What is the appropriate first‑line antithyroid medication and starting dose for an adult with overt hyperthyroidism (TSH 0.18 µIU/mL, free triiodothyronine 14.85 pg/mL, free thyroxine 20.65 ng/dL)?

Methimazole 30–40 mg Daily in Three Divided Doses

For an adult with overt hyperthyroidism presenting with TSH 0.18 µIU/mL, free T3 14.85 pg/mL (reference 4–7), and free T4 20.65 ng/dL (reference 10–20), initiate methimazole at 30–40 mg daily divided into three doses given at 8-hour intervals. This represents moderately severe hyperthyroidism based on the degree of thyroid hormone elevation, and the FDA-approved dosing for this severity is 30–40 mg daily 1.

Rationale for Methimazole as First-Line Therapy

• Antithyroid drugs, radioactive iodine ablation, and surgery are the three treatment options for overt hyperthyroidism, with treatment choices individualized based on patient factors, disease severity, and etiology 2.
• Methimazole is the preferred antithyroid drug in most clinical scenarios due to its once- or twice-daily dosing, lower risk of hepatotoxicity compared to propylthiouracil, and established efficacy 2.
• Overt hyperthyroidism is defined as suppressed TSH with elevated free T4 and/or T3, which this patient clearly demonstrates 2.

Dosing Strategy Based on Disease Severity

• The initial daily dosage is 15 mg for mild hyperthyroidism, 30–40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism, divided into three doses at 8-hour intervals 1.
• This patient's free T3 is more than double the upper limit of normal (14.85 vs. 7 pg/mL) and free T4 is at the upper limit (20.65 vs. 20 ng/dL), indicating moderately severe disease warranting 30–40 mg daily 1.
• The total daily dose should be divided into three administrations approximately 8 hours apart to maintain consistent drug levels 1.

Expected Clinical Course and Monitoring

• Untreated hyperthyroidism causes cardiac arrhythmias, heart failure, osteoporosis, adverse pregnancy outcomes, unintentional weight loss, and increased mortality 2.
• Common symptoms include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance 2.
• The maintenance dosage after initial control is typically 5–15 mg daily, representing approximately one-third to one-half of the initial dose 1.

Determining the Underlying Etiology

• Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status 2.
• The most common cause is Graves disease (global prevalence 2% in women, 0.5% in men), which may present with diffusely enlarged thyroid, stare, or exophthalmos 2.
• Other causes include toxic nodules (which may cause dysphagia, orthopnea, or voice changes from local compression) and the thyrotoxic phase of thyroiditis 2.
• Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear 2.

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting etiology confirmation—the degree of thyroid hormone elevation warrants immediate antithyroid drug therapy 2.
• Avoid underdosing in moderately severe disease, as inadequate initial control prolongs the hyperthyroid state and its cardiovascular and metabolic complications 1, 2.
• Treatment for subclinical hyperthyroidism (low TSH with normal T3 and FT4) is recommended for patients at highest risk, such as those older than 65 years or with persistent TSH <0.1 mIU/L, but this patient has overt disease requiring immediate full-dose therapy 2.
• If free T4 were normal but TSH suppressed, measuring free T3 would be essential to distinguish subclinical hyperthyroidism from T3 thyrotoxicosis, but this patient's elevated free T4 confirms overt hyperthyroidism 3, 4.