ADIPOSE TISSUE DISTR ADIPOKINES & APPETITE REG HORMONES /CUSHING'S DISEASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。库欣病与身体成分的深刻变化有关。这些变化包括中央与外周脂肪沉积的增加。经过手术治疗的库欣，随着时间的推移，身体组成的变化正常化。身体成分的这些变化被认为是由于皮质醇对脂肪组织的直接作用，但新的研究表明，其他激素也可能参与其中。脂肪因子（瘦素和脂联素）以及食欲激素（生长激素释放肽和PYY）似乎在食欲和肥胖中起作用。本研究旨在探讨这些激素在库欣氏症患者体内成分变化中的作用。我们计划随访10例库欣综合征患者手术前后的情况。将进行一次术前访视和两次术后访视，第一次术后访视时患者已接受稳定剂量的类固醇至少6个月，第二次术后访视时患者已停用类固醇至少6个月。我们将测量空腹瘦素和脂联素，以及葡萄糖，胰岛素，PYY和ghrelin在测试餐前和测试餐后30，60，90，120和180分钟。受试者将在试验餐前后完成问卷调查，以测量饥饿和饱腹感水平。我们还将招募10名对照患者，在一次研究访视期间接受这些激素检测。在库欣病患者中，我们将通过全身MRI研究脂肪分布，以将激素水平的变化与库欣病治疗中发生的身体成分变化相关联。 假设1：与BMI匹配的对照组相比，活动性库欣病患者的空腹胃饥饿素水平较低，餐后不能显示正常的抑制，手术治愈后将消退。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cushing's disease is associated with profound body composition changes. These changes include an increase in central versus peripheral fat deposition. After surgical treatment of Cushing's, over time the body composition changes normalize. These changes in body composition are felt to be due to direct actions of cortisol on fat tissue, but new research has shown that other hormones may be involved as well. Adipokines (leptin and adiponectin) as well as appetite hormones (ghrelin and PYY) seem to play a role in appetite and obesity. This study proposes to investigate the role of these hormones in the body composition changes seen in Cushing's. We plan to follow 10 Cushing's patients over time before and after surgical treatment. There will be one pre-operative and two post-operative visits, the first post-operative visit while the patient has been on a stable dose of steroids for at least 6 months and the second while the patient has been off steroids for at least 6 months. We will measure fasting leptin and adiponectin as well as glucose, insulin, PYY, and ghrelin before and at 30, 60, 90, 120, and 180 minutes after a test meal. Subjects will complete a questionnaire before and after the test meal to measure levels of hunger and satiety. We will also recruit 10 control patients to undergo these hormone tests during one study visit. In the Cushing's patients, we will investigate adipose distribution by whole-body MRI, to correlate the changes in hormone levels with body composition changes that occur with treatment of Cushing's disease. Hypothesis 1: Compared to BMI-matched controls, patients with active Cushing's disease will have low fasting ghrelin levels that fail to display normal suppression after a meal, which will resolve after surgical cure.