Body Composition and the Metabolic Syndrome in Cushing's Disease

描述（由申请人提供）： 本项目旨在通过研究慢性糖皮质激素过量患者的促炎标志物、GH/IGF-1轴和胃肠道食欲激素，进一步了解高皮质醇血症的不良后果。为此，我们计划随访库欣病患者，由于ACTH分泌型垂体瘤，手术治疗前后随时间的变化。该研究计划的具体目的是：1）确定与肥胖BMI匹配和瘦对照相比，库欣病患者是否具有升高的血清促炎标志物; 2）随访GH/IGF-1缺乏的库欣病患者，以确定GH/IGF-1缺乏是否会增加治愈患者的代谢综合征和内脏肥胖的风险; 3）表征食欲以及空腹和餐后总的和活性的ghrelin和PYY，以确定它们在糖皮质激素过量的食欲增加和身体组成异常中的作用;和4）通过全身MRI，相对于脂肪因子瘦素和脂联素，定量身体组成，特别是脂肪组织分布。由于我们有独特的机会接触大量垂体库欣病患者，我们有能力研究高皮质醇血症的这些新的慢性效应。在这样做的过程中，我们希望产生重要的新信息的代谢和身体组成异常所造成的过量糖皮质激素暴露，和一般的内脏肥胖的发病机制。 这个职业发展奖申请的主要总体目标是提供支持，使我能够在指导环境中获得新的研究技能和经验，并最终使我能够发展成为神经内分泌学和垂体疾病领域的成功独立研究人员。我目前的环境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. Pamela Freda博士和Derek LeRoith博士分别是垂体疾病/肢端肥大症和IGF-1/肥胖症领域的高素质和经验丰富的研究人员，并致力于为我提供所需的支持，以实现我的研究计划并发展成为独立的研究者。

DESCRIPTION (provided by applicant): This project aims to further understand the adverse consequences of hypercortisolemia by investigating pro-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-inflammatory markers 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.