In the present study, we demonstrated that serum vitamin D levels were significantly lower in female GD patients without remission than in those with remission. To our best knowledge, this is the first report showing the significant difference of vitamin D status between the patients with and without remission of GD. In the present study, we did not evaluate the differences of the severity of hyperthyroidism in onset of GD and duration of hyperthyroidism between the two groups. In addition, durations from the initiation of ATD were significantly longer in non-remission group than in remission group. However, it has been reported that vitamin D status is not related with the severity of hyperthyroidism, and is not changed by the treatment for GD [4, 5]. Therefore, it is unlikely that the significant differences of vitamin D status between the patients with and without remission of GD are attributed to the differences of the severity and duration of hyperthyroidism and duration of the treatment for GD.
Vitamin D is known for its primary role in bone and mineral homeostasis, and its deficiency is associated with cardiovascular disease, cancer, and adiposity as well as osteoporosis . 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 (IL-2 and IFN-γ), and enhances Th2 cytokine (IL-4) production . 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 MS, IBD, and T1DM . Furthermore, vitamin D supplementation prevented the onset and/or development of several kinds of autoimmune diseases in humans and animal models . These results suggest that vitamin D deficiency likely causes the onset and/or development of several kinds of autoimmune diseases.
GD is an autoimmune thyroid disease in which TRAb causes hyperthyroidism. The pathogenesis of GD is complicated and involved in multiple genetic and environmental factors. Recent studies have demonstrated a role of vitamin D in GD. Serum vitamin D levels are decreased and associated with thyroid volume in female patients with new onset GD . Vitamin D-related gene polymorphisms such as VDR gene and vitamin D binding protein gene are associated with GD [7, 8]. Vitamin D deficiency modulates Graves’ hyperthyroidism induced by thyrotropin receptor immunization in BALB/c mice . It is well known that Th1 chemokine CXCL10 plays an important role in the pathogenesis of GD, and that vitamin D analog inhibits CXCL10 in human thyroid cells [10, 11]. In addition, vitamin D analog inhibits inflammatory responses relating to autoimmune process of the development of GD [11, 12]. Although further study would be necessary to conclude, these and our present results suggest that low vitamin D values may influence the development and clinical outcome of GD.
In conclusion, serum vitamin D levels were significantly lower in female GD patients without remission than in those with remission. 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 and/or prognosis 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.