How should methimazole be administered to a pregnant woman with hyperthyroidism (e.g., Graves disease), including timing, dosing, and monitoring?

Methimazole Administration in Pregnancy

Use propylthiouracil (PTU) exclusively during the first trimester, then switch to methimazole for the second and third trimesters to minimize both congenital malformations and maternal hepatotoxicity. 1

Trimester-Specific Medication Selection

First Trimester (Weeks 1-13)

• PTU is the preferred agent during organogenesis due to lower risk of congenital abnormalities compared to methimazole 2, 1
• Methimazole exposure in the first trimester has been associated with specific congenital malformations (choanal atresia, esophageal atresia, aplasia cutis) collectively termed "methimazole embryopathy" 3, 4
• The FDA labels methimazole as Pregnancy Category D, warning of potential fetal harm when used in the first trimester 3

Second and Third Trimesters (Weeks 14-40)

• Switch from PTU to methimazole after the first trimester is complete 1, 5
• This switch reduces the risk of PTU-associated maternal hepatotoxicity, which can be severe in the mother 1, 3
• Methimazole becomes the safer option after organogenesis is complete 2, 1

Dosing Strategy

Treatment Goals

• Maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest possible thioamide dosage 6, 1
• Use the minimum effective dose to control maternal hyperthyroidism while minimizing fetal thyroid suppression 6, 7
• Antithyroid drugs cross the placenta and can suppress fetal thyroid function more effectively than maternal thyroid function 7

Dose Adjustments

• Start with the lowest dose that achieves therapeutic effect 6
• As pregnancy progresses, thyroid dysfunction often diminishes, allowing dose reduction or even discontinuation several weeks before delivery 3

Monitoring Protocol

Frequency of Thyroid Function Testing

• Check free T4 or FTI every 2-4 weeks during active dose adjustment 6, 1
• Once stable and euthyroid, check TSH every trimester 6, 1
• A rising serum TSH indicates the need for a lower maintenance dose 3

Maternal Monitoring

• Monitor maternal heart rate and ensure it remains normal 6
• Watch for agranulocytosis: if sore throat and fever develop, obtain complete blood count immediately and discontinue the thioamide 6, 1
• Monitor for other side effects including hepatitis, vasculitis, and thrombocytopenia 6
• Check prothrombin time before surgical procedures, as methimazole may cause hypoprothrombinemia 3

Fetal Monitoring

• Monitor fetal heart rate and growth in women with Graves' disease 1
• Ultrasound screening for fetal goiter is not routinely necessary unless problems are detected 6
• Fetal thyroid suppression from thioamide therapy is usually transient and rarely requires treatment 6

Adjunctive Therapy

Symptomatic Management

• Beta-blockers (e.g., propranolol) can temporarily manage symptoms like tremors and palpitations until thioamide therapy reduces thyroid hormone levels 6, 1
• Use beta-blockers only as a bridge therapy, not as primary treatment 2
• Note that beta-blocker dosage may need reduction once the patient becomes euthyroid due to decreased clearance 3

Critical Contraindications and Warnings

Absolute Contraindications

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 6, 1
• Women must wait four months after I-131 treatment before breastfeeding 2, 1

When Surgery Is Indicated

• Thyroidectomy should be reserved only for women who do not respond to thioamide therapy or develop severe drug intolerance (agranulocytosis, marked hepatotoxicity) 6, 2, 1
• If surgery is necessary, perform during the second trimester to minimize fetal risk 2, 1
• Avoid thyroidectomy in pregnant women with active Graves' disease when possible, as withdrawal of antithyroid medication post-surgery combined with levothyroxine replacement creates high risk of isolated fetal hyperthyroidism 7

Risks of Inadequate Treatment

Maternal Complications

• Untreated or inadequately treated hyperthyroidism increases risks of severe preeclampsia, preterm delivery, heart failure, and miscarriage 6, 1, 3

Fetal/Neonatal Complications

• Low birth weight 6, 1
• Fetal thyrotoxicosis in women with history of Graves' disease 6
• Neonatal thyroid dysfunction (both hypothyroidism and hyperthyroidism possible due to transplacental antibodies) 6

Special Clinical Scenarios

Hyperemesis Gravidarum

• Biochemical hyperthyroidism associated with hyperemesis gravidarum rarely requires treatment unless other clinical signs of hyperthyroidism are present 2, 1

Thyroid Storm (Medical Emergency)

• Thyroid storm requires immediate treatment without waiting for laboratory confirmation 2, 1
• Treatment includes PTU or methimazole, potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care 2, 1
• Avoid delivery during thyroid storm unless absolutely necessary 2, 1

Postpartum Considerations

Breastfeeding

• Women treated with PTU or methimazole can safely breastfeed 6, 1
• Multiple studies found no adverse effects on nursing infants whose mothers received methimazole 3
• Monitor infant thyroid function at frequent (weekly or biweekly) intervals 3

Neonatal Follow-up

• Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 6, 1
• Monitor for postpartum thyroiditis in women with history of thyroid dysfunction 1

Key Pitfalls to Avoid

• Failing to switch from PTU to methimazole after the first trimester increases risk of maternal hepatotoxicity 1
• Over-aggressive antithyroid drug therapy can suppress fetal thyroid function more than maternal function 7
• Performing thyroidectomy during pregnancy in women with active Graves' disease may lead to isolated fetal hyperthyroidism 7
• Using radioactive iodine at any point during pregnancy causes irreversible fetal thyroid damage 6, 1