ABNORMALITIES OF PTH-1,25(OH)2D AXIS & HYPERCALCIURIA

证据表明，a）的发病基础， 吸收性高钙尿综合征是一种 1，25-二羟基维生素D（1，25-OH）2D的产生，B）“膳食” 高钙尿症，显然主要是钠引起的，是一种常见的临床 综合征，导致高钙尿症， 发现一半的患者在他们的习惯饮食中高钙尿， 先天性甲状旁腺抑制可能是一个重要的 原发性甲状旁腺功能亢进症病理生理特点 建议的具体目的有五个：1）剖析 吸收型糖尿病患者1，25-（OH）2D产生的紊乱控制 通过涉及磷酸盐剥夺、甲状旁腺 激素（PTH）输注，并与超生理剂量的 25-羟基维生素D，2），以评估对 在这些患者中使用的非常规治疗药物（噻吗洛尔和 消炎痛），3）研究其生化自然史 综合征通过重新评估患者五年后初步诊断，4）， 检查基础和/或机制的明显钠诱导 在四个仔细定义的研究亚群中的高钙尿症，以及5） 评价PTH-1，25-（OH）2D轴的非预期抑制性， 原发性甲状旁腺功能亢进患者钙摄入量增加 在长期研究中以及检查和直接比较甲状旁腺 在手术候选人体内和体外的抑制性 疾病

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.