ADIPOSE TISSUE, ADIPOKINES & APPETITE REGULATORY HORMONES IN CUSHING'S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 库欣病与深刻的身体成分变化有关。这些变化包括中枢与外周脂肪沉积的增加。库兴氏症手术治疗后，随着时间的推移，身体成分的变化会正常化。这些身体成分的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(Ghrelin和PYY)似乎在食欲和肥胖中发挥作用。这项研究建议调查这些激素在库欣病患者身体成分变化中的作用。我们计划在手术治疗前后跟踪观察20名库欣病患者。将有一次术前访问和两次术后访问，第一次是在患者至少6个月使用稳定剂量类固醇的情况下进行的，第二次是在患者至少停止使用类固醇6个月的情况下进行的。我们将在试验餐前和餐后30、60、90、120和180分钟测定空腹瘦素和脂联素以及血糖、胰岛素、PYY和Ghrelin。受试者将在测试餐前后完成一份问卷，以衡量饥饿和饱腹感的水平。我们还将招募10名对照患者在一次研究访问中接受这些激素测试。在库欣病患者中，我们将通过全身核磁共振研究脂肪分布，以将激素水平的变化与库欣病治疗过程中发生的身体成分变化联系起来。 假设1： 与体重指数匹配的对照组相比，活动期库欣病患者的空腹Ghrelin水平较低，餐后无法表现出正常的抑制，这将在手术治愈后缓解。 假设2： 与体重指数匹配的对照组相比，活动期库欣病患者的空腹PYY水平较低，进食诱导的PYY水平下降，这将在手术治愈后缓解。 假设3： Ghrelin和PYY的异常模式将与未经治疗的库欣患者与对照组相比更高的饥饿感评分和更低的饱腹感评分相关；手术后这将恢复正常。 假设4： 与体重指数匹配的对照组相比，库欣病患者的脂联素将受到相对更多的抑制，而瘦素将相对更高。 假设5： 与对照组相比，库欣病患者的腹部和内脏脂肪将增加。术后体内脂肪分布的正常化将与脂肪因子水平的变化相对应。

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 20 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. Hypothesis 2: Compared to BMI-matched controls, patients with active Cushing's disease will have low fasting PYY levels with a blunted meal-induced rise, which will resolve after surgical cure. Hypothesis 3: Abnormal patterns in ghrelin and PYY will correlate to higher hunger scores and lower satiety scores in untreated Cushing's compared to controls; this will normalize after surgery. Hypothesis 4: Adiponectin will be relatively more suppressed and leptin will be relatively higher in Cushing's disease compared to BMI-matched controls. Hypothesis 5: Abdominal and visceral fat will be increased in Cushing's disease compared to matched controls. Normalization of body fat distribution post-surgery will correspond to changes in adipokine levels.