What are the recommendations for antithyroid medication (specifically propylthiouracil (PTU) and methimazole (MMI)) use in pregnant women?

Management of Antithyroid Drugs in Pregnancy

Propylthiouracil (PTU) should be used during the first trimester of pregnancy, followed by a switch to methimazole (MMI) for the second and third trimesters to minimize both the risk of methimazole-associated birth defects and PTU-associated hepatotoxicity. 1

Medication Selection by Trimester

First Trimester

• Use propylthiouracil (PTU) due to lower risk of congenital malformations
• MMI/carbimazole is associated with rare but specific congenital defects when used in first trimester, including:
  • Aplasia cutis
  • Craniofacial malformations (facial dysmorphism, choanal atresia)
  • Gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula)
  • Omphalocele 2

Second and Third Trimesters

• Switch from PTU to methimazole after first trimester 1, 2
• This switch is recommended because:
  • PTU carries a higher risk of severe hepatotoxicity
  • The teratogenic risk of MMI is no longer relevant after the first trimester
  • MMI has a longer half-life allowing for once-daily dosing 1

Dosing and Monitoring

Dosing Guidelines

• Initial MMI dose: 0.4 mg/kg body weight daily, divided into 3 doses given at 8-hour intervals 1
• Maintenance MMI dose: 5-15 mg daily (approximately half of the initial dose) 1
• Goal: Maintain free T4 or Free T4 Index in the high-normal range using the lowest possible dose 1

Monitoring Schedule

• Monitor thyroid function every 2-4 weeks initially until stable 1
• Once stable, monitor every 3-6 months 1
• Measure free T4 or FTI every 2-4 weeks to adjust dosing appropriately 1
• Monitor prothrombin time before surgical procedures due to potential hypoprothrombinemia with both medications 3, 2

Important Safety Considerations

Maternal Risks

• PTU risks:
  • Severe hepatotoxicity (potentially fatal) 3
  • Agranulocytosis, vasculitis, thrombocytopenia 3
• MMI risks:
  • Agranulocytosis (potentially life-threatening) 2
  • Vasculitis (can cause severe complications including kidney injury, alveolar hemorrhage) 2
  • Less hepatotoxicity compared to PTU 2

Fetal Considerations

• Both medications cross the placenta and can cause fetal goiter and hypothyroidism 3, 2
• Untreated or inadequately treated maternal hyperthyroidism increases risk of:
  • Maternal heart failure
  • Spontaneous abortion
  • Preterm birth
  • Stillbirth
  • Fetal or neonatal hyperthyroidism 3, 2

Dose Adjustments During Pregnancy

• Thyroid dysfunction often improves as pregnancy progresses 1
• Dose reduction may be possible later in pregnancy 1
• In some cases, antithyroid therapy can be discontinued several weeks or months before delivery 3, 2

Contraindications and Precautions

• Radioactive iodine (I-131) treatment is absolutely contraindicated during pregnancy 1
• Beta blockers (e.g., propranolol) can be used temporarily to control symptoms until antithyroid drugs reduce thyroid hormone levels 1

Breastfeeding Considerations

• Both MMI and PTU are present in breast milk in small amounts 3, 2
• Women treated with either medication can safely breastfeed 1, 2
• Monitor infant thyroid function at frequent (weekly or biweekly) intervals when mother is breastfeeding while on antithyroid medication 1, 2

Patient Education and Monitoring

• Instruct patients to immediately report symptoms of:
  • Agranulocytosis (fever, sore throat) 2
  • Hepatotoxicity (fatigue, nausea, anorexia, right upper quadrant pain) 2
  • Vasculitis (new rash, hematuria, decreased urine output, dyspnea) 2
• Inform the newborn's physician of maternal hyperthyroidism treatment 1

This approach of using PTU in the first trimester followed by MMI for the remainder of pregnancy represents the safest management strategy for hyperthyroidism during pregnancy, balancing the risks of both medications to minimize harm to both mother and fetus.