Can radioactive iodine (RAI) cause or worsen Graves' orbitopathy?

Radioactive Iodine and Graves' Orbitopathy

Yes, radioactive iodine (RAI) treatment can cause or worsen Graves' orbitopathy in susceptible individuals, particularly those with pre-existing risk factors.

Mechanism and Risk Factors

Radioactive iodine treatment for hyperthyroidism is associated with the development or exacerbation of Graves' orbitopathy through several mechanisms:

• RAI therapy can trigger an increase in thyroid-stimulating hormone receptor antibodies (TRAbs), which are implicated in the pathogenesis of Graves' orbitopathy 1
• These antibodies bind to TSH receptors in orbital fibroblasts, activating inflammatory pathways that lead to tissue edema and proptosis 2

Key risk factors that increase the likelihood of RAI-induced orbitopathy include:

• Smoking (strongest modifiable risk factor) 3, 2
• Pre-existing mild orbitopathy 4, 1
• High baseline TRAb levels 1
• Recent onset of Graves' disease (duration <5 years) 5
• Post-RAI hypothyroidism, especially if poorly controlled 1

Incidence and Clinical Course

The risk of developing or worsening Graves' orbitopathy after RAI treatment varies across studies:

• Recent data suggests an incidence of approximately 5% for new-onset or worsening orbitopathy after RAI therapy 1
• The risk is higher in patients with pre-existing mild orbitopathy, with studies showing up to 10% risk of severe worsening requiring systemic glucocorticoid treatment 4
• Most cases develop within 3-6 months after RAI administration 6

Prevention and Management

To minimize the risk of RAI-induced orbitopathy:

1. Risk Assessment:

   • Evaluate for pre-existing orbitopathy before RAI treatment
   • Assess risk factors (smoking status, disease duration, TRAb levels)

2. Prophylactic Measures:

   • Glucocorticoid prophylaxis should be administered to high-risk patients, including:
     • Those with pre-existing orbitopathy symptoms
     • Patients with a history of orbitopathy
     • Smokers, even without active orbitopathy 4, 5
   • The most recent evidence shows that both oral and intravenous glucocorticoids are effective in preventing RAI-induced orbitopathy in high-risk patients 5

3. Post-RAI Monitoring:

   • Close monitoring of thyroid function to prevent hypothyroidism
   • Regular ophthalmologic assessment for early detection of orbitopathy

Special Considerations

• Patients receiving RAI for thyroid cancer may also experience worsening of pre-existing orbitopathy, particularly older men, those receiving higher RAI doses, and those not receiving glucocorticoid prophylaxis 7
• Patients with longer disease duration (>5 years) appear to have lower risk of developing orbitopathy after RAI 5

Clinical Pitfalls to Avoid

• Failure to identify high-risk patients: All patients should be assessed for orbitopathy risk factors before RAI therapy
• Inadequate prophylaxis: Not providing glucocorticoid cover to high-risk patients
• Poor post-treatment monitoring: Delayed recognition of hypothyroidism or emerging orbitopathy
• Smoking: Not emphasizing smoking cessation, as it significantly increases orbitopathy risk 3, 2

For patients with moderate-to-severe pre-existing orbitopathy, alternative treatments for hyperthyroidism (antithyroid drugs or surgery) should be considered instead of RAI to avoid potential worsening of eye disease.