Body Composition and the Metabolic Syndrome in Cushing's Disease

描述(由申请人提供)： 该项目旨在通过研究慢性糖皮质激素过多患者的促炎标记物、GH/IGF-1轴和胃肠道食欲激素来进一步了解高皮质醇血症的不良后果。为此，我们计划在手术治疗前后跟踪观察由于ACTH分泌肿瘤而导致的库欣病患者。该研究建议的具体目的是：1)确定与体重指数匹配的肥胖和瘦对照组相比，库欣病患者是否有升高的血清促炎标志物；2)跟踪GH/IGF-1缺乏的库欣患者，以确定GH/IGF-1缺乏是否会增加治愈患者患代谢综合征和内脏肥胖症的风险；3)表征食欲和空腹及餐后总和活性的Ghrelin和PYY，以确定它们在食欲增加和糖皮质激素过量的身体构成异常中的作用；以及4)通过全身核磁共振成像，结合脂肪运动、瘦素和脂联素来定量身体成分，尤其是脂肪组织的分布。鉴于我们能够接触到大量的脑垂体性库欣病患者，我们有能力研究这些新的高皮质醇血症的慢性影响。通过这样做，我们希望在糖皮质激素过量暴露引起的代谢和身体成分异常以及内脏肥胖症的一般发病机制方面获得重要的新信息。 这个职业发展奖申请的主要总体目标是提供支持，使我能够在有指导的环境中获得新的研究技能和经验，并最终使我发展成为神经内分泌学和脑垂体疾病领域的一名成功的独立研究人员。我目前的环境非常适合实现这一目标。通过波斯特博士，我可以接触到一大批库欣病患者。我的两位导师Pamela Freda博士和Derek LeRoith博士分别是脑下垂体疾病/肢端肥大症和IGF-1/肥胖症领域的高资质和经验丰富的研究人员，他们致力于为我提供所需的支持，让我继续我的研究计划，并发展成为一名独立的研究员。

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.