1,25(OH)2D levels in dihydrotachysterol-treated patients: influence on 1,25(OH)2D assays

Many clinicians continue to prefer dihydrotachysterol (DHT) as the initial vitamin D agent of choice in hypoparathyroidism and renal osteodystrophy because of its long history of efficacy and safety. Assessment of the factors influencing the clinical response to DHT treatment should include measurement of vitamin D metabolite profiles, but investigators have heretofore been unable to measure 1,25(OH)2D because levels have been found to be falsely elevated when employing the chick intestinal cytosol receptor assay. After converting from the chick cytosol receptor assay to the calf thymus receptor assay for measuring 1,25(OH)2D, we did not note falsely elevated levels of 1,25(OH)2D in DHT-treated patients. The design of this study, therefore, was aimed at determining whether or not the calf thymus receptor measured authentic 1,25(OH)2D in such patients. We controlled for the possibility that freezing and thawing or prolonged storage might have either lowered 1,25(OH)2D levels or degraded a metabolite(s) of DHT that would have otherwise been recognized as "1,25(OH)2D" by the calf receptor. Similarly, technical differences between the two assays, source of thymus, and potential interference by other cytosolic proteins were eliminated as causes for the difference between the 1,25(OH)2D levels in the two assays. Our experiments do not provide an explanation for why the thymus receptor does not "see" the interfering metabolite(s) of DHT. This could reflect either a tissue difference or perhaps a species difference. Our results do provide the first opportunity to expand the investigation of the metabolic effects of DHT therapy to include changes in intrinsic 1,25(OH)2D metabolism.