Methimazole vs PTU in Hyperthyroidism
Methimazole is the preferred first-line antithyroid drug for hyperthyroidism due to superior efficacy and safety profile, with the critical exception of the first trimester of pregnancy when propylthiouracil (PTU) must be used. 1
Drug Selection Algorithm
Non-Pregnant Patients
- Methimazole is the drug of choice for all non-pregnant patients with hyperthyroidism 1
- PTU is reserved exclusively for patients who are intolerant to methimazole 2
- PTU carries a black box warning for severe liver injury and acute liver failure, including cases requiring liver transplantation in both adults and children 2
Pregnant Patients
- First trimester (weeks 0-13): PTU is mandatory due to methimazole's association with congenital malformations including aplasia cutis and choanal/esophageal atresia 1, 3, 4
- Meta-analysis confirms PTU has lower risk of congenital anomalies compared to MMI (OR 0.80,95%CI 0.69-0.92) 5
- Second and third trimesters: Switch to methimazole to avoid PTU's hepatotoxicity risk 3
- Goal is maintaining free T4 in the high-normal range using the lowest possible dose 1, 6
Pediatric Patients
- Methimazole is strongly preferred in children due to postmarketing reports of severe liver injury with PTU 3
Safety Profile Comparison
Hepatotoxicity
- PTU causes significantly more liver injury than methimazole (OR 2.40,95%CI 1.16-4.96) 7
- PTU elevates transaminases much more frequently (OR 3.96,95%CI 2.49-6.28) 7
- PTU hepatotoxicity can be fatal and may require liver transplantation 2
Other Adverse Effects
- No significant difference in agranulocytosis, rash, or urticaria between the two drugs 7
- Both drugs require monitoring for agranulocytosis (typically within first 3 months), presenting as sore throat and fever requiring immediate CBC and drug discontinuation 1
Birth Defects
- Methimazole has higher odds of birth defects in first trimester (OR 1.29,95%CI 1.09-1.53) 7
- Switching between MMI and PTU during pregnancy does not reduce birth defect risk compared to PTU alone 5
Dosing and Administration
Methimazole
- Starting dose: 10-30 mg as single daily dose 4
- Can be administered once daily (major advantage over PTU) 4
- Less expensive and more widely available 4
PTU
- Starting dose: 100-300 mg every 6 hours (requires multiple daily doses) 4
- More frequent dosing reduces compliance 4
Monitoring Strategy
- Monitor free T4 or free T3 index every 2-4 weeks during initial treatment 1
- Critical pitfall: Target is high-normal free T4/T3, NOT normalized TSH (which may remain suppressed for months) 1
- Do not reduce dose based solely on suppressed TSH while free T4 remains elevated 1
Breastfeeding
- Both methimazole and PTU are compatible with breastfeeding 6, 3
- No contraindications for either drug during lactation 4
Common Clinical Pitfall
The most dangerous error is using methimazole in the first trimester of pregnancy or continuing PTU beyond the first trimester when methimazole would be safer. Always verify pregnancy status before initiating methimazole and switch to methimazole after week 13 of gestation. 3, 2