What is the management of Graves' disease?

Management of Graves' Disease

The management of Graves' disease should focus on antithyroid medications as first-line therapy, with methimazole being the preferred agent for most patients, while reserving radioactive iodine or surgery for those who fail medical therapy or have specific indications. 1

Diagnosis and Initial Evaluation

• Key diagnostic tests:

  • TSH (typically suppressed)
  • Free T4 or Free T4 Index (elevated)
  • Presence of TSH receptor antibodies (TRAb)
  • Thyroid ultrasound showing diffuse enlargement

• Clinical presentation:

  • Hyperthyroidism symptoms: tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension 2
  • Distinctive features: goiter, ophthalmopathy (in ~50% of patients), pretibial myxedema (rare) 3

Treatment Options

1. Antithyroid Medications

• Methimazole (preferred first-line):

  • Indicated for patients with Graves' disease with hyperthyroidism for whom surgery or radioactive iodine is not appropriate 4
  • Starting dose: 10-40 mg daily based on severity 1
  • Treatment duration: 12-18 months (24-36 months for children) 1
  • Goal: Maintain FT4 or FTI in high-normal range using lowest possible dose 1
  • Monitoring: Every 2-3 weeks initially, then every 4-6 weeks until euthyroid 1

• Propylthiouracil (second-line):

  • Reserved for first trimester of pregnancy, patients intolerant to methimazole, or those with severe liver injury 1, 5
  • Carries higher risk of severe liver problems, including liver failure requiring transplant 5

• Side effects monitoring:

  • Agranulocytosis (rare but serious)
  • Hepatotoxicity
  • Vasculitis
  • Instruct patients to report sore throat, fever, rash, or liver dysfunction symptoms immediately 1

2. Symptomatic Management

• Beta-blockers:
  • For symptomatic relief of tachycardia, tremor, anxiety, heat intolerance
  • Continue until thyroid hormone levels normalize 1
  • Use a graded approach based on symptom severity

3. Definitive Therapy Options

• Radioactive Iodine (RAI):

  • Contraindicated in pregnancy 1
  • Use with caution in patients with active/severe orbitopathy (can worsen eye disease in 15-20% of patients) 6
  • Steroid prophylaxis warranted in patients with mild/active orbitopathy 1
  • Results in hypothyroidism in 70-100% of patients at 10 years, requiring lifelong levothyroxine 7

• Thyroidectomy:

  • Indications: Large goiter, suspicious nodules, coexisting hyperparathyroidism, moderate to severe eye disease 6
  • Should be performed by experienced high-volume thyroid surgeon 1
  • Preparation: Methimazole and potassium iodide solution 1
  • Complications: Hypoparathyroidism, recurrent laryngeal nerve injury (rare with experienced surgeons) 6
  • Highest cure rate (95-100%) in shortest time, but requires lifelong levothyroxine 7

Special Populations

Pregnancy

• Maintain FT4 in high-normal range using lowest possible dose 1
• Propylthiouracil preferred in first trimester, then switch to methimazole 5
• Close monitoring as thyroid dysfunction may diminish as pregnancy proceeds 1
• Untreated maternal hyperthyroidism increases risk for severe preeclampsia, preterm delivery, heart failure, and possibly miscarriage 2

Children

• Longer treatment course (24-36 months) recommended 1
• Methimazole preferred over propylthiouracil due to liver injury risk 1

Follow-up and Monitoring

• Monitor for antithyroid medication side effects regularly
• Long-term monitoring essential even after successful treatment
• For patients with ophthalmopathy, consider selenium supplementation (200 μg daily) 1

Treatment Algorithm

1. Initial therapy: Methimazole + beta-blockers for symptom control
2. If remission achieved after 12-18 months: Trial off medication with close monitoring
3. If relapse occurs or poor response to medical therapy:
   • Consider definitive treatment with RAI (if no significant eye disease)
   • Consider thyroidectomy (if large goiter, suspicious nodules, or significant eye disease)
4. For severe disease: Consider hospitalization, higher doses of antithyroid medications, and additional therapies including steroids, potassium iodide solution, or surgery 1

Remember that approximately 50-70% of patients will relapse after a course of antithyroid drugs, necessitating definitive therapy with either RAI or surgery 8, 6.