What is the role of selenium in the treatment of Graves' disease?

Role of Selenium in the Treatment of Graves' Disease

Selenium supplementation is beneficial for patients with mild Graves' orbitopathy but has not shown significant benefit for Graves' hyperthyroidism itself. 1, 2

Mechanism of Action

Selenium is an essential micronutrient with important roles in:

• Antioxidant defense through selenoproteins, particularly glutathione peroxidase 3
• Thyroid hormone metabolism regulation 3
• Protection against oxidative tissue damage 3, 2

In Graves' disease, selenium's antioxidant properties may help counteract the oxidative stress involved in both hyperthyroidism and orbitopathy pathogenesis 2.

Evidence for Selenium in Graves' Disease

Graves' Orbitopathy

• Strong evidence supports selenium use in mild orbitopathy:

  • Selenium supplementation reduces inflammation and eye-specific symptoms 4
  • Marked improvement in disease-specific quality of life 4
  • Ophthalmology guidelines specifically recommend selenium for patients with milder Thyroid Eye Disease (TED) 3
  • Typical dose: 200 μg daily 4

• Pathophysiological basis:

  • Lower serum selenium levels have been observed in patients with Graves' orbitopathy compared to those without eye involvement 5
  • Selenium levels appear to decrease in parallel with increasing severity of orbitopathy 5

Graves' Hyperthyroidism

• Limited evidence for benefit in hyperthyroidism management:
  • A double-blind, placebo-controlled trial found that supplemental selenium (300 μg/day) did not affect response or recurrence rates in Graves' hyperthyroidism when added to methimazole 6
  • Meta-analyses suggest possible enhancement of biochemical euthyroidism restoration, but these results must be interpreted cautiously due to methodological limitations 4

Clinical Application

When to Consider Selenium Supplementation:

1. Mild Graves' Orbitopathy:

   • Recommended for patients with mild orbitopathy of short duration 4
   • Typical dose: 200 μg daily 4
   • Duration: At least 6 months

2. Selenium Deficiency:

   • Consider testing selenium status in patients with Graves' disease, particularly those with orbitopathy 5
   • Normal plasma selenium concentration is approximately 1.20 μmol/L 3
   • Supplementation indicated when plasma selenium <0.75 μmol/L in patients without inflammatory response 3

Monitoring:

• Blood selenium levels can be measured to determine status 3
• Ideally, plasma glutathione peroxidase-3 should be determined to reflect functional status 3
• Simultaneous determination of CRP and albumin helps with interpretation 3

Important Considerations

• Safety profile: Selenium supplementation at recommended doses (200-300 μg/day) is generally safe 3
• Upper limits: Toxicity may occur at plasma levels of 6-12 μmol/L 3
• Unknown efficacy: The effects of selenium supplementation on moderate-to-severe orbitopathy remain unknown 4
• Primary treatment: Selenium should be considered an adjunct, not a replacement for standard treatments for Graves' disease 1

Practical Recommendations

• For mild Graves' orbitopathy: Add selenium 200 μg daily to standard treatment
• For Graves' hyperthyroidism without orbitopathy: Standard treatment with antithyroid drugs remains the primary approach; selenium supplementation is not routinely recommended based on current evidence 6
• For selenium deficiency: Consider supplementation at 100 μg/day orally; higher doses (up to 400 μg/day IV) may be required for severe deficiency (plasma selenium <0.4 μmol/L) 3

Limitations and Future Directions

• Additional randomized clinical trials with clinically relevant endpoints are needed 4
• Better stratification of which Graves' disease patients are most likely to benefit from selenium supplementation 4
• Research on selenium's role in moderate-to-severe orbitopathy is lacking 4