What are the recommended drug dosages for the treatment of hyperthyroidism?

Hyperthyroidism Drug Dosage Treatment

For overt hyperthyroidism, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, and 60 mg daily for severe disease, divided into three doses at 8-hour intervals, with maintenance dosing of 5-15 mg daily once euthyroid. 1

Initial Dosing Strategy

Methimazole (Preferred First-Line Agent)

Adult dosing based on disease severity:

• Mild hyperthyroidism: 15 mg daily divided into 3 doses 1
• Moderately severe hyperthyroidism: 30-40 mg daily divided into 3 doses 1
• Severe hyperthyroidism: 60 mg daily divided into 3 doses 1

Important dosing considerations:

• The starting dose should not exceed 15-20 mg/day to minimize the dose-dependent risk of agranulocytosis 2
• Higher initial doses (30 mg/day) normalize thyroid function faster than lower doses (15 mg/day), particularly in severe cases with free T4 ≥7 ng/dL 3
• For patients with severe hyperthyroidism (FT4 ≥7 ng/dL), methimazole 30 mg/day achieves euthyroidism more effectively at 8 and 12 weeks compared to 15 mg/day 3
• For mild to moderate disease (FT4 <7 ng/dL), methimazole 15 mg/day is adequate and associated with fewer adverse effects 3

Pediatric dosing:

• Initial: 0.4 mg/kg/day divided into 3 doses at 8-hour intervals 1
• Maintenance: approximately half of the initial dose 1

Propylthiouracil (Second-Line Agent)

PTU should NOT be used as first-line therapy due to risk of severe liver failure requiring transplantation or causing death 2. PTU is only recommended in two specific scenarios:

• During the first trimester of pregnancy 2
• In individuals who have experienced adverse responses to methimazole 2

If PTU must be used:

• Initial dose: 300 mg daily in 3 divided doses 4
• Severe hyperthyroidism or large goiters: May increase to 400 mg daily; occasionally 600-900 mg daily initially 4
• Maintenance dose: 100-150 mg daily 4
• Most cases of severe liver injury were associated with doses ≥300 mg/day 4

Maintenance Therapy

Once euthyroid state is achieved:

• Methimazole maintenance: 5-15 mg daily 1
• Time to achieve euthyroidism averages 16.7 weeks with methimazole 5
• Continue monitoring and adjust dosing based on thyroid function tests 1

Factors Affecting Response Time

Response to methimazole is delayed by:

• Large goiter size 6
• High urinary iodine excretion (≥100 mcg/g creatinine) 6
• Elevated pretreatment thyroid hormone levels (especially T3) 6
• Presence of elevated TSH receptor antibodies 6
• Lower methimazole doses (10 mg vs 40 mg) 6

Expected response rates with methimazole 40 mg/day:

• 64.6% of patients respond within 3 weeks 6
• 92.6% respond within 6 weeks 6

Symptomatic Management

For symptomatic patients during the hyperthyroid phase:

• Beta-blockers: Atenolol 25-50 mg daily, titrated to maintain heart rate <90 bpm if blood pressure allows 7
• Alternative beta-blockers: Propranolol or metoprolol 7
• Non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) if beta-blockers are contraindicated 7
• Monitor closely with symptom evaluation and free T4 testing every 2 weeks 7

Critical Safety Considerations

Common pitfalls to avoid:

• Do not use high-dose corticosteroids routinely for hyperthyroidism (they are not required) 7
• Stop antithyroid drugs at least one week prior to radioiodine therapy to reduce risk of treatment failure 2
• Monitor for agranulocytosis (presents with sore throat and fever); obtain CBC and discontinue drug immediately if suspected 7
• Avoid radioiodine during pregnancy, lactation, and for 4 months before planned conception 8

For Graves' disease specifically:

• If TSH receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely and definitive therapy (radioiodine or thyroidectomy) should be recommended 2
• Treat per standard guidelines when Graves' disease is confirmed 7