Can Methimazole Be Used in Pregnant Patients?
Methimazole can be used in pregnant patients, but propylthiouracil (PTU) is the preferred antithyroid drug during the first trimester due to methimazole's association with rare but specific congenital malformations; after the first trimester, switching to methimazole is recommended to minimize maternal hepatotoxicity risk. 1, 2
First Trimester: Propylthiouracil Is Preferred
Use PTU exclusively during the first trimester to avoid methimazole-associated birth defects, which include choanal atresia, esophageal atresia, and aplasia cutis congenita. 1, 3, 4
Methimazole exposure during organogenesis (first trimester) carries a higher risk of congenital anomalies compared to PTU (OR 0.80,95% CI 0.69–0.92, P = 0.002). 4
The FDA classifies methimazole as Pregnancy Category D, warning that it crosses the placenta and can induce goiter, cretinism, and rare malformations in the developing fetus. 5
Second and Third Trimesters: Switch to Methimazole
After the first trimester, switch from PTU to methimazole to reduce the risk of maternal hepatotoxicity, which is a rare but severe complication of PTU therapy. 1, 2, 6
PTU has been associated with fulminant hepatic failure requiring liver transplantation and death, prompting the FDA to issue a black box warning. 3, 7
Methimazole is safer for the mother after organogenesis is complete, and the teratogenic risk is confined to the first trimester. 1, 6
Treatment Goals and Monitoring
Maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest effective thioamide dose to avoid fetal thyroid suppression while controlling maternal hyperthyroidism. 1, 2
Check free T4 or FTI every 2–4 weeks during pregnancy to guide dose adjustments. 1, 2
Once stable, check TSH every trimester. 1
The goal is to maintain a mildly hyperthyroid maternal state rather than full euthyroidism, as excessive dosing can suppress the fetal thyroid. 1
Safety Monitoring for Both Drugs
Agranulocytosis
- Monitor for sore throat and fever, which may signal agranulocytosis; obtain an immediate complete blood count and discontinue the thioamide if confirmed. 1, 2
Hepatotoxicity (PTU-Specific)
Severe liver injury has been reported with PTU, particularly at doses ≥300 mg/day, but cases occur even at 50 mg/day. 1
This risk is the primary reason to switch to methimazole after the first trimester. 1, 6
Other Adverse Effects
- Clinicians should remain vigilant for vasculitis and thrombocytopenia as possible thioamide-related toxicities. 1
Fetal and Neonatal Considerations
Transient fetal or neonatal thyroid suppression may occur with either drug but rarely requires treatment. 1
Notify the newborn's physician about maternal Graves' disease so appropriate neonatal thyroid monitoring can be arranged. 1, 2
Monitor fetal heart rate and growth in women with Graves' disease. 1
Breastfeeding Guidance
Both PTU and methimazole are compatible with breastfeeding, as only minimal drug amounts enter breast milk. 1, 5, 8
A long-term study of 139 thyrotoxic lactating mothers and their infants found no toxicity in nursing infants whose mothers received methimazole. 5
Monitor thyroid function in the infant at frequent (weekly or biweekly) intervals if the mother is breastfeeding while on antithyroid drugs. 5
Risks of Inadequate Treatment
Untreated or inadequately treated hyperthyroidism increases risks of severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight. 1, 2, 6
In pregnant women with untreated or inadequately treated Graves' disease, there is an increased risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal or neonatal hyperthyroidism. 5
Switching Strategy: Is It Better Than PTU Alone?
Switching between PTU and methimazole during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00–1.40, P = 0.061). 4
However, the switch is still recommended after the first trimester to minimize maternal hepatotoxicity risk, which is a serious concern with prolonged PTU use. 1, 6
The evidence for switching is based on balancing fetal teratogenic risk (first trimester) against maternal hepatotoxic risk (second and third trimesters). 1, 3
Thyroid Storm Management
Thyroid storm is a medical emergency requiring immediate treatment with PTU or methimazole, potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care without waiting for laboratory confirmation. 1, 2
Avoid delivery during thyroid storm unless absolutely necessary, as the crisis poses high risk to both mother and fetus. 1, 2
When Surgery Is Indicated
Thyroidectomy is reserved for women who do not respond to thioamide therapy or develop severe drug intolerance (agranulocytosis, severe hepatotoxicity). 1, 2
If surgery is necessary, perform during the second trimester to minimize fetal risk. 1, 2
Absolute Contraindication: Radioactive Iodine
Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation. 1, 2
Women must wait four months after I-131 treatment before breastfeeding. 1, 2
Common Pitfalls to Avoid
Failing to switch from PTU to methimazole after the first trimester increases the risk of maternal hepatotoxicity. 1
Using methimazole during the first trimester increases the risk of congenital malformations, particularly choanal atresia and aplasia cutis congenita. 3, 4
Over-treating maternal hyperthyroidism can lead to fetal hypothyroidism; maintain free T4 in the high-normal range, not mid-normal. 1
Ignoring symptoms of agranulocytosis (sore throat, fever) can lead to life-threatening infection; obtain CBC immediately and discontinue the drug. 1, 2