What is the drug of choice for hyperthyroidism (overactive thyroid) in the first trimester of pregnancy?

Drug of Choice for Hyperthyroidism in First Trimester Pregnancy

Propylthiouracil (PTU) is the drug of choice for treating hyperthyroidism during the first trimester of pregnancy. 1, 2

Rationale for PTU in First Trimester

• PTU is preferred over methimazole (MMI) during the first trimester due to the possible teratogenicity associated with MMI exposure during early pregnancy 1
• The FDA specifically states that "propylthiouracil may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy" 2
• While both medications are thioamides that inhibit thyroid peroxidase and reduce thyroid hormone production, their risk profiles differ significantly during pregnancy 1, 3

Treatment Algorithm for Hyperthyroidism in Pregnancy

1. First trimester: Use propylthiouracil (PTU) at the lowest effective dose 1
2. Second and third trimesters: Consider switching to methimazole to avoid PTU-associated hepatotoxicity 1, 3
3. Goal: Maintain free T4 or Free Thyroxine Index (FTI) in the high-normal range 1
4. Monitoring: Measure free T4 or FTI every 2-4 weeks to adjust dosage appropriately 1
5. Symptom management: Until thioamide therapy reduces thyroid hormone levels, a beta blocker (e.g., propranolol) can be used to reduce symptoms 1

Risks of Untreated Hyperthyroidism in Pregnancy

• Untreated or inadequately treated hyperthyroidism during pregnancy can lead to serious maternal and fetal complications 4:
  • Increased risk of maternal heart failure
  • Spontaneous abortion
  • Preterm birth
  • Stillbirth
  • Fetal or neonatal hyperthyroidism

Medication-Specific Risks

Propylthiouracil (PTU)

• Hepatotoxicity: PTU has been associated with rare but severe liver injury and acute liver failure 2
• Monitoring: Consider monitoring prothrombin time during therapy, especially before surgical procedures 2
• Other side effects: Agranulocytosis (presents with sore throat and fever), hepatitis, vasculitis, and thrombocytopenia 1

Methimazole (MMI)

• Teratogenicity: Associated with a specific pattern of rare congenital anomalies when used in first trimester 3, 5
• Potential birth defects: Choanal atresia, aplasia cutis congenita, and other facial, cardiac, and gastrointestinal abnormalities 5

Important Clinical Considerations

• Fetal and neonatal thyroid suppression can occur with thioamide therapy but is usually transient and rarely requires treatment 1
• Women with Graves' disease should be monitored for normal heart rate and appropriate fetal growth 1
• The newborn's physician should be informed about maternal Graves' disease due to the risk of neonatal thyroid dysfunction 1
• Radioactive iodine (I-131) treatment is absolutely contraindicated during pregnancy 1
• Thyroidectomy should be reserved only for women who do not respond to thioamide therapy 1

Warning Signs Requiring Immediate Attention

• If a patient on PTU develops signs of agranulocytosis (sore throat and fever), obtain a complete blood count and discontinue the medication 1
• For signs of hepatotoxicity (tiredness, nausea, anorexia, fever, pharyngitis, or malaise), discontinue PTU immediately and obtain liver function tests 2
• Thyroid storm is a medical emergency requiring immediate treatment with multiple medications including PTU or methimazole, iodide solutions, dexamethasone, and supportive care 1

By following these guidelines, the risks of both untreated hyperthyroidism and medication side effects can be minimized during pregnancy, optimizing outcomes for both mother and fetus.