Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess

The decreased intestinal absorption of calcium and accelerated bone loss associated with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to decreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean±SE) in 13 patients during euglucocorticoidism and during hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxyvitamin D concentrations (22±2- 18±2 ng/ml; P < 0.05) but no significant changes in plasma 1,25-dihydroxyvitamin D (32±8-23±6 pg/ml) or serum immunoreactive parathyroid hormone (21±2-18±2 μleq/ml). Additionally, we studied plasma kinetics of [³H]1,25-dihydroxyvitamin D₃ after intravenous bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessment with a three compartment model showed no significant abnormalities in production rates (hyperglucocorticoid patients 1.2±0.3 μg/d, controls 1.5±0.2 μg/d) or metabolic clearance rates (hyperglucocorticoid patients, 32±3 ml/min; controls, 31±3 ml/min). Moreover, there were no significant differences in cumulative excretion of radioactivity in urine (hyperglucocorticoid patients, 18±2%; controls, 14±2%) or feces (hyperglucocorticoid patients, 60±9%, controls, 54±6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)₂D in humans. Thus, other mechanisms must be postulated to explain satisfactorily the abnormalities of bone structure and intestinal calcium absorption that may occur after chronic glucocorticoid therapy.