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

这个子项目是众多研究子项目之一

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.