Evidence is presented which suggests a) that the pathogenetic basis of the syndrome of absorptive hypercalciuria is a disordered control of 1,25-dihydroxyvitamin D (1,25-OH)2D production, b) that """"""""dietary"""""""" hypercalciuria, apparently largely sodium-induced, is a common clinical syndrome, contributing to the hypercalciuria observed in as many as one-half of patients found to be hypercalciuric on their habitual diets, and c) that innate parathyroid suppressibility may be an important pathophysiological feature in patients with primary hyperparathyroidism.
The specific aims of the proposal are five: 1) to dissect out the disordered control of 1,25-(OH)2D production in patients with absorptive hypercalciuria by protocols involving phosphate deprivation, parathyroid hormone (PTH) infusin, and the challenge with supraphysiological dose of 25-hydroxyvitamin D, 2) to evaluate the biochemical responses to other-than-conventional therapeutic agents in these patients (Timolol and Indomethacin), 3) to investigate the biochemical natural history of the syndrome by reevaluating patients five years after initial diagnosis, 4) to examine the basis and/or mechanism of apparent sodium-induced hypercalciuria in four carefully defined study subpopulations, and 5) to evaluate the unanticiapted suppressibility of the PTH-1,25-(OH)2D axis in patients with primary hyperparathyroidism to an increase in calcium intake in longer-term study as well as to examine and directly compare parathyroid suppressibility in vivo and in vitro in surgical candidates with this disease.
| Wysolmerski, J J; Philbrick, W M; Dunbar, M E et al. (1998) Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development. Development 125:1285-94 |
