Vitamin D Increases Irisin Serum Levels and the Expression of Its Precursor in Skeletal Muscle.

Irisin is a myokine synthesized by skeletal muscle, which performs key actions on whole-body metabolism. Previous studies have hypothesized a relationship between irisin and vitamin D, but the pathway has not been thoroughly investigated. The purpose of the study was to evaluate whether vitamin D supplementation affected irisin serum levels in a cohort of 19 postmenopausal women with primary hyperparathyroidism (PHPT) treated with cholecalciferol for six months. In parallel, to understand the possible link between vitamin D and irisin, we analyzed the expression of the irisin precursor, Fndc5, in the C2C12 myoblast cell line treated with a biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Our results demonstrate that vitamin D supplementation resulted in a significant increase in irisin serum levels (p = 0.031) in PHPT patients. In vitro, we show that vitamin D treatment on myoblasts enhanced Fndc5 mRNA after 48 h (p = 0.013), while it increased mRNAs of sirtuin 1 (Sirt1) (p = 0.041) and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) (p = 0.017) over a shorter time course. Overall, our data suggest that vitamin-D-induced modulation of Fndc5/irisin occurs through up-regulation of Sirt1, which together with Pgc1α, is an important regulator of numerous metabolic processes in skeletal muscle.

Normocalcemic primary hyperparathyroidism: an update.

Normocalcemic primary hyperparathyroidism (NPHPT) is diagnosed in the setting of elevated PTH concentrations with consistently normal albumin-adjusted and ionized serum calcium levels, in absence of secondary causes for elevated PTH concentrations. In order to confirm persistence of the hyperparathyroid state, PTH levels should be elevated on at least two occasions over a 3 to 6 months period. The prevalence of NPHPT depends on the population studied. Data from different studies are often not comparable; indeed, different criteria have been used to exclude secondary hyperparathyroidism. Notwithstanding such limits, the prevalence of NPHPT in studies including ionized calcium dosage was between 0.5% and 0.7%. Available data suggest that patients with NPHPT are likely to have more skeletal, kidney and metabolic complications compared to healthy subjects, but almost all studies suffer from possible misclassification of patients due to lack of ionized calcium dosage. The management of NPHPT is controversial in part due to lack of solid data about the natural history. However, surgical treatment is currently performed more frequently than in the past, although studies do not show, so far, a clear benefit from intervention.