What is the first-line recommended agent for a pregnant female in the first trimester with hyperthyroidism?

First-Line Agent for Hyperthyroidism in First Trimester Pregnancy

Propylthiouracil (PTU) is the preferred first-line agent for treating hyperthyroidism during the first trimester of pregnancy. 1, 2, 3

Rationale for PTU in First Trimester

The primary reason for choosing PTU over methimazole in early pregnancy is to avoid methimazole-associated congenital malformations. 4 Methimazole has been linked to rare but serious birth defects when used during organogenesis, including:

• Aplasia cutis (scalp defects) 4
• Choanal atresia (blocked nasal passages) 4, 5
• Esophageal atresia with or without tracheoesophageal fistula 4
• Omphalocele and omphalomesenteric duct abnormalities 4
• Facial dysmorphism 4

PTU crosses the placenta minimally (only 0.025% into breast milk) compared to methimazole, providing an additional safety margin. 2

Critical Timing: Switch to Methimazole After First Trimester

After the first trimester is complete, guidelines recommend switching from PTU to methimazole for the remainder of pregnancy. 1, 2, 6, 5 This switch is necessary because:

• PTU carries significant risk of severe hepatotoxicity, including acute liver failure requiring transplantation or resulting in death 3, 7
• The teratogenic risk of methimazole is confined to the first trimester during organogenesis 4
• Methimazole up to 30 mg/day is considered safe in the second and third trimesters 2

Treatment Goals and Monitoring

Maintain maternal free T4 (FT4) or free thyroxine index (FTI) in the high-normal range or just above normal using the lowest effective thioamide dose. 2 This approach:

• Prevents fetal hypothyroidism and goiter 3, 4
• Minimizes maternal complications
• Reduces drug exposure to the minimum necessary

Check FT4 or FTI every 2-4 weeks during active treatment until stable, then every 4 weeks once TSH is stable. 2

Essential Safety Monitoring

Instruct patients to immediately report fever, sore throat, or signs of infection, as these may indicate life-threatening agranulocytosis. 2, 3 Obtain complete blood count immediately if suspected. 3

Monitor for vasculitis by instructing patients to promptly report:

• New rash 2, 3
• Hematuria or decreased urine output 2, 3
• Dyspnea or hemoptysis 2, 3

Watch for hepatotoxicity signs including tiredness, nausea, anorexia, fever, pharyngitis, or malaise. 3 If these develop, discontinue PTU immediately and obtain liver function tests. 3

Contraindicated Treatments

Radioactive iodine (I-131) is absolutely contraindicated during pregnancy. 1, 2 If inadvertent exposure occurs:

• Before 10 weeks gestation: fetal thyroid unlikely to be ablated 1
• After 10 weeks: risk of congenital hypothyroidism; consider whether to continue pregnancy 1

Thyroidectomy should be reserved only for women who fail medical therapy, have large compressive goiters, or strongly prefer surgery, and should be performed during the second trimester when safest. 2

Common Pitfalls to Avoid

Do not continue PTU throughout the entire pregnancy - the hepatotoxicity risk makes this dangerous after the first trimester. 1, 5

Do not use methimazole in the first trimester unless PTU is contraindicated - the teratogenic window is precisely when organogenesis occurs. 4

Do not use excessive doses - the goal is control, not complete suppression, as overtreatment can cause fetal hypothyroidism and goiter. 2, 3

Do not delay treatment while awaiting test results in thyroid storm - this is a medical emergency requiring immediate intervention with PTU or methimazole plus supportive measures. 1, 2