What is the initial oral medication for treating hyperthyroidism, particularly in patients with Graves' disease?

Initial Oral Medication for Treatment of Hyperthyroidism

Methimazole is the initial oral medication of choice for treating hyperthyroidism in patients with Graves' disease, started at 10-30 mg daily as a single dose, with propylthiouracil (PTU) reserved only for patients intolerant to methimazole, pregnant women in the first trimester, or those preparing for thyroidectomy when methimazole cannot be used. 1, 2, 3, 4

Why Methimazole is Preferred Over Propylthiouracil

Methimazole has critical advantages that make it the superior first-line agent:

• Lower incidence of severe adverse effects, particularly hepatotoxicity, compared to PTU 2, 3, 4
• Once-daily dosing improves adherence versus PTU's requirement for dosing every 6-8 hours 1, 2
• Greater cost-effectiveness and wider availability 2, 4
• Longer half-life allowing more stable thyroid hormone suppression 4

Initial Dosing Strategy Based on Disease Severity

For moderate hyperthyroidism (free T4 <7 ng/dL):

• Start methimazole 15 mg daily as a single dose 3
• This dose normalizes thyroid function in 86.2% of patients by 12 weeks 3
• Lower doses reduce adverse effects, particularly hepatotoxicity 3

For severe hyperthyroidism (free T4 ≥7 ng/dL):

• Start methimazole 30 mg daily as a single dose 5, 3
• This achieves normalization of free T4 in 96.5% of patients by 12 weeks 3
• For very large goiters or extremely severe cases, doses up to 40 mg daily may be required 5

An alternative regimen for severe cases combines:

• Methimazole 15 mg daily PLUS inorganic iodine 38 mg daily 5
• This combination achieves faster normalization (45.3% by 30 days vs 24.8% with methimazole 30 mg alone) 5
• Discontinue iodine once free T4 normalizes to prevent iodine-induced hypothyroidism 5
• This regimen has fewer adverse effects requiring drug discontinuation (7.5% vs 14.8%) 5

When to Use Propylthiouracil Instead

PTU should ONLY be used in these specific circumstances:

• First trimester of pregnancy to avoid methimazole-associated embryopathy (aplasia cutis, choanal/esophageal atresia) 2
• Patients intolerant to methimazole who cannot undergo surgery or radioactive iodine 1
• Preparation for thyroidectomy in methimazole-intolerant patients 1

PTU dosing when required:

• Initial dose: 100-300 mg every 6-8 hours (300-900 mg total daily) 1, 2
• Maintenance: 100-150 mg daily in divided doses 1
• Critical warning: Most cases of severe liver injury with PTU occurred at doses ≥300 mg/day 1

Treatment Duration and Monitoring

Standard treatment course:

• Continue antithyroid drugs for 12-18 months using titration method 6
• Use the lowest dose that maintains euthyroidism 6
• Monitor thyroid function every 4-6 weeks initially, then every 2-3 months once stable 7

Expected outcomes:

• Approximately 50% of patients will relapse after discontinuation 6
• Relapsed patients should be offered ablative therapy (radioiodine or surgery) 6

Critical Safety Considerations

Before initiating antithyroid drugs:

• Rule out concurrent adrenal insufficiency, as thyroid hormone normalization can precipitate adrenal crisis if cortisol deficiency exists 7, 8
• In patients with suspected central hypothyroidism or hypophysitis, always replace cortisol before treating thyroid dysfunction 7

Monitor for adverse effects:

• Mild hepatotoxicity is more common with PTU than methimazole 3
• Adverse effects requiring drug discontinuation occur in 14.8% with PTU 300 mg vs 7.5% with methimazole 15 mg + iodine 5
• Side effects are generally mild and transient with both drugs 6

Special Populations

Pregnancy and lactation:

• PTU is preferred in first trimester due to lower teratogenic risk 2
• Both drugs are present in breast milk but can be used during lactation 2
• Both have similar placental transfer kinetics 2

Children and adolescents:

• Thionamides are the treatment of choice 6
• PTU is generally not recommended in pediatric patients except when alternatives are inappropriate 1
• For children ≥6 years requiring PTU, start at 50 mg daily with careful upward titration 1

Elderly patients:

• Dose selection should be cautious due to decreased hepatic, renal, and cardiac function 1
• Consider lower initial doses and slower titration 1

Common Pitfalls to Avoid

• Never use PTU as first-line therapy when methimazole is appropriate, given PTU's higher hepatotoxicity risk 3, 4
• Avoid underdosing in severe hyperthyroidism, as methimazole 15 mg is insufficient for free T4 ≥7 ng/dL 3
• Do not continue iodine indefinitely when using combination therapy—stop once euthyroid to prevent hypothyroidism 5
• Never start thyroid treatment before ruling out adrenal insufficiency in patients with suspected hypophysitis or central endocrine dysfunction 7, 8