What is the recommended workup and treatment for Graves' disease?

Workup for Graves' Disease

The recommended workup for Graves' disease should include thyroid function tests (TSH, FT4), TSH receptor antibodies, and clinical evaluation for characteristic signs, while treatment options include antithyroid medications, radioactive iodine, or surgery based on disease severity and patient factors.

Diagnostic Workup

Laboratory Tests

• Initial testing: TSH and Free T4 (FT4) 1

  • Typical findings: Suppressed TSH and elevated FT4
  • Consider adding T3 measurement if T3 toxicosis is suspected

• Confirmatory testing:

  • TSH receptor antibodies (TRAb or TSI) - essential for confirming Graves' disease diagnosis 1
  • Consider thyroid peroxidase antibodies (TPO) - often positive but not specific for Graves'

Imaging

• Thyroid ultrasound: Not required for diagnosis but helpful to:

  • Evaluate thyroid morphology
  • Identify nodules if present
  • Assess thyroid dimensions if radioactive iodine therapy is planned 1

• Radioactive iodine uptake scan: Consider in ambiguous cases to:

  • Differentiate Graves' disease (diffusely increased uptake) from other causes of hyperthyroidism
  • Particularly useful when toxic adenoma or multinodular goiter is suspected 1
  • Doppler ultrasound showing increased thyroid blood flow can be an alternative 1

Clinical Evaluation

• Assess for characteristic signs of Graves' disease:
  • Ophthalmopathy (exophthalmos, lid lag, periorbital edema)
  • Diffuse goiter
  • Pretibial myxedema (rare)
  • Physical examination findings of ophthalmopathy or thyroid bruit are diagnostic of Graves' disease 1

Treatment Options

1. Antithyroid Medications

• First-line options:

  • Methimazole (preferred in most cases) 2
  • Propylthiouracil (preferred in first trimester of pregnancy or in those intolerant to methimazole) 3

• Dosing approach:

  • Goal: Maintain FT4 in high-normal range using lowest possible dose 1
  • Monitor FT4 every 2-4 weeks initially, then adjust dose accordingly 1
  • Typical course: 12-18 months with approximately 50% chance of remission 4

• Monitoring:

  • Watch for potential adverse reactions (especially in first 90 days):
    • Agranulocytosis (presents with sore throat and fever)
    • Hepatotoxicity
    • Vasculitis 1, 4

2. Radioactive Iodine (RAI)

• Indications:

  • Patients who fail or relapse after antithyroid drugs
  • Those who prefer definitive therapy
  • Contraindicated in pregnancy 1, 4

• Considerations:

  • Results in permanent hypothyroidism requiring lifelong levothyroxine
  • May exacerbate thyroid eye disease in 15-20% of patients 4
  • Patients should not breastfeed for four months after treatment 1

3. Surgery (Near-total Thyroidectomy)

• Indications:

  • Large goiters
  • Suspicious thyroid nodules
  • Moderate to severe thyroid eye disease
  • Pregnancy planning (to avoid antithyroid drugs during pregnancy) 4

• Potential complications:

  • Hypoparathyroidism
  • Vocal cord paralysis
  • Requires lifelong levothyroxine replacement 4

Adjunctive Therapy

• Beta-blockers (e.g., propranolol, atenolol):
  • For symptomatic relief of tachycardia, tremor, and anxiety
  • Can be used while waiting for antithyroid drugs to take effect 1

Treatment Algorithm Based on Severity

Mild Symptoms (Grade 1)

• Beta-blockers for symptomatic relief
• Antithyroid medication (methimazole preferred)
• Monitor thyroid function every 2-3 weeks initially 1

Moderate Symptoms (Grade 2)

• Beta-blockers for symptomatic relief
• Antithyroid medication at higher doses
• Consider endocrinology consultation
• Hydration and supportive care 1

Severe Symptoms/Thyroid Storm (Grade 3-4)

• Hospitalization
• Beta-blockers
• High-dose antithyroid drugs
• Consider adding corticosteroids (prednisone 1-2 mg/kg/day)
• Consider inorganic iodide (SSKI)
• Mandatory endocrinology consultation 1

Special Considerations

Pregnancy

• Propylthiouracil preferred in first trimester
• Can switch to methimazole after first trimester
• Goal: Use lowest effective dose to minimize fetal exposure
• Monitor thyroid function every trimester 1

Thyroid Eye Disease

• Assess severity of ophthalmopathy
• Consider early referral to ophthalmology if present
• RAI may worsen eye disease; consider alternative treatments 4

Long-term Follow-up

• After antithyroid drug discontinuation, monitor for relapse
• After RAI or surgery, monitor for hypothyroidism and adjust levothyroxine as needed

Remember that early diagnosis and appropriate treatment are essential to prevent complications from untreated hyperthyroidism, including cardiac arrhythmias, heart failure, and thyroid storm.