PTU in Pregnancy
Propylthiouracil (PTU) should be used as first-line therapy for hyperthyroidism during the first trimester of pregnancy, then switched to methimazole for the second and third trimesters to minimize both teratogenic and hepatotoxic risks. 1, 2
First Trimester Management
PTU is the preferred antithyroid drug during the first trimester because methimazole carries a higher risk of specific congenital anomalies including choanal atresia, aplasia cutis congenita, and esophageal atresia. 2, 3, 4
The teratogenic pattern associated with methimazole exposure in early pregnancy is well-documented, though the absolute risk remains relatively low. 5, 6
PTU should be continued throughout the first trimester to maintain maternal euthyroidism, as untreated hyperthyroidism itself increases the risk of adverse pregnancy outcomes. 7
Second and Third Trimester Management
Switch from PTU to methimazole after the first trimester (typically around 12-16 weeks gestation) because PTU carries a significant risk of severe hepatotoxicity that can lead to liver failure, transplantation, or maternal death. 1, 2, 3
The hepatotoxic risk of PTU is particularly concerning with prolonged use, making it unsuitable for continued therapy beyond the first trimester. 8, 6
Methimazole is safer than PTU in the second and third trimesters, as the critical period for methimazole-associated birth defects has passed. 1, 7
Practical Switching Protocol
Directly substitute PTU for methimazole at the beginning of the second trimester using an approximate 10:1 conversion ratio (e.g., 100 mg PTU ≈ 10 mg methimazole), with individual titration based on thyroid function. 1, 8
Monitor thyroid function tests every 4-6 weeks during the switch and dose adjustment period. 8
Target free thyroxine (T4) levels in the upper one-third of the trimester-specific reference range to ensure adequate maternal thyroid control. 7
Critical Safety Monitoring
Monitor for PTU hepatotoxicity during first trimester use by educating patients about symptoms of liver dysfunction (jaundice, dark urine, abdominal pain, nausea). 2, 8
Monitor for agranulocytosis with both drugs (affects 3 per 10,000 patients) by educating patients to immediately discontinue medication and seek care for fever, sore throat, or signs of infection. 2, 8
Regular liver function testing is essential when using PTU, though severe hepatotoxicity can occur suddenly even with normal baseline tests. 8, 6
Evidence Strength and Nuances
Meta-analysis data confirm that PTU has a lower risk of congenital anomalies compared to methimazole (OR 0.80,95% CI 0.69-0.92, P=0.002). 4
The evidence for switching between drugs during pregnancy versus using PTU alone throughout pregnancy remains unclear, as studies have not definitively shown that switching reduces overall birth defect risk. 4, 6
Despite this uncertainty, the current standard of care favors switching to avoid prolonged PTU-associated hepatotoxicity risk, which can be catastrophic in pregnancy. 6
Common Pitfalls to Avoid
Do not use methimazole in the first trimester unless PTU is contraindicated or unavailable, as the teratogenic risk is highest during organogenesis. 2, 3
Do not continue PTU beyond the first trimester when methimazole can be safely used, as this unnecessarily exposes the mother to cumulative hepatotoxicity risk. 8, 6
Do not undertreated maternal hyperthyroidism out of fear of medication risks, as uncontrolled hyperthyroidism itself increases the risk of congenital anomalies, preterm birth, and other adverse outcomes. 5, 7
Ensure effective contraception is used before conception in women with hyperthyroidism, as both drugs normalize ovulatory function and increase unplanned pregnancy risk. 2