Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Vitamin D and autoimmune thyroid diseases: facts and unresolved questions.

Vitamin D deficiency (levels lower than 20 ng/ml) is becoming a global health problem, since it is increasingly represented even among healthy subjects. Vitamin D, as an environmental factor, is involved in many biological processes, like perception of chronic pain and response to infections. In recent years, evidence has emerged pointing to an involvement of vitamin D in the development of many autoimmune diseases, and a severe vitamin D deficiency has been especially demonstrated in patients affected with autoimmune thyroid disease (AITD). Low levels of vitamin D were found associated with antithyroid antibody presence, abnormal thyroid function, increased thyroid volume, increased TSH levels, and adverse pregnancy outcome in women with AITD. Vitamin D mediates its effect through binding to vitamin D receptor (VDR), which is harbored on many human immune cells, and in this way is able to modulate immune cells activity, triggering both innate and adaptive immune responses. As VDR gene polymorphisms were found to associate with AITD, the evidence links vitamin D deficiency to AITD either through gene polymorphism or by environmental factors (lack of dietary uptake and sun exposure). Vitamin D supplementation may be offered to AITD patients, but further research is needed to define whether it should be introduced in clinical practice.