Selenium in the Treatment of Graves' Hyperthyroidism and Eye Disease

Abstract

Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism (GH) and Graves' Orbitopathy (GO), a therapy with the antioxidant agent selenium has been proposed and a number of studies have been performed, both in vitro and in vivo. In GH, reactive oxygen species (ROS) contribute to the thyroid and peripheral tissues damage. In GO, tissue hypoxia, as well as ROS, are involved in the typical changes that occur in fibroadipose orbital tissue and the perimysium of extraocular muscles. Antioxidants have been proposed to improve the effects of antithyroid drugs in GH patients, as well as the remodeling of orbital tissues in patients with GO. Here, we reviewed the literature on the possible beneficial effects and clinical use of selenium in the management of patients with GH and GO. A randomized clinical trial on the use of selenium in patients with mild GO provided evidence for a beneficial effect; no data are available on more severe forms of GO. Although the real effectiveness of selenium in patients with GH remains questionable, its use in the management of mild GO is generally believed to be beneficial, and selenium administration has been included in the clinical practice for the patients with mild eye disease.

Keywords: Graves’ hyperthyroidism; Graves’ orbitopathy; oxidative stress; reactive oxygen species; selenium; selenocysteine; selenoproteins.

Figure 1

(A) Effect of selenium (10 μMol) or of the negative control methylcysteine (MCys) (10 μMol) on Glutathione disulfide (GSSG), released after treatment with H₂O₂ (5 μMol), in fibroblasts from patients with Graves’ orbitopathy (GO fibroblasts) or from control patients. P* and **P = 0.02 vs H₂O₂; ‡ and ‡‡ P = NS vs H₂O₂; P = NS between GO and control fibroblasts; (B) Effect of selenium (10 μMol) or methylcysteine (MCys) (10 μMol) on cell proliferation, induced by H₂O₂ treatment (5 μMol), in GO and control fibroblasts. *P = 0.02 vs untreated cells; **P = 0.02 vs H₂O₂; P = 0.003 between GO and control fibroblasts; (C) Effect of selenium (10 μMol) or methylcysteine (MCys) (10 μMol) on hyaluronic acid (HA) release in GO and control fibroblasts. *P = 0.02 vs H₂O₂; P = 0.02 between Graves’ Orbitopathy and control fibroblasts. Reprinted with permission by Thyroid 2017, Volume 27, pp. 271–278, published by Mary Ann Liebert, Inc., New Rochelle, NY.

Figure 2

(A) Clinical Activity Score (CAS) evaluation at baseline and 6 months in patients with mild Graves’ Orbitopathy treated with selenium or placebo; (B) Graves’ orbitopathy-specific quality-of-life questionnaire (GO-QOL) at baseline and 6 months in patients with mild Graves’ Orbitopathy treated with selenium, placebo or Pentoxifylline; (C) Eyelid aperture at baseline and 6 months in patients with mild Graves’ Orbitopathy treated with selenium, placebo or Pentoxifylline; (D) Soft tissue signs at baseline and 6 months in patients with mild Graves’ Orbitopathy treated with selenium, placebo or Pentoxifylline. Redrawn from the Engl J Med 2011; 364: 1920-1931.