What is the preferred treatment between propylthiouracil (PTU) and methimazole for a pregnant woman with hyperthyroidism?

PTU vs Methimazole in Pregnancy

Propylthiouracil (PTU) is the preferred antithyroid medication during the first trimester of pregnancy due to lower risk of congenital abnormalities, with consideration to switch to methimazole for the second and third trimesters. 1

First Trimester Management

• PTU is the drug of choice during the first trimester because methimazole is associated with specific congenital malformations including aplasia cutis (scalp defects) and choanal/esophageal atresia 2, 3
• The FDA explicitly states that "propylthiouracil may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy" 4
• A 2023 meta-analysis confirmed that pregnant women treated with methimazole had significantly higher risk of congenital anomalies compared to PTU (OR 0.80,95%CI 0.69-0.92, P = 0.002) 5
• The FDA drug label for methimazole warns that "due to the rare occurrence of congenital malformations associated with methimazole use, it may be appropriate to use an alternative anti-thyroid medication in pregnant women requiring treatment for hyperthyroidism particularly in the first trimester of pregnancy during organogenesis" 2

Second and Third Trimester Management

• Switch from PTU to methimazole for the second and third trimesters 1
• This recommendation balances the risk of PTU-associated severe hepatotoxicity (including cases requiring liver transplantation) against the teratogenic risk of methimazole, which is primarily limited to organogenesis in the first trimester 2, 4
• The FDA black box warning for PTU emphasizes that "severe liver injury and acute liver failure, in some cases fatal, have been reported in patients treated with propylthiouracil" 4

Treatment Goals and Monitoring

• Maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest possible dose 1
• Monitor thyroid function every 2-4 weeks to adjust medication dosage appropriately 1
• Check TSH level every trimester to ensure stable thyroid function 1
• Monitor for agranulocytosis (presenting with sore throat and fever) with both medications 1

Important Caveats

• Switching between medications during pregnancy (PTU to methimazole after first trimester) did not reduce the overall risk of birth defects compared to PTU alone in meta-analysis, though this strategy addresses the maternal hepatotoxicity risk 5
• Both medications have similar efficacy, with median time to normalization of free thyroxine index being 7 weeks for PTU and 8 weeks for methimazole (not statistically different) 6
• No statistically significant differences exist between PTU and methimazole regarding hepatotoxicity or miscarriage rates when analyzed across pregnancy 5
• In many pregnant women, thyroid dysfunction diminishes as pregnancy proceeds, allowing for dose reduction or discontinuation several weeks or months before delivery 2

Risks of Inadequate Treatment

• Untreated or inadequately treated hyperthyroidism increases risks of preeclampsia, preterm delivery, heart failure, miscarriage, stillbirth, and low birth weight 1
• Fetal and neonatal risks include thyroid dysfunction, requiring notification of the newborn's physician about maternal Graves' disease 1