Body Composition and the Metabolic Syndrome in Cushing's Disease

本项目旨在通过对高皮质醇血症患者的促肾上腺皮质激素释放激素水平的研究， 慢性胰腺炎患者的炎症标志物、GH/IGF-1轴和胃肠道食欲激素 糖皮质激素过量为此，我们计划随访库欣氏病患者，由于促肾上腺皮质激素分泌的垂体 肿瘤，随着手术治疗前后的时间。研究计划的具体目标是：1）确定 与肥胖BMI相比，库欣病患者的血清促炎标志物是否升高- 2）随访GH/IGF-1缺乏的库欣患者，以确定GH/IGF-1缺乏是否 在治愈的患者中赋予代谢综合征和内脏肥胖的增加的风险; 3）表征食欲， 空腹和餐后总和活性ghrelin和PYY，以确定其在食欲增加和异常 糖皮质激素过量的身体组成;和4）量化身体组成，特别是脂肪组织分布， 通过全身MRI，关于脂肪因子瘦素和脂联素。鉴于我们有独特的途径， 垂体库欣病患者人群中，我们有能力研究这些新的慢性效应， 高皮质醇血症在这样做的过程中，我们希望能够获得有关代谢和身体组成的重要新信息 糖皮质激素过量暴露导致的异常，以及一般内脏肥胖的发病机制。 此职业发展奖申请的主要总体目标是提供支持，使我能够 在一个有指导的环境中获得新的研究技能和经验，并最终让我发展成为一个 神经内分泌学和垂体疾病领域的成功独立研究者。我现在的环境是 非常适合实现这一目标。通过波斯特医生，我接触到了一大群库欣氏病患者.我 两位导师Pamela Freda博士和Derek LeRoith博士是以下领域的高素质和经验丰富的研究人员： 垂体疾病/肢端肥大症和IGF-1/肥胖症，并致力于为我提供支持，我 我需要继续我的研究计划，并发展成为一名独立的调查员。 相关性（参见说明）： 目前糖皮质激素的广泛使用导致医源性库欣病的高患病率 综合征，这是与深刻的身体成分的变化，代谢综合征， 增加心血管风险。本提案中概述的研究旨在调查人们知之甚少的 高皮质醇血症引起这些代谢和表型变化的机制。

This project aims to further understand the adverse consequences of hypercortisolemia by investigatingpro- inflammatory markers, the GH/IGF-1 axis, and gastrointestinal appetite hormones in patients with chronic glucocorticoid excess. For this, we plan to follow patients with Cushing's Disease, due to an ACTH-secreting pituitary tumor, over time before and after surgical treatment. The specific aims of the research proposal are to: 1) determine whether patients with Cushing's Disease have elevated serum pro-inflammatorymarkers compared to obese BMI- matched and lean controls; 2) follow GH/IGF-1 deficient Cushing's patients to determine if GH/IGF-1 deficiency confers increased risk for the metabolic syndrome and visceral adiposity in cured patients; 3) characterize appetite and fasting and post-meal total and active ghrelin and PYY to determine their role in the increased appetite and abnormal body composition of glucocorticoid excess; and 4) quantify body composition, particularly adipose tissue distribution, by whole-body MRI, with respect to the adipokines leptin and adiponectin. Given our unique access to a large population of patients with pituitary Cushing's Disease, we have the ability to investigate these novel chronic effects of hypercortisolemia. In doing so, we hope to yield important new information on the metabolic and body composition abnormalities resulting from excess glucocorticoid exposure, and the pathogenesis of visceral adiposity in general. The primary overall objective of this career development award application is to provide support that will enable me to gain new research skills and experience in a mentored environment, and ultimately allow me to develop into a successful independent researcher in the areas of neuroendocrinology and pituitary diseases. My current environment is ideally suited to achieve this goal. Through Dr. Post, I have access to a large cohort of Cushing's Disease patients. My two mentors, Dr. Pamela Freda and Dr. Derek LeRoith, are highly qualified and experienced researchers in the areas of pituitary disease/acromegaly and IGF-1/obesity, respectively, and are committed to providing me with the support I need to pursue my research plans and to develop into an independent investigator. RELEVANCE (See instructions): The current widespread use of glucocorticoids results in a high prevalence of iatrogenic Cushing's Syndrome, which is associated with profound body composition changes, the metabolic syndrome, and increased cardiovascular risk. The studies outlined in this proposal aim to investigate the poorly understood mechanisms by which hypercortisolemia causes these metabolic and phenotypic changes.