What is the initial treatment for Graves' disease?

Initial Treatment for Graves' Disease

Methimazole is the preferred antithyroid drug for initial treatment of Graves' disease, with a starting dose of 15-30 mg daily depending on disease severity, aiming to maintain free T4 in the high-normal range. 1, 2

First-Line Antithyroid Drug Therapy

Drug Selection and Dosing

• Methimazole (MMI) is the preferred initial agent for most patients with Graves' disease 1, 2, 3
• For mild to moderate hyperthyroidism (free T4 < 7 ng/dL), start with MMI 15 mg daily 4
• For severe hyperthyroidism (free T4 ≥ 7 ng/dL), start with MMI 30 mg daily 4
• MMI 30 mg daily normalizes free T4 more effectively than lower doses in severe cases, achieving normalization in 96.5% of patients by 12 weeks 4
• Propylthiouracil (PTU) should be reserved for patients intolerant of methimazole, as it has higher rates of hepatotoxicity and is less effective at normalizing thyroid function 5, 4

Monitoring and Dose Adjustment

• Measure free T4 or FTI every 2-4 weeks initially to adjust medication dosage 1
• The goal is to maintain free T4 or FTI in the high-normal range using the lowest possible dosage 6, 1
• Initial laboratory confirmation requires TSH and free T4 or free T4 index to document thyrotoxicosis 1

Symptomatic Management

Beta-Blocker Therapy

• Beta-blockers (propranolol or atenolol) should be initiated for symptomatic relief until antithyroid therapy reduces thyroid hormone levels 6, 1
• Beta-blockers address tachycardia, tremor, and anxiety associated with thyrotoxicosis 6
• Continue beta-blockers until thyroid hormone levels normalize, typically several weeks 6

Supportive Care

• Provide hydration and supportive care for patients with moderate to severe symptoms 6, 1

Critical Safety Monitoring

Adverse Effect Surveillance

• Monitor for agranulocytosis, particularly within the first 90 days of antithyroid drug therapy 1, 7
• If patients develop sore throat and fever, obtain complete blood count immediately and discontinue the thioamide 6
• Other serious adverse effects include hepatitis, vasculitis, and thrombocytopenia 6, 1
• Adverse reactions typically occur within the first 90 days of therapy 7
• MMI 15 mg daily has significantly lower rates of hepatotoxicity compared to MMI 30 mg daily or PTU 300 mg daily 4

Treatment Duration and Follow-Up

• Standard treatment course is 12-18 months for adults 3, 7
• Approximately 50% of patients achieve remission after a 12-18 month course of antithyroid drugs 7
• For children with Graves' disease, a 24-36 month course of MMI is recommended 3

Special Clinical Situations

Pregnancy Considerations

• Women planning pregnancy or in the first trimester should be switched from MMI to PTU due to potential teratogenic effects of MMI 6, 3
• Women with Graves' disease require monitoring for normal heart rate and appropriate fetal growth during pregnancy 6, 1
• The newborn's physician must be informed of maternal Graves' disease due to risk of neonatal thyroid dysfunction 6, 1
• Radioactive iodine is absolutely contraindicated during pregnancy 6, 1, 3

Thyroid Storm

• Thyroid storm presents with fever, tachycardia disproportionate to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia 6, 1
• This life-threatening emergency requires immediate hospitalization and treatment with multiple medications including antithyroid drugs and potassium iodide solutions 1

Common Pitfalls to Avoid

• Do not use PTU as first-line therapy unless methimazole is contraindicated, as PTU has higher hepatotoxicity rates and lower efficacy 4
• Do not start with inadequate doses in severe hyperthyroidism (free T4 ≥ 7 ng/dL), as MMI 15 mg daily is insufficient for rapid normalization 4
• Do not continue methimazole in the first trimester of pregnancy—switch to PTU before conception or immediately upon pregnancy confirmation 6, 3
• Do not delay beta-blocker initiation in symptomatic patients, as symptom control is important while waiting for antithyroid drugs to take effect 6