In a pregnant patient in the second trimester taking methimazole 5 mg twice daily with a high free thyroxine (18.1 pmol/L) and a suppressed thyrotropin (<0.005 mIU/L), how should the antithyroid drug dose be adjusted?

Dose Adjustment for Methimazole in Second Trimester Hyperthyroidism

Reduce the methimazole dose immediately, as the current free T4 of 18.1 pmol/L is already in the high-normal range and the suppressed TSH indicates adequate thyroid suppression; the goal is to maintain free T4 in the high-normal range using the lowest effective dose to avoid fetal thyroid suppression. 1

Current Clinical Assessment

Your patient's thyroid function demonstrates:

• Free T4 at 18.1 pmol/L – likely already at or near the high-normal target range 1
• TSH <0.005 mIU/L – appropriately suppressed, indicating effective maternal thyroid control 1
• Current dose: methimazole 5 mg twice daily (10 mg/day total) – this is the correct medication for second trimester 1, 2

Therapeutic Target in Second Trimester

• Maintain free T4 in the high-normal range (not mid-normal or low-normal) using the minimum effective methimazole dose; this creates a mildly hyperthyroid maternal state that prevents fetal thyroid suppression while controlling maternal disease 1, 3
• Avoid over-treatment: Excessive dosing that drives free T4 to mid-normal or low-normal levels can cause fetal hypothyroidism and goiter 1, 4

Recommended Dose Adjustment

• Decrease methimazole to 2.5–5 mg daily (reduce by approximately 50% from current 10 mg/day) since the free T4 is already at target and further suppression risks fetal thyroid dysfunction 1, 3
• The lowest dose that maintains high-normal free T4 is optimal to minimize drug exposure while preserving maternal control 1, 3

Monitoring Schedule

• Recheck free T4 (or FTI) in 2–4 weeks after any dose adjustment to ensure the target range is maintained 1, 2, 3
• Continue monitoring free T4 every 2–4 weeks throughout the second and third trimesters, as thyroid dysfunction often diminishes as pregnancy progresses and further dose reductions may become possible 1, 4
• Check TSH each trimester once stable control is achieved 1

Safety Monitoring

Agranulocytosis

• Instruct the patient to report sore throat or fever immediately, as these may signal agranulocytosis; obtain a complete blood count urgently and discontinue methimazole if confirmed 1, 4

Hepatotoxicity

• Monitor for symptoms of liver dysfunction (anorexia, pruritus, right upper quadrant pain); although methimazole carries lower hepatotoxicity risk than propylthiouracil, cases of acute liver failure have occurred 4
• Discontinue methimazole promptly if hepatic transaminases exceed 3 times the upper limit of normal 4

Vasculitis

• Watch for new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, which may indicate ANCA-positive vasculitis; discontinue methimazole and initiate appropriate intervention if vasculitis is suspected 4

Fetal and Neonatal Considerations

• Transient fetal or neonatal thyroid suppression may occur with thioamide therapy but is usually self-limited and rarely requires treatment 1, 3
• Inform the newborn's physician about maternal Graves' disease to arrange appropriate neonatal thyroid monitoring 1, 2, 3

Adjunctive Symptom Management

• Beta-blockers (e.g., propranolol) can be used temporarily to control tremor, palpitations, and tachycardia if maternal symptoms persist, but should be discontinued once biochemical control is achieved 1, 2

Common Pitfalls to Avoid

• Do not target mid-normal or low-normal free T4 levels – this increases the risk of fetal hypothyroidism and goiter; the high-normal range is intentional 1
• Do not continue the current dose without reassessment – the suppressed TSH and high-normal free T4 indicate the dose may already be excessive for ongoing therapy 1
• Do not switch back to propylthiouracil in the second trimester – methimazole is preferred after the first trimester due to lower risk of maternal hepatotoxicity 1, 2, 5, 6

Postpartum Planning

• Breastfeeding is safe with methimazole at doses up to 5 mg (and likely higher doses as well), as only minimal drug enters breast milk 1, 3, 4
• Recheck thyroid function 1–2 weeks postpartum and adjust dosing as needed, since thyroid hormone requirements often change after delivery 1