Switching from PTU to Methimazole During Pregnancy (≥13 weeks)
Switch from PTU 150 mg daily to methimazole 15 mg daily (using a 10:1 conversion ratio), then monitor free T4 or FTI every 2-4 weeks to adjust dosing and maintain free T4 in the high-normal range. 1
Rationale for Switching After First Trimester
- PTU is preferred only during the first trimester due to lower risk of congenital malformations (choanal atresia, esophageal atresia, omphalocele) associated with methimazole exposure during organogenesis 1, 2, 3, 4
- Methimazole becomes the preferred agent for the second and third trimesters because PTU carries a risk of severe hepatotoxicity (approximately 0.1% of exposed adults), which can progress to fulminant hepatic failure requiring transplantation 1, 4, 5, 6
- The switch at 13+ weeks gestation balances teratogenic risk (now minimal after organogenesis) against maternal hepatotoxicity risk 1, 3
Dosing Conversion
- Use a 10:1 conversion ratio: PTU 150 mg daily converts to methimazole 15 mg daily 3, 4
- Start methimazole at the calculated dose and discontinue PTU on the same day 1
- The goal is to use the lowest effective dose to maintain free T4 in the high-normal range, not mid-normal, to avoid fetal thyroid suppression 7, 1, 2
Monitoring Protocol
Initial Monitoring (First 4-8 Weeks After Switch)
- Check free T4 or free thyroxine index (FTI) every 2-4 weeks to guide dose adjustments 7, 1, 2
- Adjust methimazole dose based on free T4 levels, aiming for high-normal range 7, 1
- The therapeutic target is a subclinical hyperthyroid state during pregnancy, not full euthyroidism 7
Once Stable
- Continue checking free T4 or FTI every 2-4 weeks throughout pregnancy 1
- TSH can be checked each trimester once stable 1, 2
Safety Monitoring
- Monitor for agranulocytosis: Instruct patient to report sore throat, fever, or signs of infection immediately 7, 1, 2
- If these symptoms develop, obtain complete blood count immediately and discontinue methimazole if agranulocytosis confirmed 7, 1
- Monitor for other adverse effects including hepatitis, vasculitis, and thrombocytopenia 1
Fetal and Neonatal Considerations
- Monitor fetal heart rate and growth in women with Graves' disease throughout pregnancy 1, 2
- Transient fetal/neonatal thyroid suppression may occur with thioamide therapy but usually resolves without treatment 7, 1
- Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 7, 1, 2
Common Pitfalls to Avoid
- Do not fail to switch from PTU to methimazole after the first trimester, as this increases maternal hepatotoxicity risk 1
- Do not aim for mid-normal free T4 levels, as this may cause fetal hypothyroidism; target high-normal range instead 7, 1
- Do not use fixed dosing without monitoring, as this is associated with poor outcomes 1
- Do not delay switching if patient is already beyond first trimester, as PTU hepatotoxicity can occur at any time during treatment 4, 5, 6
Adjunctive Management
- Beta-blockers (e.g., propranolol) can temporarily manage symptoms like tremors and palpitations during the transition period until methimazole achieves therapeutic effect 7, 1, 2
- Discontinue beta-blockers once biochemical control is achieved 1
Postpartum Planning
- Breastfeeding is safe with methimazole at doses up to 20 mg daily 7, 1, 2
- Continue monitoring thyroid function postpartum with potential need for dose adjustment 7
- Monitor for postpartum thyroiditis in women with history of thyroid dysfunction 1
Evidence Quality Note
Both PTU and methimazole have been shown to be equally effective in normalizing thyroid function (median time 7-8 weeks), with similar rates of major congenital malformations when used appropriately by trimester 8. The recommendation to switch is based on the distinct safety profiles: methimazole's teratogenic risk is confined to first trimester organogenesis, while PTU's hepatotoxicity risk persists throughout treatment 3, 4, 5.