What is the recommended workup and treatment for a patient suspected of having Graves' disease?

Graves Disease Workup and Treatment

Initial Diagnostic Workup

For suspected Graves' disease, measure TSH and free T4 as the primary screening tests, followed by TSH receptor antibody (TRAb) testing when clinical features suggest Graves' disease, such as ophthalmopathy or T3 toxicosis. 1

Essential Laboratory Tests

• TSH and Free T4: These are the foundational tests for case detection in symptomatic patients 1
• Total T3: Add this in highly symptomatic patients with minimal FT4 elevations 1
• TSH Receptor Antibody (TRAb) or Thyroid Stimulating Immunoglobulin (TSI): Order when clinical features suggest Graves' disease, particularly with ophthalmopathy or T3 toxicosis 1
• Thyroid Peroxidase (TPO) antibody: Consider for additional diagnostic confirmation 1

Imaging Studies

• Radioactive Iodine Uptake Scan (RAIUS) or Technetium-99m thyroid scan: Obtain when feasible to differentiate Graves' disease from thyroiditis 1
• Thyroid ultrasound with color flow Doppler: Shows typical findings of Graves' hyperthyroidism with diffuse increased vascularity 2

Critical Physical Examination Findings

• Ophthalmopathy or thyroid bruit: These physical examination findings are diagnostic of Graves' disease and should prompt early endocrine referral 1, 3

First-Line Treatment

Methimazole is the preferred initial antithyroid drug for most patients with Graves' disease due to its superior side-effect profile compared to propylthiouracil. 3, 4

Methimazole Protocol

• Standard treatment duration: 12-18 months before attempting drug discontinuation 3, 5
• Monitoring schedule: Check thyroid function every 4-6 weeks initially, then every 2-3 months once stable 3
• Titration goal: Maintain Free T4 in the high-normal range using the lowest possible dose 3
• Expected remission rate: Approximately 50% of patients achieve remission after 12-18 months of therapy 5

When to Use Propylthiouracil Instead

Reserve propylthiouracil for three specific situations only: 3, 6

• Patients intolerant of methimazole
• First trimester of pregnancy (due to teratogenic concerns with methimazole)
• Thyroid storm

Symptomatic Management

Add beta-blockers (propranolol or atenolol) for symptomatic relief of tachycardia, tremor, and anxiety while waiting for antithyroid drugs to take effect. 1, 3

• Non-selective beta-blockers with alpha receptor-blocking capacity are preferred for symptomatic patients 1

Critical Safety Monitoring

Life-Threatening Complication to Watch For

If a patient develops sore throat and fever while on thionamides, obtain a complete blood count immediately and discontinue the drug, as this may indicate agranulocytosis. 3

• Most adverse reactions occur within the first 90 days of therapy 5
• Agranulocytosis and hepatotoxicity are rare but potentially significant complications 5

Alternative Definitive Therapies

Radioactive Iodine (RAI)

• Contraindications: Absolutely contraindicated in pregnancy; confirm non-pregnant status in women of childbearing age 3
• Adverse effects: Associated with development or worsening of thyroid eye disease in 15-20% of patients 5
• Outcome: Results in lifelong hypothyroidism requiring levothyroxine replacement 5
• Consider for: Apparently intractable Graves' disease with large goiter (>40 g) 7

Surgery (Near-Total Thyroidectomy)

Surgery is favored in specific clinical scenarios: 5

• Concomitant suspicious or malignant thyroid nodules
• Coexisting hyperparathyroidism
• Large goiters with moderate to severe thyroid eye disease in patients who cannot tolerate antithyroid drugs
• Women planning pregnancy who wish to avoid teratogenic effects of antithyroid drugs 5

Potential surgical complications include: 5

• Hypoparathyroidism
• Vocal cord paralysis
• Lifelong hypothyroidism requiring levothyroxine replacement

When to Refer to Endocrinology

Endocrinology consultation is recommended in all cases of suspected or confirmed Graves' disease, particularly when: 1

• Ophthalmopathy or thyroid bruit is present 1, 3
• Persistent thyrotoxicosis beyond 6 weeks 1
• Moderate to severe symptoms (Grade 2 or higher) 1

Common Pitfalls to Avoid

• Do not start thyroid hormone before steroids if both adrenal insufficiency and hypothyroidism are present, as this can precipitate adrenal crisis 1
• Monitor for transition to hypothyroidism: Thyroiditis can mimic Graves' disease initially but leads to hypothyroidism, requiring switch to levothyroxine 3
• TRAb levels may not correlate with disease activity: Active Graves' disease may persist even after negative TRAb results; rely on clinical assessment and imaging 2
• Elevated TSH in recovery phase: In asymptomatic patients with normal FT4, monitor for 3-4 weeks before treating to determine if recovery occurs 1