Six months of cholecalciferol/calcium supplementation had no significant effect on skeletal muscle strength and serum testosterone in young adult males.

Our ex vivo IFN-γ ELISPOT assays demonstrate the presence of CaSR-specific memory CD8+ T cells in the peripheral circulation of patients with IH, suggesting the role of cell-mediated autoimmune responses in the etiopathogenesis of IH.

Context Basal-ganglia calcification (BGC) is common (70%) in patients with chronic-hypoparathyroidism. Interestingly, cortical-gray matter is spared from calcification. The mechanism of BGC, role of hyperphosphatemia and modulation of osteogenic-molecules by PTH in its pathogenesis is not clear. Objective We assessed expression of large repertoire of molecules with pro or anti-osteogenic effects including neuroprogenitor-cells in caudate, dentate and cortical-gray matter from normal autopsy tissues. Effect of high-phosphate and PTH was assessed in an ex-vivo model of BGC using striatum tissue culture of Sprague-Dawley rat. Methods The mRNA and protein expression of 39 molecules involved in multiple osteogenic pathways were assessed in 25 autopsy-tissues using RT-PCR, western-blot and immunofluorescence. The striatal-culture was maintained in hypoparathyroid milieu for 24-days with and without (a) high-phosphate (10 mm/β-glycerophosphate) and (b) PTH (1-34) (50 ng/ml DMEM-F12 media) for their effect on striatal-calcification and osteogenic-molecules. Results Pro-calcification molecules (OSTEONECTIN, β-CATENIN, KLOTHO, FZD4, NT5E, LRP5, WNT3A, COLLAGEN 1-α, and SOX2-positive neuroprogenitor stem cells) had significantly higher expression in the caudate than gray-matter. Caudate-nuclei also had higher expression of anti-osteogenic-molecules (OSTEOPONTIN, CARBONIC ANHYDRASE-II, MGP, SCLEROSTIN, ISG15, ENPP1 and USP18). In ex-vivo model striatum-culture showed increased propensity for calcified nodules with mineral deposition similar to that of bone tissue on fourier-transform infrared spectroscopy, alizarin and Von-Kossa stain. Mineralization in striatal-culture was enhanced by high-phosphate and decreased by exogenous PTH through increased expression of CA-II. Conclusion This study provides a conceptual advance on the molecular mechanisms of BGC and possibility of PTH therapy to prevent this complication in hypoparathyroid milieu.

Context Pathogenesis of idiopathic hypoparathyroidism (IH) is under investigation. Abnormalities in central immune tolerance have yet not been investigated in this condition. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, are tools to assess central T- and B-cell output. Objective We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type 1 diabetes (T1D), and autoimmune thyroiditis (ATs) and healthy controls (HCs). Design Comparative case-control at tertiary care center. Subjects and Methods Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of patients with IH (n = 181, 22 of whom were reassessed after a decade of follow-up) and T1D (n = 133), AT (n = 53), and HC (n = 135) using a quantitative real-time PCR/TaqMan ® probe technique. Results Absolute and relative means of TRECs and KRECs in IH were comparable to HCs, and no differences were found between IH with and without calcium-sensing receptor antibodies or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT, and HCs, whereas AT patients showed lower TRECs and the highest KRECs; these levels showed no noteworthy correlation with thyroid dysfunctions. Conclusion Patients with IH showed TRECs and KRECs comparable to HCs, indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HCs, suggesting impaired central immune tolerance in T1D.