Differential diagnosis of vitamin D ‐related hypercalcemia using serum vitamin D metabolite profiling

AbstractGenetic causes of vitamin D ‐related hypercalcemia are known to involve mutation of 25‐hydroxyvitamin D‐24‐hydroxylaseCYP24A1 or the sodium phosphate co ‐transporterSLC34A1; which result in excessive 1,25 ‐(OH)2D hormonal action. However, at least 20% of idiopathic hypercalcemia (IH) cases remain unresolved. In this case ‐control study, we used precision vitamin D metabolite profiling based on LC‐MS/MS of an expanded range of vitamin D metabolites ‐ to screen German and French cohorts of hypercalcemia patients, to identify patients with altered vitamin D metabolism where involvement ofCYP24A1 orSLC34A1 mutation had been ruled out, and possessed normal 25 ‐OH‐D3:24,25 ‐(OH)2D3 ratios. Profiles were compared to those of hypercalcemia patients with hypervitaminosis D, Williams ‐Beuren syndrome (WBS),CYP24A1 mutation, and normal subjects with a range of 25 ‐OH‐D levels. We observed that certain IH and WBS patients exhibited a unique profile comprising 8‐10‐fold higher serum 23,25,26‐(OH)3D3 and 25 ‐OH‐D3‐26,23‐lactone than normals; as well as very low serum 1,25‐(OH)2D3 (2 ‐5 pg/mL) and elevated 1,24,25‐(OH)3D3, which we interpret implies hypersensitive expression of vitamin D ‐dependent genes, including CYP24A1, as a general underlying mechanism of hypercalcemia in these patients. As serum 25‐OH‐D3 and 24,25 ‐(OH)2D3 remained normal, we excluded the possibility that the aberrant profile was caused by hypervitamino...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research