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-hydroxy-vitamin 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 muleq/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 micrograms/d, controls 1.5 +/- 0.2 micrograms/d) or metabolic clearance rates (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.
D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D014807:Vitamin D / Q000378:metabolism*
D004100:Dihydroxycholecalciferols; D005938:Glucocorticoids; D010281:Parathyroid Hormone; D014807:Vitamin D