CRH'S ROLE IN CAUSE AND RECOVERY FROM HYPERCORTISOLISM

CRH 在皮质醇增多症的病因和恢复中的作用

• 批准号: 2145275
• 负责人: DAVID N ORTH
• 金额: $ 18.37万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-15 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145275
• 关键词: Cushing's syndrome; adrenocorticotropic hormone; alcoholism /alcohol abuse; corticotropin releasing factor; diagnostic tests; endocrine disorder diagnosis; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; major depression; naloxone; neuroendocrine system; pituitary adrenal axis

The clinical conditions associated with hypercortisolism can be divided into two broad categories: Cushing's syndrome and Pseudo-Cushing' s syndrome. Cushing ' s syndrome is hypercortisolism leading to a predictable pattern of clinical sequelae, including obesity, hypertension, glucose intolerance, amenorrhea, osteoporosis, and immune compromise. Pseudo-cushing's syndrome is hypercortisolism in the absence of these clinical manifestations of glucocorticoid excess. With the ability to make the diagnosis of Cushing's syndrome at progressively earlier points in the clinical course, differentiating Cushing's syndrome from pseudo- Cushing's syndrome has become an important clinical issue. Currently, there is no easy way to do this, short of waiting to see if the clinical manifestations of Cushing's syndrome develop in the patient.The common causes of pseudo-Cushing's syndrome include depression, alcoholism, and caloric or physical stress. Recent data suggest that Cushing's syndrome is always CRH independent, while pseudo- Cushing's syndrome is always CRH dependent. This application is based on a hypothesis proposing that two groups can be separated based upon the plasma- adrenocorticocotropic hormone (ACTH) response to an opiate antagonist such as naloxone. Blocking endogenous opiate tone has been shown to enhance ACTH secretion in several animal species. Hence the hypothesis that Naloxone will stimulate ACTH release when CRH are high, and will not affect ACTH secretion when blood level of CRH are low, a strategy likely to separate patients with Cushing's syndrome from those with pseudo-Cushing's syndrome. The results of this study could provide further evidence for a direct role of hypothalamic CRH in the three major disorders of pseudo- Cushing's syndrome and yield new insights into the pathogenesis of these disorders. The investigators also propose to study the recovery of the hypothalamic pituitary-adrenal-axis function following suppression by endogenous or exogenous hypercortisolism.

与皮质醇增多症相关的临床症状可分为 分为两大类：库欣综合征和假性库欣S 综合症。库欣S综合征是一种皮质醇增多症，导致 临床后遗症的可预测模式，包括肥胖、高血压、 葡萄糖不耐受、闭经、骨质疏松症和免疫功能受损。 假性库欣综合征是缺乏这些的皮质醇增多症。 糖皮质激素过量的临床表现。具有以下能力： 在渐进性早期诊断库欣综合征 在临床过程中，鉴别库欣综合征与假性 库欣综合征已成为一个重要的临床问题。目前， 没有简单的方法可以做到这一点，除非等待看看临床 库欣综合征的表现发生在患者身上。常见 假性库欣综合征的原因包括抑郁、酒精中毒和 卡路里或身体压力。最近的数据表明，库欣综合征是 CRH总是非依赖性的，而假性库欣综合征总是CRH 依附的。此应用程序基于一个假设，该假设提出了两个 根据血浆促肾上腺皮质激素水平可以区分不同的群体 激素(ACTH)对阿片类拮抗剂，如纳洛酮的反应。 阻断内源性阿片类物质能促进ACTH的分泌 在几种动物物种中。因此假设纳洛酮会 CRH升高时刺激ACTH释放，不影响ACTH 当血液中CRH水平较低时分泌，这一策略可能会将 库欣综合征患者与假性库欣综合征患者 综合症。这项研究的结果可以提供进一步的证据 下丘脑促肾上腺皮质激素释放激素在假性痴呆三大障碍中的直接作用 库欣综合征及对其发病机制的新认识 精神错乱。调查人员还提议研究找回 下丘脑-垂体-肾上腺轴功能受抑制 内源性或外源性皮质醇增多症。