Vitamin D deficiency in patients with Graves’ disease: probably something more than a casual association

Abstract

In addition to its established role in calcium metabolism and skeletal homeostasis, vitamin D was recently identified as a factor playing a role in both innate and adaptive immunity (reviewed in Ref. [1]). The vitamin D receptor is expressed on monocytes and activated lymphocytes and the biologically active metabolite of vitamin D, i.e., 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], does modulate T cell responses [1]. Studies in animal models of autoimmune diseases consistently showed that the administration of 1,25(OH)2D3 produces selective immunosuppressant effects, as assessed by its ability to either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel disease [2]. Currently available clinical studies report a high prevalence of vitamin D deficiency in patients with several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, and Crohn’s disease [3]. With specific regard to autoimmune thyroid diseases (AITD), available data remain controversial. The administration of 1,25(OH)2D3 had little effect in reducing the severity of experimental autoimmune thyroiditis induced by immunizing CBA mice with thyroglobulin [4]. In a model of experimental Graves’ disease in which mice were immunized with adenovirus encoding for the TSH-receptor gene, BALB/cJ and C57BL/6J mice receiving either a sufficient or a deficient vitamin D diet developed comparable levels of TSH binding inhibitory and thyroid stimulating antibodies [5]. The IgG subclasses of antibodies directed to the TSH-receptor were also similar in mice of either strain, irrespective of the treatment with a vitamin D-deficient or vitamin D-sufficient diet [5]. However, as argued by the authors, it should be considered that in this experiment mice fed a vitamin D deficient diet, in spite of having nearly undetectable serum levels of 25(OH)D, displayed low but detectable concentrations of 1,25(OH)2D. When human studies are taken into account, a high prevalence of vitamin D deficiency was reported both in patients with chronic autoimmune thyroiditis and in those with Graves’ disease [6, 7]. In this issue of Endocrine, Yasuda et al. [8] measured the serum levels of 25(OH) vitamin D in 26 female patients with newly onset Graves’ disease and in 46 healthy female controls. Vitamin D deficiency was diagnosed when laboratory results indicated a serum level below 15 ng/ml. The authors reported significantly lower levels of vitamin D and a greater prevalence of vitamin D deficiency in Graves’ patients as opposed to healthy controls. A significant inverse relationship was found between the circulating concentrations of vitamin D and thyroid volume. This observation would be in line with the finding by Vilarrasa et al. [9] who reported an inverse association between body mass index (which is positively associated with thyroid volume) and circulating 25(OH) vitamin D. On the other hand, Yasuda et al. [8] found no association between the serum levels of 25(OH)D3 and TSH-, FT3-, FT4-, or TSHreceptor antibodies. Although the results of this study are limited by the small number of investigated patients and by its cross-sectional design, some specific comments can be drawn. First, a large Graves’ goiter is associated with a higher rate of relapsing hyperthyroidism after stopping treatment with anti-thyroid drugs [10]. Thus, Graves’ patients bearing large goiters and being less prone to be successfully cured with anti-thyroid drugs, would more M. Rotondi L. Chiovato (&) Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors and Chair of Endocrinology, University of Pavia, Via S. Maugeri 10, 27100 Pavia, Italy e-mail: luca.chiovato@fsm.it