Autoimmune hyperthyroidism and thyroid eye disease: what is the role of pro-oxidants and antioxidants?

Abstract

There is a growing evidence that increased reactive oxygen generation plays an important role in pathogenesis of autoimmune disorders, including Graves’ hyperthyroidism. It has been shown that decreased level of antioxidant vitamins (A, C and E) return to normal after the achievement of euthyroidism. Combined antioxidant treatment of patients with Graves’ hyperthyroidism showed the same improvement effect as thyrostatic medications in terms of clinical symptoms. Thyroid eye disease (TED) is autoimmune in origin and does not result directly from endocrine hormonal imbalance. It has been proven that derangements of pro-/anti-oxidant enzymes occurs in TED and may stay for a long time after correction of hormonal imbalance. Increased levels of oxidative stress and decreased levels of the antioxidant reserve have been reported in the setting of TED. There are a few studies showing the beneficial effect of different singular or combined antioxidants treatment in patients with TED.

Keywords:

• antioxidants
• graves’ disease
• graves’ ophthalmopathy
• hyperthyroidism
• nicotinamide
• oxidative stress
• pentoxifylline
• selenium
• thyroid eye disease
• vitamin

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There is a growing evidence that increased reactive oxygen species generation plays an important role in pathogenesis of autoimmune disorders.

• Basal metabolic rate and total oxygen consumption increase in hyperthyroidism status.

• Oxidative stress correlates with signs and symptoms of hyperthyroidism.

• Thyroid eye disease (TED) has autoimmune pathophysiologic basis, which continues even after normalization of thyroid status.

• Orbital fibroblasts are the immune target for TED.

• Oxygen free radicals activate proliferation of orbital fibroblasts.

• Smoking exerts its worsening effect on TED with imposing oxidative stress.

• Halting the pro-/anti-inflammatory imbalance in TED with micronutrients such as selenium, pentoxifylline, allopurinol, and nicotinamide can help improve clinical activity and quality of life in some patients with TED.

• Supplementation with antioxidants in the treatment of Graves’ disease is justified, particularly those containing selenium.