Introduction
Selenium (Se) is a substantially available trace element that plays a broad range of biological roles in human beings. It plays an important role in antioxidant and anti-inflammatory activities and aids in maintaining a healthy metabolism through its role in the production of active thyroid hormone.1 It enters the human food chain through plants, seafood and Se-supplemented animal feed.2 The Se status varies by country and correlates with intake. Se intake is low in Europe and some parts of China and is high in Venezuela, Canada, the USA and Japan.1 The average serum Se levels reported in two different healthy Thai populations were 106.95 ug/L and 114.96 µg/L.3 4 In order to induce the nutritional functions of Se, it is incorporated into selenoproteins with an active centre consisting of selenocysteine. The highest concentration of Se is found in the thyroid gland in the form of glutathione peroxidase 3 (GPX3) that protects thyroid cells from hydrogen peroxide in thyrocytes and the follicular lumen.2 Several systematic reviews and meta-analyses have revealed that Se supplementation could reduce thyroidperoxidase autoantibody concentrations in patients with autoimmune thyroiditis.5–7
Graves’ orbitopathy (GO) is a multifactorial autoimmune disease. It is characterised by the initial reaction against autoantigens present in orbital fibroblasts and thyroid epithelial cells.8 Autoreactive lymphocytes infiltrate orbital tissues and initiate a cascade of inflammatory processes by releasing growth factors, cytokines and reactive oxygen species.9 The pathogenesis ultimately causes the proliferation of orbital fibroblasts that differentiate into adipocytes and myofibroblasts leading to an increased production of hydrophilic glycosaminoglycans.8 9 The volume expansion of orbital tissues leads to proptosis, diplopia, dry eye, optic neuropathy and facial disfigurement. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor autoantibodies have been described as being potentially related to the GO pathogenesis.10 The findings in a randomised control trial of sodium selenite treatment in patients with mild GO included a significantly improved quality of life, less eye involvement and a gradual progression of GO.11 This evidence highlights the importance of Se in treating GO and the possibility that Se supplementation has an effect that reduces oxidative stress and can be used to correct Se deficiency. However, the Se status of patients with GO was not evaluated in the aforementioned study. Based on the results of a case–control study on the serum Se status of patients with Graves’ disease with or without orbitopathy in an Australian population, it was concluded that patients with GO had lower serum Se levels than those with Graves’ disease and that the mean Se levels decreased in parallel with the increasing severity of orbitopathy.12 By contrast, Dehina et al reported on a lack of an association between Se and the severity or activity of GO in German patients.13 To our knowledge, there have been no studies in which Se was identified as an independent risk factor of GO. Therefore, in this study, we aimed to determine whether a relative serum Se deficiency may be a risk factor for the development of severe orbitopathy. In an attempt to identify the relative risk, we aimed to analyse the Se level cut-off point for the diagnosis of mild and severe GO.