What is the preferred antithyroid drug, its initial dosage, and monitoring plan for a 36‑year‑old non‑pregnant woman with newly diagnosed biochemical hyperthyroidism characterized by elevated triiodothyronine, elevated free thyroxine, and suppressed thyroid‑stimulating hormone?

Preferred Antithyroid Drug and Management for Newly Diagnosed Hyperthyroidism

For a 36-year-old non-pregnant woman with newly diagnosed overt hyperthyroidism (T3 400, T4 16, TSH <0.005), methimazole is the preferred antithyroid drug, started at 15-20 mg daily, with monitoring of thyroid function tests every 4-6 weeks until euthyroid, then every 2-3 months. 1, 2

Rationale for Methimazole as First-Line

• Methimazole is the preferred antithyroid drug for non-pregnant adults because it has a longer half-life allowing once-daily dosing, fewer side effects, and better patient adherence compared to propylthiouracil 1, 2
• Propylthiouracil is specifically reserved for the first trimester of pregnancy due to methimazole's potential teratogenic effects (aplasia cutis, esophageal/choanal atresia), but your patient is explicitly non-pregnant 3, 4, 5
• In non-pregnant patients, methimazole has a superior safety profile with lower rates of hepatotoxicity compared to propylthiouracil's risk of severe liver injury 3

Initial Dosing Strategy

• Start methimazole at 15-20 mg once daily for overt hyperthyroidism with markedly elevated thyroid hormones like your patient's presentation 1, 2
• The dose correlates with disease severity—with T3 of 400 and T4 of 16 (both significantly elevated), this patient requires the higher end of the initial dosing range 2
• Once-daily dosing improves adherence and is equally effective as divided doses 1

Monitoring Protocol

Initial Phase (First 3 Months)

• Recheck free T4, free T3, and TSH every 4-6 weeks until thyroid hormone levels normalize 2, 6
• TSH will remain suppressed for months even after thyroid hormones normalize, so use free T4 and free T3 as primary markers of treatment response initially 6
• Monitor complete blood count (CBC) and liver function tests at baseline and if symptoms of agranulocytosis (fever, sore throat) or hepatotoxicity develop 1, 2

Maintenance Phase (After Achieving Euthyroid State)

• Once free T4 and T3 normalize, reduce monitoring frequency to every 2-3 months 2, 6
• Adjust methimazole dose in 5-10 mg increments based on thyroid function tests, targeting free T4 and T3 in the normal range 1, 2
• Continue treatment for 12-18 months before considering discontinuation, as this duration maximizes remission rates in Graves' disease 1, 2

Critical Safety Monitoring

• Warn the patient to stop methimazole immediately and seek urgent medical attention if she develops fever, sore throat, mouth ulcers, or jaundice—these indicate potentially life-threatening agranulocytosis or hepatotoxicity 1, 2
• Agranulocytosis occurs in 0.2-0.5% of patients, typically within the first 3 months of therapy 2
• Routine CBC monitoring does not prevent agranulocytosis because it develops rapidly, so patient education about warning symptoms is more critical than scheduled blood tests 2

Determining the Underlying Cause

• Measure TSH-receptor antibodies (TRAb) to confirm Graves' disease as the etiology, which is the most common cause in this age group 1, 2
• If TRAb is negative or thyroid nodules are palpable, obtain thyroid ultrasound and consider radioiodine uptake scan to distinguish toxic nodular goiter from Graves' disease 1, 2
• The underlying cause determines long-term management: Graves' disease may remit after 12-18 months of antithyroid drugs, whereas toxic nodular goiter typically requires definitive therapy (radioactive iodine or surgery) 1, 2

Common Pitfalls to Avoid

• Do not use TSH as the primary marker of treatment response initially—it remains suppressed for months after thyroid hormones normalize and will mislead dose adjustments 6
• Do not switch to propylthiouracil unless methimazole causes severe side effects—propylthiouracil has higher hepatotoxicity risk and requires multiple daily doses 3, 1
• Do not delay treatment while awaiting antibody results—start methimazole immediately based on biochemical hyperthyroidism to prevent cardiac complications (atrial fibrillation, heart failure) and bone loss 2
• Avoid overtreatment causing iatrogenic hypothyroidism—this occurs in 14-21% of patients and increases cardiovascular and bone risks 7

Special Considerations for This Patient

• At 36 years old and non-pregnant, methimazole is unequivocally the correct choice over propylthiouracil 1, 2
• If she plans pregnancy in the future, switch to propylthiouracil before conception or as soon as pregnancy is confirmed, then switch back to methimazole after the first trimester 3, 4
• Untreated hyperthyroidism increases risks of miscarriage, preterm labor, low birth weight, and maternal heart failure if she becomes pregnant 4, 5