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

提出的证据表明：a)该病的发病基础 吸收性高钙尿综合征是一种对 1，25-二羟基维生素D(1，25-OH)2D生产，b) 高钙尿，显然主要是由钠引起的，是一种常见的临床症状。 综合征，导致高钙尿症 一半的患者被发现在他们的习惯饮食中有高钙尿症， 以及c)天生的甲状旁腺抑制能力可能是一个重要的 原发性甲状旁腺功能亢进症的病理生理特点。 该提案的具体目的有五个：1)剖析 吸入性痴呆患者1，25-(OH)2D产生的紊乱控制 涉及去磷、甲状旁腺的高钙尿症 激素(PTH)输注，以及超生理剂量的挑战 25-羟基维生素D，2)评估对 这些患者的非常规治疗药物(替莫洛尔和 吲哚美辛)，3)研究生物化学的自然历史 通过在初次诊断后五年重新评估患者的症状，4) 检查表观钠诱导的基础和/或机制 四个仔细定义的研究亚群中的高钙尿症，以及5)至 评价甲状旁腺素-1，25-(OH)2D轴的非反转录抑制能力 原发性甲状旁腺功能亢进症患者钙摄入量增加 在更长期的研究中以及检查和直接比较甲状旁腺 使用该药物的外科候选人在体内和体外的抑制能力 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.