Extrarenal synthesis of 1,25-dihydroxyvitamin D: sensitivity to glucocorticoid treatment.
The response of circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] to challenge with vitamin D treatment both before and after 7-10 days of prednisone therapy (25 mg/day) was investigated in five anephric subjects, six patients with chronic renal failure (CRF), two patients with vitamin D intoxication and four patients with hypoparathyroidism. In anephric subjects serum 25-hydroxyvitamin D [25-(OH)D] rose from 58 +/- 48 (SD) to 377 +/- 221 (SD) nmol/l after administration of 150 micrograms of 25-(OH)D3 for 1 month. Serum 1,25-(OH)2D, which was barely detectable in only two out of five patients under basal conditions, rose to 30 +/- 21 pmol/l after 2 weeks of therapy with 25-(OH)D3, but fell to 10 +/- 5 pmol/l during prednisone treatment. In CRF patients circulating 1,25-(OH)2D rose from 37 +/- 24 to 58 +/- 24 pmol/l during 25-(OH)D3 therapy, but fell to 41 +/- 31 pmol/l during prednisone treatment. In two patients with rheumatoid arthritis, hypercalcaemia due to vitamin D intoxication was associated with raised levels of 1,25-(OH)2D (288 and 317 pmol/l). Administration of prednisone resulted in suppression of 1,25-(OH)2D levels (132 and 96 pmol/l respectively) and reduction of serum calcium to within the normal range. In the hypoparathyroid patients prednisone therapy did not affect circulating 25-(OH)D levels but serum 1,25-(OH)2D fell from 192 +/- 42 to 117 +/- 23 pmol/l and serum calcium from 2.41 +/- 0.21 to 2.20 +/- 0.05 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
D002112:Calcifediol / Q000627:therapeutic use; D002117:Calcitriol / Q000096:biosynthesis*; D002118:Calcium / Q000097:blood; D004872:Ergocalciferols / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D007011:Hypoparathyroidism / Q000097:blood; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D011241:Prednisone / Q000627:therapeutic use*; D006435:Renal Dialysis; D014807:Vitamin D / Q000506:poisoning
D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; D014807:Vitamin D; C003564:1,25-dihydroxyergocalciferol; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium; D011241:Prednisone