EFFECT OF DEXAMETHASONE ON APPETITE REGULATION IN ANOREXIA NERVOSA

神经性厌食症是青少年中越来越常见的一种疾病 据报告，女童死亡率高达5- 20%。大多数治疗性 发明集中在精神病学模式上。本研究 建议进行医疗干预。神经性厌食症患者可能 对糖皮质激素（GC）的作用有抵抗力。持续升高 在这些体重不足的患者中， 高皮质醇血症的表现（例如，库兴氏体质， 高血压）。对糖皮质激素的抵抗可能是 普遍存在于大脑中。GC拮抗剂的参与 可以假设是在大脑中产生的或者作用于大脑。 候选者包括神经类固醇（如。孕酮）或 未知物质。疾病发作，可能由精神疾病引发 事件，可能导致这些GC拮抗剂的升高。在此设置中 在GC抵抗中，海马和下丘脑可能感觉到较低的 GC的浓度，并因此通过增加 促肾上腺皮质激素释放激素（CRH）分泌。因此，HPA轴可以 产生更多的GC。CRH的输出更高， 激活垂体促肾上腺皮质激素细胞以继续刺激HPA 轴，以及其他大脑区域的受体。厌食，多动症， 导致性功能下降。 通过抑制过度活跃的HPA轴，希望的结果是降低 CRH水平。如果神经性厌食症是由于GC抵抗和 补偿HPA轴反应，应该可以逆转HPA 外源性GC抑制轴过度激活。期间 外源性GC的管理，应该可以确定 神经性厌食症患者是否存在GC抵抗。患者将 接受地塞米松，一种纯GC激动剂，大约高5倍 每日生理替代剂量。HPA之间的关系 抑制和厌食行为。该研究的目的 是了解内分泌系统的调节和潜在的 神经性厌食症的发病机制

Anorexia Nervosa is an increasingly common disorder among adolescent girls with a reported mortality rate as high as 5-20%. Most therapeutic invterventions have centered on psychiatric modalities. This study proposes a medical intervention. Patients with anorexia nervosa may have a resistance to glucocorticoid (GC) action. Sustained elevations of GC in these underweight patients are maintained without obvious manifestations of hypercortisolemia (eg. Cushingoid habitus, hypertension). The resistance to glucocorticoid could either be generalized or present in the brain. The involvement of a GC antagonist can be postulated that is either made in or acts on the brain. Candidates include neurosteroids (eg. pregnenolone, progesterone) or unknown substances. Disease onset, perhaps triggered by psychiatric events, may result in elevation of these GC antagonists. In this setting of GC resistance, the hippocampus and hypothalamus may sense a lower concentration of GC, and consequently compensate by increasing corticotropin-releasing hormone (CRH) secretion. The HPA axis may thus be stimulated to produce more GC. Higher output of CRH then results, activating pituitary corticotrophs to continue stimulation of the HPA axis, as well receptors in other brain regions. Anorexia, hyperactivity, and decreased sexual function result. By suppressing an overactive HPA axis, the hoped for result is to lower CRH levels. If anorexia nervosa is due to GC resistance and a compensatory HPA axis response, it should be possible to reverse HPA axis overactivation by suppression with exogenous GC. During administration of exogenous GC, it should be possible to determine whether anorexia nervosa patients have GC resistance. Patients will receive dexamethasone, a pure GC agonist, approximately 5 times higher than a daily physiological replacement dose. A correlation between HPA suppression and anorectic behavior will be made. The aim of the study is to understand regulation of this endocrine system and the underlying pathogenesis of anorexia nervosa.