Oxidative Stress in Graves’ Disease

Abstract

Increased reactive oxygen species (ROS) generation and the consequent oxidative damage are involved in the development of several diseases, including autoimmune diseases. Graves’ disease is an autoimmune disorder characterized by hyperthyroidism and, less frequently, orbitopathy. Hyperthyroidism is characterized by increased oxidative stress. Untreated hyperthyroidism is associated with an increase of several parameters of oxidative stress and in most studies (but not all) by an increase of antioxidant defense enzymes. Restoration of euthyroidism with antithyroid drug is associated with a reversal of the biochemical abnormalities associated with oxidative stress. Animal and human studies suggest that increased ROS may directly contribute to some clinical manifestation of the disease, including orbitopathy. Antioxidants administered alone improve some clinical signs and symptoms of hyperthyroidism and, when associated with antithyroid drugs, induce a more rapid control of clinical manifestations and a faster achievement of euthyroidism. A large randomized clinical trial has shown that antioxidant supplementation (selenium) may also be beneficial for mild Graves’ orbitopathy.

Evaluation of Serum S100A8/S100A9 Levels in Patients with Autoimmune Thyroid Diseases

“…Increased oxidative stress is known to break down the immunological tolerance, leading to the proapoptotic effect and an inflammation of the thyroid gland (1)(2)(3)(4).…”

Systemic Oxidative Stress to Nucleic Acids Is Unaltered Following Radioiodine Therapy of Patients with Benign Nodular Goiter

“…A post- 131 I therapy increase in cardiovascular death - per se being associated with oxidative stress - mainly in the first year after treatment [25] has also been reported, but this may be caused by the hyperthyroid state per se, rather than by the 131 I therapy [26]. Indeed, hyperthyroidism may lead to a higher oxidative stress load, but the antioxidant protective enzymes are upregulated as well [27]. Nevertheless, animal as well as human studies suggest that increased free oxygen radicals may be responsible for some manifestations of hyperthyroid diseases and Graves' orbitopathy [27,28].…”

“…Indeed, hyperthyroidism may lead to a higher oxidative stress load, but the antioxidant protective enzymes are upregulated as well [27]. Nevertheless, animal as well as human studies suggest that increased free oxygen radicals may be responsible for some manifestations of hyperthyroid diseases and Graves' orbitopathy [27,28]. Thus, it has been shown that the urinary excretion of the DNA metabolite 8-hydroxy-2'-deoxyguanosine is increased in patients with Graves' orbitopathy, and this correlates with the disease activity and smoking status [29].…”

A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease

“…Hyperthyroidism, especially when untreated, is associated with increases in several oxidative stress parameters, and serum Se concentration is reportedly lower in GD patients than in controls [24,25] . Several studies have indicated that euthyroid patients with active GO show elevated oxidative status markers compared to GD patients without GO, suggesting the importance of the active orbital inflammatory process and the involvement of oxidative stress in GO pathogenesis.…”