Etienne Cavalier (Presenter)
University of Liege
Authorship: Etienne Cavalier
University of Liege, Belgium
| Short Abstract While the activation pathway of vitamin D (VTD) is well known, its catabolism through CYP24A1 or 24-hydroxylase, remains unknown to the vast majority of clinicians. The metabolism product of CYP24A1, 24,25(OH)2D, is of great clinical interest because it reflects both vitamin D (VTD) intake and the first step in VTD catabolism and thus the physiologic response to sufficient VTD. It has been shown that changes in serum 24,25(OH)2D are associated with changes in calcium absorption, bone turnover and PTH. The only way to measure 24,25(OH)2D is LC-MS/MS. We have recently published a method for simultaneous measurements of 25(OH)D, 24,25(OH)2D and the Vitamin D Metabolite Ratio (VMR) in serum samples by LC-MS/MS. The assessment of 24,25(OH)2D by LC-MSMS is an under-recognized clinical tool in the evaluation of patients presenting with hypercalcemia and low PTH. |
Long Abstract
While the activation pathway of vitamin D is well known, its catabolism, through CYP24A1, a 24-hydroxylase, remains unknown to the vast majority of clinicians. The metabolism product of CYP24A1, 24,25(OH)2D, is of great clinical interest because it reflects both vitamin D (VTD) intake and the first step in VTD catabolism and thus the physiologic response to sufficient VTD. It has been shown that changes in serum 24,25(OH)2D are associated with changes in calcium absorption, bone turnover and PTH. In 2011, Schlingmann et al identified loss-of-function mutations in CYP24A1 in a population of children presenting with idiopathic infantile hypercalcemia. Most of these children were receiving VTD supplementation, which suggested an unusual sensitivity to VTD. They presented symptomatic hypercalcemia with suppressed PTH associated with nephrocalcinosis. Since then, additional cases have been published and this pattern has been extended to adults with renal disease, nephrolithiasis and nephrocalcinosis. Basically, any patient presenting hypercalcemia with low PTH, and especially patients with nephrocalcinosis or renal stones should undergo 24,25(OH)2D measurement. Indeed, CYP24A1 mutations are now recognized, among other clinical situations (PTHrP, granulomatosis, lymphoma, VTD intoxication, calcium excess, etc) as an important cause of hypercalcemia with suppressed or low PTH. The only way to measure 24,25(OH)2D is by LCMS/MS. We have recently published a fast and simple method for simultaneous measurements of 25(OH)D, 24,25(OH)2D and the Vitamin D Metabolite Ratio (VMR) in serum samples. Since a couple of years, DEQAS has proposed that participating laboratories routinely running 24,25(OH)2D provide results of the controls. Unfortunately, we observed a large variation between results, showing that standardization is needed.
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