxicities

• Monitor for vasculitis (new rash, hematuria, decreased urine output, dyspnea, hemoptysis), hepatitis, and thrombocytopenia with both drugs. 2, 4

Adjunctive Symptom Management

• Use beta-blockers (e.g., propranolol) temporarily to control tremor, palpitations, and tachycardia until antithyroid therapy lowers thyroid hormone levels; discontinue once biochemical control is achieved. 1

• Beta-blocker doses may need reduction as the patient becomes euthyroid due to decreased clearance. 7, 4

Fetal and Neonatal Considerations

• Transient fetal or neonatal thyroid suppression may occur with thioamide therapy but is usually self-limited and rarely requires treatment. 1, 5

• Inform the newborn's physician about maternal Graves' disease because thyroid-stimulating antibodies cross the placenta and can cause neonatal thyrotoxicosis or immune-mediated thyroid dysfunction. 2, 1

• Monitor fetal heart rate and growth in women with Graves' disease throughout pregnancy. 1

Risks of Inadequate Treatment

• Untreated or inadequately treated hyperthyroidism increases the risk of severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight. 2, 1, 7

• These maternal and fetal complications justify aggressive treatment despite the risks of antithyroid drugs. 2

Surgical and Radioactive Iodine Considerations

• Thyroidectomy is reserved only for women who fail thioamide therapy or develop severe drug intolerance (agranulocytosis, marked hepatotoxicity); if necessary, perform surgery during the second trimester to minimize fetal risk. 2, 1

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy because it causes fetal thyroid ablation; women must wait at least four months after I-131 treatment before breastfeeding. 2, 1, 7, 4

Breastfeeding Guidance

• Both PTU and methimazole are compatible with breastfeeding—only minimal amounts enter breast milk, and multiple studies have found no adverse effects on nursing infants. 2, 1, 5, 7

• Methimazole (up to 30 mg/day) is now preferred over PTU during lactation due to severe hepatotoxicity concerns with PTU. 5

Common Pitfalls to Avoid

• Do not continue PTU beyond the first trimester—this is the single most important error to avoid, as it exposes mothers to preventable liver failure. 1

• Do not use radioactive iodine during pregnancy or within four months of planned breastfeeding—this will ablate the fetal thyroid. 2, 1

• Do not over-treat to achieve mid-normal free T4 levels—this causes fetal hypothyroidism; instead, maintain high-normal free T4. 2, 1

• Do not initiate antithyroid drugs during active labor unless thyroid storm is present—delivery should proceed without delay if the patient is biochemically controlled. 1