What is the recommended treatment for Graves' hyperthyroidism?

Treatment of Graves' Hyperthyroidism

The recommended first-line treatment for Graves' hyperthyroidism is methimazole (MMI) for a course of 12-18 months, with dose titration based on thyroid function tests to maintain free T4 in the high-normal range using the lowest possible dose. 1, 2

Initial Diagnosis and Evaluation

• Confirm diagnosis with TSH, Free T4, and TSH receptor antibody testing when clinical features suggest Graves' disease 1
• Physical examination findings of ophthalmopathy or thyroid bruit are diagnostic of Graves' disease and should prompt early endocrine referral 1
• Evaluate for common symptoms: tachycardia, tremor, anxiety, heat intolerance, and weight loss 1

First-Line Treatment: Antithyroid Medications

• Methimazole is the preferred first-line agent for most patients with Graves' disease 1, 2
• Initial dosing recommendations:
  • Start with 10-30 mg daily (can be divided into 8-hour intervals for more severe cases) 3, 4
  • The starting dose should not exceed 15-20 mg/day to reduce risk of dose-dependent complications like agranulocytosis 4
• Monitor thyroid function every 4-6 weeks during initial treatment phase, then every 2-3 months once stable 1
• Continue treatment for 12-18 months in adults; 24-36 months in children 2
• For patients with persistently high TSH-R-Ab at 12-18 months, options include:
  • Continue MMI treatment with repeat TSH-R-Ab measurement after an additional 12 months
  • Proceed to definitive therapy with radioactive iodine (RAI) or thyroidectomy 2

Adjunctive Therapy

• Beta-blockers (e.g., atenolol 25-50 mg daily or propranolol) provide symptomatic relief of tachycardia, tremor, and anxiety until thyroid hormone levels normalize 5
• Monitor closely with regular symptom evaluation and free T4 testing every 2 weeks during the hyperthyroid phase 5

Special Populations

• Pregnant women: Switch from methimazole to propylthiouracil during pregnancy planning and first trimester 5, 2
• Women should not breastfeed for four months after treatment with radioactive iodine 5
• For elderly patients or those with cardiovascular disease, start with lower doses of antithyroid medication 1

Second-Line Treatment Options

• For patients who don't respond to antithyroid drugs after 12-18 months or who relapse after completing treatment, definitive therapy is recommended 2, 6
• Options for definitive treatment include:
  • Radioactive iodine (RAI) therapy: Antithyroid drugs should be stopped at least one week prior to treatment 4
  • Total or near-total thyroidectomy: Should be performed by an experienced high-volume thyroid surgeon 2, 4
• Continued long-term low-dose MMI can be considered as an alternative to definitive treatment for patients who relapse 2

Treatment Selection Considerations

• Radioactive iodine is contraindicated in:
  • Pregnancy and breastfeeding 5, 2
  • Patients with active/severe orbitopathy 2
• Steroid prophylaxis is warranted in Graves' patients with mild/active orbitopathy receiving RAI 2
• Thyroidectomy is preferred for:
  • Large goiters with compressive symptoms
  • Suspicious thyroid nodules
  • Patients with severe orbitopathy 2

Common Pitfalls to Avoid

• Failing to monitor for transition from hyperthyroidism to hypothyroidism, which is common with thyroiditis 5
• Using propylthiouracil as first-line therapy (except in first trimester pregnancy) due to risk of severe liver failure 4
• Using radioactive iodine in pregnant or breastfeeding women 5, 2
• Inadequate follow-up monitoring of thyroid function during and after treatment 1

Remission and Relapse

• Approximately 50% of patients experience relapse after completing antithyroid drug therapy 6
• Remission is unlikely if antibodies against the TSH-receptor remain above 10 mU/l after 6 months of antithyroid treatment 4
• Short-term antithyroid drug therapy (4-8 months) has shown similar remission rates to longer courses in some studies 7