Which antithyroid drug is preferred during the first trimester of pregnancy and in a thyroid storm?

Propylthiouracil (PTU) is Preferred for Both First Trimester Pregnancy and Thyroid Storm

The answer is B. Propylthiouracil (PTU) is the preferred antithyroid drug during the first trimester of pregnancy and in thyroid storm management.

First Trimester Pregnancy

PTU should be used exclusively during the first trimester, then switched to methimazole for the second and third trimesters. 1

Rationale for PTU in First Trimester

• Methimazole carries a higher risk of congenital malformations when used in the first trimester, including a specific pattern of rare teratogenic effects such as choanal atresia, aplasia cutis congenita, and other facial, cardiac, gastrointestinal, and skin anomalies 2, 3
• Meta-analysis confirms PTU is safer: Pregnant women treated with methimazole had significantly higher risk of congenital anomalies compared to PTU (OR 0.80,95% CI 0.69-0.92, P=0.002) 4
• The American College of Obstetricians and Gynecologists explicitly recommends using PTU exclusively during the first trimester to minimize congenital malformations 1

Switch to Methimazole After First Trimester

• After the first trimester, switch to methimazole for the remainder of pregnancy to reduce maternal hepatotoxicity risk while the critical period for major organ formation has passed 1, 2
• PTU carries risk of severe hepatotoxicity, particularly at doses ≥300 mg/day, though cases occur even at 50 mg/day 1
• Failing to switch from PTU to methimazole after first trimester increases risk of maternal hepatotoxicity 1

Thyroid Storm Management

In thyroid storm, PTU is preferred over methimazole due to its additional mechanism of action.

Why PTU for Thyroid Storm

• PTU inhibits peripheral conversion of T4 to T3, making it particularly effective for the hypermetabolic crisis of thyroid storm 5
• Standard thyroid storm treatment includes PTU (or methimazole) plus potassium/sodium iodide solutions, dexamethasone, beta-blockers, and supportive care 6, 1, 5
• Treatment must begin immediately based on clinical suspicion without waiting for laboratory confirmation 5

Multi-Drug Protocol for Thyroid Storm

• Start PTU immediately as the first-line thionamide 5
• Administer iodide solutions at least 1 hour after starting PTU to prevent iodine from being used as substrate for new hormone synthesis 5
• Give dexamethasone to block peripheral T4 to T3 conversion and address potential relative adrenal insufficiency 5
• Use aggressive intravenous beta-blockers (propranolol or esmolol) to control tachycardia and peripheral thyroid hormone effects 5
• Provide supportive care: oxygen, antipyretics, appropriate monitoring 6

Pregnancy-Specific Considerations in Thyroid Storm

• Avoid delivery during thyroid storm unless absolutely necessary due to high maternal and fetal risk 6, 1, 5
• Thyroid storm presents with: fever, tachycardia disproportionate to fever, altered mental status (nervousness, restlessness, confusion, seizures), vomiting, diarrhea, and cardiac arrhythmia 6
• Untreated thyroid storm can result in: maternal heart failure, shock, stupor, coma, preeclampsia, preterm delivery, and miscarriage 6, 5

Why Not the Other Options

Methimazole (Option A)

• Contraindicated in first trimester due to higher teratogenic risk 1, 4
• Less effective in thyroid storm because it lacks PTU's ability to block peripheral T4 to T3 conversion 5

Atenolol (Option C)

• Beta-blockers are adjunctive only, used to control symptoms (tremor, palpitations, tachycardia) but do not treat the underlying thyroid hormone excess 7, 1
• Not an antithyroid drug and cannot be used as monotherapy

Lugol's Iodine (Option D)

• Iodine solutions are adjunctive, used to block thyroid hormone release but must be given at least 1 hour after starting a thionamide 5
• Cannot be used as monotherapy and may worsen hyperthyroidism if given before thionamide therapy

Critical Monitoring and Safety

• Monitor free T4 or FTI every 2-4 weeks to guide dose adjustments, targeting high-normal range with lowest effective dose 7, 1
• Watch for agranulocytosis: sore throat or fever requires immediate CBC and drug discontinuation if confirmed 7, 1
• Both PTU and methimazole are compatible with breastfeeding 1
• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 1, 5