What is the initial treatment for Graves' disease?

Initial Treatment for Graves' Disease

Methimazole is the preferred first-line treatment for Graves' disease, starting at 15 mg daily, which is equally effective as higher doses but significantly safer. 1, 2, 3

Diagnostic Confirmation Before Treatment

• Confirm diagnosis with TSH (suppressed), Free T4 (elevated), and consider TSH receptor antibody testing if clinical features suggest Graves' disease 1
• Look specifically for ophthalmopathy or thyroid bruit on physical examination—these findings are diagnostic of Graves' disease and warrant early endocrine referral 4, 1

First-Line Pharmacologic Therapy

Methimazole is the antithyroid drug of choice for most patients 1, 2:

• Starting dose: 15 mg daily is recommended over 30 mg daily 1, 3

  • The 15 mg dose achieves euthyroidism in 40% of patients within 3 weeks and 77.5% within 6 weeks 5
  • Agranulocytosis occurs significantly less frequently with 15 mg daily (0.219%) compared to 30 mg daily (0.814%, p < 0.01) 3
  • Both doses are equally effective at controlling thyroid hormone production 6

• Treatment duration: 12-18 months of continuous therapy 1

• Dose titration strategy: Adjust based on thyroid function tests to maintain FT4 in the high-normal range using the lowest possible dose 1

Symptomatic Management

Beta-blockers should be initiated for symptomatic relief 4, 1:

• Use atenolol 25-50 mg daily or propranolol, titrating for heart rate <90 bpm if blood pressure allows 4
• Provides relief from tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization 1

Monitoring Protocol

Thyroid function testing frequency 4, 1:

• Every 2-3 weeks initially after diagnosis to catch the transition to hypothyroidism 4, 1
• Every 4-6 weeks during the initial treatment phase 1
• Every 2-3 months once stable 1

Factors Predicting Delayed Response

Expect slower response to methimazole in patients with 5:

• Large goiters
• High pretreatment T3 levels (>3x normal)
• Urinary iodide excretion ≥100 micrograms/g creatinine
• Elevated TSH receptor antibodies

Critical Pitfalls to Avoid

• Do not miss the transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis—this requires close monitoring every 2-3 weeks 4, 1
• Do not overlook ophthalmopathy or thyroid bruit, as these are diagnostic of Graves' disease and require early endocrine consultation 4, 1
• Do not use radioactive iodine in pregnant or breastfeeding women—it is absolutely contraindicated 1

When to Escalate or Consider Alternatives

Severe symptoms (Grade 3-4) or thyroid storm 4:

• Hospitalize the patient for intensive management
• Continue beta-blockers for symptomatic control
• Consider high-dose antithyroid drugs, steroids, and saturated solution of potassium iodide (SSKI)
• Endocrine consultation is mandatory

Second-line definitive treatments 1:

• Radioactive iodine therapy for patients not responding to antithyroid medications (contraindicated in pregnancy/breastfeeding for 4 months) 1
• Thyroidectomy for very large goiters, non-responders, or those with contraindications to both antithyroid drugs and radioactive iodine 1

Special Population: Pregnancy

• Propylthiouracil is preferred in the first trimester
• Consider switching to methimazole after the first trimester 1
• Goal: maintain maternal FT4 in high-normal range using the lowest possible dose 1