Elevated production rate of 1,25-dihydroxyvitamin D in patients with absorptive hypercalciuria

Previous studies of 1,25-dihydroxyvitamin D [1,25-(OH)2D] kinetics in normal subjects using the pulse injection technique have led to conflicting results, and only limited data are available concerning 1,25-(OH)2D kinetics in hypercalciuric patients. We developed an infusion equilibrium technique that measures the metabolic clearance and production rates of 1,25-(OH)2D and applied this technique in 13 normal subjects and 9 well characterized patients with absorptive hypercalciuria; all subjects were studied after 10 days on a 400-mg calcium intake. All subjects received a constant infusion of [3H]1,25-(OH)2D3 (20,000 dpm/min). Purified plasma radioactivity reached steady state levels after 15 h, and between 15 and 19 h, serial measurements of purified plasma radioactivity and endogenous 1,25-(OH)2D were made for calculation of metabolic clearance and production rates. In the 13 normal subjects, the MCR values were within a narrow range, with a mean +/- SD value of 37 +/- 6 ml/min, which, when combined with the mean steady state concentration of endogenous 1,25-(OH)2D (42 +/- 6 pg/ml), yielded a mean production rate of 2.2 +/- 0.5 micrograms/day. In the 9 patients with absorptive hypercalciuria, MCR values also were tightly clustered, with a mean of 35 +/- 4 ml/min. However, the mean endogenous steady state 1,25-(OH)2D level was significantly elevated in these patients, such that the calculated mean 1,25-(OH)2D production rate was significantly elevated at 3.4 +/- 0.5 micrograms/day. In 7 of the 9 patients with absorptive hypercalciuria, production rates exceeded the highest values found in the normal subjects. These data demonstrate disordered 1,25-(OH)2D production as opposed to metabolic clearance in the syndrome of absorptive hypercalciuria.