Lower circulating levels of 1,25(OH)(2)D(3) are observed in patients with differentiated thyroid carcinoma. Further, while the alleles AA and FF of the ApaI (rs7975232) and FokI (rs10735810) VDR polymorphisms and the haplotype tABF confer to protection from follicular carcinoma, the haplotype Tabf appeared to be associated with an increased FTC risk. Since this is the first report associating VDR polymorphisms with thyroid carcinoma, these findings need to be confirmed in studies with larger numbers of patients.

endocrine regulator [ 5 ] . The active form of VD, 1α,25(OH) 2 D or calcitriol, is synthesised from precursor cholesterol by metabolic steps in skin, liver, and kidney. The primary metabolite, 25OHD, is the most abundant form of VD in blood and therefore established for measuring VD status. Various studies have shown an association of VD status and T2D [ 6 ] . Low 25OHD is found more often in patients with T2D [ 7 , 8 ] and correlates with a higher risk for T2D [ 6 , 9 , 10 ] . Furthermore, the 25OHD serum concentration is negatively associated with components of the metabolic syndrome, such as obesity, hyperglycaemia [ 11 -13 ] , and high body mass index (BMI) [ 9 , 14 -16 ] . Finally, many studies confi rmed an inverse correlation between 25OHD and parameters of insulin resistance: fasting glucose, glucose tolerance, insulin levels, and homeostasis model assessment-index (HOMA-I) [ 17 -24 ] . In addition, interventional studies showed benefi cial eff ects of VD on glucose status, insulin sensitivity, and insulin resistance [ 25 -27 ] . Introduction ▼According to the International Diabetes Federation, more than 300 million people worldwide are currently aff ected by diabetes mellitus ( http://www.idf.org/diabetesatlas/5e/the-globalburden ). A further increase of diabetes prevalence is expected, in particular due to the growing population in developing countries, the increasing industrialisation, urbanisation, and life style changes [ 1 , 2 ] . Diabetes pathophysiology is believed to result from environmental factors on a genetic background, but the causal genes remain complex and exert low hazard risk ratios [ 3 ] . The prevalence of type 2 diabetes (T2D) is infl uenced by multiple environmental factors, one of them may lie in the vitamin D system [ 4 ] . During recent years, vitamin D (VD), mainly known for its eff ects on bone and mineral metabolism, is growingly perceived as a pleiotropic

A higher risk for DTC is conferred by haplotypes within the CYP24A1 gene, low circulating 25(OH)D(3) levels (deficiency), and a reduced conversion to 1,25(OH)(2)D(3). These results confirm and extend previous observations and also support a role of the vitamin D system in the pathogenesis of DTC. How deficient 25(OH)D(3) levels in combination with certain CYP24A1 haplotypes affect vitamin D activation is the subject of future studies.

The mechanisms behind the destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in over 90% of patients, but these autoantibodies are not thought to mediate the disease. Here we demonstrate highly frequent 21-hydroxylase specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8+ and CD4+ T cell responses in a large proportion of Addison’s patients both ex-vivo and after in-vitro culture of peripheral blood lymphocytes up to 20 years after diagnosis. In a large proportion of patients, CD8+ 21-hydroxylase specific T cells and CD4+ 21-hydroxylase specific T cells were very abundant and detectable in ex-vivo assays. HLA class-I tetramer-guided isolation of 21-hydroxylase specific CD8+ T cells showed their ability to lyse 21-hydroxylase positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate strong cytotoxic T lymphocyte responses to 21-hydroxylase often occur in-vivo, and that reactive cytotoxic T lymphocytes have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer.