Methimazole Dosing in Second Trimester of Pregnancy
Methimazole is the preferred antithyroid drug in the second trimester of pregnancy, with dosing typically ranging from 5-40 mg daily depending on disease severity, using the lowest dose necessary to maintain free T4 in the high-normal range. 1, 2
Medication Selection in Second Trimester
Switch from propylthiouracil (PTU) to methimazole after the first trimester is complete to reduce the risk of PTU-associated hepatotoxicity while avoiding the critical period of methimazole-associated congenital malformations (which occur primarily in the first trimester). 1, 2, 3
Methimazole is preferred over PTU in the second and third trimesters because PTU carries approximately a 0.1% risk of severe hepatotoxicity in adults, with increasing case reports of severe liver injury. 3, 4
The teratogenic concerns with methimazole (choanal atresia, esophageal atresia, omphalocele) are primarily first-trimester exposures; by the second trimester, organogenesis is complete and these risks are no longer relevant. 3, 4
Specific Dosing Recommendations
Initial dosing should be based on hyperthyroidism severity: 5
- Mild hyperthyroidism: 15 mg daily divided into 3 doses at 8-hour intervals
- Moderately severe hyperthyroidism: 30-40 mg daily divided into 3 doses at 8-hour intervals
- Severe hyperthyroidism: 60 mg daily divided into 3 doses at 8-hour intervals
Maintenance dosing: 5-15 mg daily once thyroid function is controlled. 5
Treatment Goals and Monitoring
The therapeutic target is to maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest possible methimazole dose. 1, 2
Monitor free T4 or FTI every 2-4 weeks to guide dosage adjustments throughout the second trimester. 1, 2
Check TSH every trimester, though free T4/FTI is the primary monitoring parameter for dose titration. 1
Critical Safety Considerations
Untreated hyperthyroidism poses greater risks than methimazole treatment in the second trimester, including preeclampsia, preterm delivery, heart failure, miscarriage, low birth weight, and stillbirth. 1, 2
Monitor for agranulocytosis (presenting with sore throat and fever), hepatitis, vasculitis, and thrombocytopenia as potential side effects. 1, 2
Beta-blockers such as propranolol can be used temporarily to control symptoms (tremors, palpitations) while waiting for methimazole to achieve therapeutic effect. 1, 2
Common Pitfalls to Avoid
Do not continue PTU throughout pregnancy when the patient could be switched to methimazole after the first trimester, as this unnecessarily exposes the mother to ongoing hepatotoxicity risk. 2, 3
Do not over-treat by using higher doses than necessary; the goal is the lowest dose that maintains high-normal free T4, not complete normalization of TSH. 1, 2
Radioactive iodine remains absolutely contraindicated throughout all of pregnancy. 1, 2
Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction from transplacental passage of thyroid-stimulating antibodies. 1