Methimazole During Pregnancy

Direct Answer

Methimazole should be avoided during the first trimester of pregnancy due to its association with rare but specific congenital malformations; propylthiouracil (PTU) is the preferred antithyroid drug during this period, with a switch to methimazole recommended for the second and third trimesters. 1, 2, 3

Treatment Algorithm by Trimester

First Trimester (Weeks 1-13)

Use propylthiouracil (PTU) as first-line therapy during organogenesis to minimize teratogenic risk 1, 2, 3
PTU is preferred because methimazole exposure during the first trimester has been linked to congenital defects including:
- Aplasia cutis (scalp defects) 3
- Choanal atresia (nasal passage blockage) 3, 4
- Esophageal atresia with or without tracheoesophageal fistula 3, 4
- Omphalocele (abdominal wall defects) 3
- Facial dysmorphism 3

Second and Third Trimesters (Weeks 14-40)

Switch from PTU to methimazole after the first trimester 1, 3, 5
This switch is recommended because PTU carries a risk of severe hepatotoxicity (approximately 0.1% of exposed adults), including acute liver failure that can be catastrophic during pregnancy 3, 5, 6
Methimazole is preferred in later pregnancy due to better safety profile for maternal liver function 5, 7

Critical Monitoring Requirements

Thyroid Function Monitoring

Measure free T4 or Free Thyroxine Index (FTI) every 2-4 weeks to adjust dosing 8, 1, 2
Goal: maintain free T4 or FTI in the high-normal range using the lowest possible dose 8, 1
Check TSH level every trimester once stable 8, 1

Maternal Safety Monitoring

Monitor for agranulocytosis: Instruct patients to immediately report fever or sore throat 8, 3
If agranulocytosis suspected, obtain complete blood count and discontinue the drug immediately 8, 2
Monitor for hepatotoxicity (particularly with PTU): Watch for anorexia, pruritus, right upper quadrant pain 3
Discontinue drug if hepatic transaminases exceed 3 times upper limit of normal 3

Fetal Monitoring

Monitor fetal heart rate and growth for appropriate development 8, 2
Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 8, 1, 2
Fetal thyroid suppression from thioamide therapy is usually transient and rarely requires treatment 8, 2

Dosing Principles

Use the lowest effective dose to maintain maternal euthyroidism while minimizing fetal exposure 3
If methimazole must be used in first trimester (e.g., PTU intolerance), use lowest possible dose and counsel patient about potential fetal risks 3
Beta-blockers (e.g., propranolol) can temporarily manage symptoms until thioamide therapy reduces thyroid hormone levels 8, 1, 2

Absolute Contraindications

Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 8, 1, 2
If inadvertent I-131 exposure occurs after 10 weeks gestation, counsel about risk of congenital hypothyroidism and discuss pregnancy continuation 8

Risks of Untreated Hyperthyroidism

Inadequately treated maternal hyperthyroidism carries significant risks that often outweigh medication risks:

Maternal Complications

Preeclampsia 8
Heart failure 1, 2, 3
Preterm delivery 1

Fetal/Neonatal Complications

Spontaneous abortion 2, 3
Stillbirth 1, 2, 3
Low birth weight 8
Fetal or neonatal hyperthyroidism 2, 3

When Surgery Is Indicated

Reserve thyroidectomy for women who do not respond to thioamide therapy 8, 1, 2
If surgery is necessary, second trimester is the preferred timing 1
Consider surgery if patient develops severe drug intolerance (agranulocytosis, severe hepatotoxicity) 1

Breastfeeding Considerations

Both PTU and methimazole are present in breast milk but breastfeeding is considered safe with either medication 8, 3
Monitor infant thyroid function at frequent (weekly or biweekly) intervals during lactation 3
Long-term studies of 139 thyrotoxic lactating mothers found no toxicity in nursing infants 3

Key Clinical Pitfalls to Avoid

Do not continue methimazole through first trimester if pregnancy is planned or discovered early—switch to PTU immediately 1, 2, 3
Do not keep patients on PTU throughout entire pregnancy—the hepatotoxicity risk increases with duration of exposure 5, 6
Do not use excessive doses—fetal goiter and cretinism can result from overtreatment 8, 3
Do not ignore symptoms of agranulocytosis or hepatotoxicity—these are medical emergencies requiring immediate drug discontinuation 8, 3

Is methimazole (antithyroid medication) safe to use during pregnancy?

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