What is the treatment for Graves' disease?

Treatment of Graves' Disease

The treatment of Graves' disease should follow a three-tiered approach with antithyroid medications as first-line therapy, followed by radioactive iodine or surgery in cases of treatment failure or specific indications. 1

Initial Diagnostic Workup

• Confirm diagnosis with TSH, Free T4, and consider TSH receptor antibody testing if clinical features suggest Graves' disease (e.g., ophthalmopathy) 1
• Monitor thyroid function every 4-6 weeks during initial treatment phase 1

First-Line Treatment: Antithyroid Medications

Medication Options:

• Methimazole (MMI) is the preferred first-line agent for most patients 2, 3

  • Initial dosing:
    • For mild to moderate disease: 15 mg daily 3
    • For severe disease (FT4 ≥7 ng/dl): 30 mg daily 3
  • Once-daily dosing improves adherence compared to PTU 4

• Propylthiouracil (PTU) is reserved for:

  • Patients intolerant to methimazole 5
  • First trimester of pregnancy 5
  • Thyroid storm situations 1
  • Typical dosing: 300 mg daily (divided doses) 3

Treatment Duration and Protocol:

• Standard protocol: 12-18 months of therapy with monitoring every 4-6 weeks initially, then every 2-3 months once stable 1
• Long-term low-dose therapy: Consider maintenance with low-dose methimazole (2.5-5 mg daily) for patients >35 years old, as this may prevent relapse 6, 7
• Titrate dose based on thyroid function tests, with goal to maintain FT4 in high-normal range using lowest possible dose 1

Adjunctive Therapy:

• Beta-blockers (e.g., propranolol or atenolol) for symptomatic relief of tachycardia, tremor, and anxiety 1
• Close monitoring of thyroid function every 2-3 weeks after diagnosis to catch transition to hypothyroidism in patients with thyroiditis 1

Second-Line Treatment Options

Radioactive Iodine (RAI):

• Indicated when:
  • Antithyroid drugs fail to control hyperthyroidism
  • Patient experiences serious adverse effects from antithyroid drugs
  • Patient prefers definitive treatment 4
• Contraindicated in pregnancy and breastfeeding 1
• Patients should not breastfeed for four months after RAI treatment 1
• Hypothyroidism is an expected outcome requiring lifelong thyroid hormone replacement 4

Thyroidectomy:

• Reserved for patients who:
  • Do not respond to antithyroid medications
  • Have very large goiters
  • Have contraindications to both antithyroid drugs and RAI 1, 4
• Requires preoperative preparation with antithyroid drugs and possibly iodide to reduce vascularity 4
• Risks include hypoparathyroidism, laryngeal nerve damage, and hypothyroidism 4

Management of Special Populations

Pregnancy:

• PTU preferred in first trimester due to lower risk of birth defects 5
• Consider switching to methimazole after first trimester 1
• Goal is to maintain maternal FT4 in high-normal range using lowest possible dose 1
• Monitor closely as medication requirements often decrease in later pregnancy 1

Severe Disease/Thyroid Storm:

• Hospitalize patient for intensive management 1
• Beta-blockers for symptomatic relief 1
• High-dose antithyroid drugs (methimazole or PTU) 1
• Consider additional therapies such as steroids, saturated solution of potassium iodide (SSKI) 1
• Supportive care with hydration 1

Monitoring and Follow-up

• Monitor thyroid function every 2-3 weeks initially, then every 4-6 weeks once stable 1
• Watch for common side effects of antithyroid drugs:
  • Minor: rash, urticaria, arthralgia
  • Major: agranulocytosis (fever, sore throat), hepatotoxicity (abdominal pain, jaundice) 5, 3
• Instruct patients to discontinue medication and seek immediate medical attention if they develop symptoms of agranulocytosis (fever, sore throat) 5

Common Pitfalls to Avoid

• Failing to recognize that PTU has higher risk of hepatotoxicity than methimazole 3
• Not monitoring for transition from hyperthyroidism to hypothyroidism, which is common with thyroiditis 1
• Overlooking ophthalmopathy or thyroid bruit, which are diagnostic of Graves' disease and should prompt early endocrine referral 1
• Using radioactive iodine in pregnant or breastfeeding women 1