To our best knowledge, this is the first report showing the decreased vitamin D levels in newly onset GD patients and the significant association between vitamin D status and thyroid volume, a clinical factor related to the pathogenesis of GD. Because it has been reported that vitamin D status is not changed by the treatment for GD [3], it is unlikely that decreased vitamin D status in patients with newly onset GD is induced by hyperthyroidism.
Vitamin D is known for its primary role in bone and mineral homeostasis, and it has been shown recently that its deficiency is associated with various diseases such as cardiovascular disease, cancer, infection, and adiposity as well as osteoporosis [4]. Interestingly, it has been shown recently that vitamin D has potent immunomodulatory effects and plays important roles in the pathogenesis of autoimmune diseases. Vitamin D inhibits the production of Th1 polarizing cytokine (IL-12), thereby indirectly shifting the polarization of T cells from a Th1 toward a Th2 phenotype. In the CD4+ T cell response, vitamin D directly inhibits the production of Th1 cytokines (IL2 and IFN-γ), and enhances Th2 cytokine (IL-4) production [1]. In addition, recent numerous studies have shown the relation of vitamin D and various autoimmune diseases. Vitamin D receptor (VDR) gene polymorphisms and vitamin D status are associated with different autoimmune diseases such as T1DM, MS, and IBD [5–7]. Furthermore, vitamin D supplementation prevented the onset and/or development of several kinds of autoimmune diseases in humans and animal models [1]. These results suggested that vitamin D deficiency might cause the onset and/or development of several kinds of autoimmune diseases.
GD is an autoimmune thyroid disease in which TSH receptor autoantibodies cause hyperthyroidism. The pathogenesis of GD is complicated and involved in multiple genetic and environmental factors. It has been thought that GD occurs with the infiltration of T cells in the thyroid gland as a result of these factors. Subsequently, T cells elaborate various cytokines leading to the production of TSH receptor autoantibodies. Especially, helper T cells produce various cytokines, including IFN-γ which induces thyrocytes to express major histocompatibility complex class II surface HLA-DR antigens and renders them susceptible to immunologic attack. Although HLA-DR antigens are not normally expressed on thyroid cells, in GD, the thyroid follicular cells present HLA-DR antigens on their surface with potential involvement in triggering autoimmune process [2]. Recent studies have demonstrated a role of vitamin D in GD. (i) Vitamin D related gene polymorphisms such as VDR gene and vitamin D binding protein gene are associated with GD. (ii) Vitamin D deficiency modulates Graves’ hyperthyroidism induced by thyrotropin receptor immunization in BALB/c mice. (iii) Vitamin D analog inhibits inflammatory responses in human thyroid cells and T cells [8–12]. Although further study would be necessary to conclude, these and our present results suggest that decreased vitamin D levels may cause the onset and/or development of GD as well as several kinds of autoimmune diseases.
In conclusion, vitamin D levels in female patients with newly onset GD are decreased and significantly associated with thyroid volume. It is noted, however, this study is cross-sectional survey with a small number of subjects, and limited in its ability to conclude that vitamin D status is directly related to the pathogenesis of GD. Therefore, the direct role of vitamin D in patients with GD should be examined by further prospective clinical studies by the treatment of vitamin D and experimental studies.