How is Graves' disease diagnosed and managed?

Graves' Disease Diagnosis and Management

Graves' disease is diagnosed by demonstrating suppressed TSH with elevated free T4 (FT4) or free thyroxine index (FTI) in the absence of thyroid nodules, and treatment options include antithyroid drugs (methimazole or propylthiouracil), radioactive iodine, or thyroidectomy, with the choice depending on patient-specific factors including pregnancy status, age, goiter size, and presence of ophthalmopathy. 1

Diagnostic Approach

Clinical Presentation

• Classic hyperthyroid symptoms include tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, weight loss, fatigue, diarrhea, and muscle weakness 1, 2
• Distinctive features specific to Graves' disease include:
  • Ophthalmopathy (eyelid lag or retraction) present in ~50% of patients 1, 3
  • Thyroid bruit on examination (diagnostic finding) 2
  • Pretibial myxedema (localized dermopathy) - rare 1
  • Diffuse goiter 3

Laboratory Confirmation

• Biochemical diagnosis requires: Suppressed TSH with elevated FT4 or FTI in the absence of thyroid mass or nodular goiter 1
• TSH receptor antibodies (TRAbs) confirm the diagnosis when ophthalmopathy is absent 3
• Imaging findings: Diffusely enlarged, heterogeneous, hypervascular thyroid gland with increased Doppler flow 4

Key Differential Diagnosis

• Distinguish from thyroiditis (subacute, postpartum): Thyroiditis causes transient, self-limited hyperthyroidism resolving in weeks, whereas Graves' disease causes persistent hyperthyroidism due to ongoing autoimmune stimulation 2

Management Strategy

First-Line Medical Therapy: Antithyroid Drugs

For non-pregnant adults:

• Methimazole is preferred due to once-daily dosing (longer half-life improves adherence) and similar efficacy to propylthiouracil 5, 6
• Standard course: 12-18 months, achieving remission in approximately 50% of patients 6
• Monitor closely in first 90 days when agranulocytosis and hepatotoxicity typically occur 6

For pregnant women:

• Propylthiouracil is mandatory during first trimester due to limited placental transfer and lower teratogenic risk 2, 7
• Switch to methimazole after first trimester if desired, though propylthiouracil can be continued throughout pregnancy 7
• Target thyroid function at upper range of normal to slightly hyperthyroid to avoid fetal hypothyroidism 7
• Untreated hyperthyroidism increases risk of severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight 1

For breastfeeding women:

• Both antithyroid drugs can be used at lowest effective dose 7

Adjunctive Symptomatic Therapy

• Beta-blockers provide symptomatic relief of tachycardia, tremor, and anxiety 2, 5
• Inorganic iodide decreases thyroid vascularity when preparing for surgery but is not used for long-term management 5

Definitive Therapy Options

Radioactive iodine (RAI):

• Preferred treatment for most adults in the United States - easy to administer, safe, effective, and more affordable than long-term antithyroid drugs 5, 6
• Hypothyroidism is inevitable and requires lifelong levothyroxine replacement 5
• Contraindicated in pregnancy and breastfeeding due to fetal thyroid damage 5, 7
• Worsens or triggers ophthalmopathy in 15-20% of patients 6
• Preferred in patients with: History of arrhythmia, ischemic heart disease, or severe thyrotoxicosis 6

Surgery (near-total thyroidectomy):

• Indicated for:
  • Concomitant suspicious or malignant thyroid nodules 6
  • Coexisting hyperparathyroidism 6
  • Large goiters 6
  • Moderate to severe thyroid eye disease (to avoid RAI worsening) 6
  • Patients who cannot tolerate antithyroid drugs 6
• Timing in pregnancy: Reserved for extreme cases, limited to second trimester if necessary 7
• Risks include: Hypoparathyroidism, vocal cord paralysis (laryngeal nerve damage), and hypothyroidism 5

Critical Management Pitfalls

• Overlooking transition from hyperthyroidism to hypothyroidism during treatment can cause significant morbidity 2
• Delaying treatment of severe ophthalmopathy can lead to permanent vision loss 2
• Thyroid storm is a rare but life-threatening medical emergency affecting <1% of pregnant women with hyperthyroidism, characterized by severe acute exacerbation requiring immediate intervention 1
• Fetal and neonatal complications: Consider fetal thyrotoxicosis in women with history of Graves' disease; antibodies cross the placenta causing potential neonatal immune-mediated thyroid dysfunction 1

Special Population Considerations

Elderly patients (>60 years):

• Consider treatment even with mildly suppressed TSH (0.1-0.45 mIU/L) due to increased cardiovascular mortality risk and atrial fibrillation risk 1
• Definitely treat if TSH <0.1 mIU/L due to risk of atrial fibrillation and bone loss 1

Women planning pregnancy:

• Some opt for definitive therapy (RAI or surgery) before conception to avoid teratogenic effects of antithyroid drugs during pregnancy 6