The Physiology Of Hypercortisolism

虽然体重增加和肥胖几乎是库欣综合征的普遍特征，但我们假设筛查结果在肥胖人群中的特异性较差。 该研究基于一家减肥诊所，招募了至少有两种额外的库欣综合征体征或症状的个体。 369名受试者（73%女性）完成了两项或三项测试：24小时尿皮质醇（UFC）和/或深夜唾液皮质醇和/或1 mg地塞米松抑制试验（DST）。如果任何结果异常（基于实验室参考范围或DST后皮质醇>/= 1.8 ug/dl 50 nmol/l），则重复检测和/或进行地塞米松-CRH（dex-CRH）检测。DST结果异常和地塞米松水平低的受试者被要求用2 mg地塞米松重复测试。我们发现，除了肥胖，受试者平均有5-6个库欣综合征的特征。没有发现有库欣综合征。对于完成3项试验的受试者，排除库欣综合征的试验特异性为：UFC 96% 95 CI：93-98%; DST 90% 95 CI：87-93%;唾液皮质醇84%（RIA 95 CI：79-89%）和92%（LC-MS/MS 95 CI：88- 95%）。两种试验的所有组合的组合特异性（两种试验均正常）为84 - 90%，置信区间重叠。这些数据不支持广泛筛查超重和肥胖受试者的库欣综合征;这些患者的检测结果可能是假异常。 在同一人群中，我们评估了皮质醇对代谢综合征参数的影响，UFC和地塞米松反应与BMI或体重无关。唾液皮质醇随BMI的增加而增加（P < 0.0001），且与男性腰围（rs = 0.28，P = 0.02）和女性收缩压（rs = 0.24，P = 0.0008）相关。地塞米松后皮质醇水平与男性空腹胰岛素（rs =-0.31，P = 0.01）和HOMA-IR（rs =-0.31，P = 0.01）以及女性收缩压（rs = 0.18，P = 0.02）和舒张压（rs = 0.20，P = 0.009）呈弱至中度相关。肥胖受试者的PSS结果高于对照组，但与皮质醇或代谢参数无关。正如预期，WC与空腹胰岛素、HOMA-IR和收缩压相关（校正BMI和性别; P < 0.01）。文献显示皮质醇和代谢参数之间的关系不一致。

Although weight gain and obesity are nearly universal features of Cushings syndrome, we hypothesized that screening results would have poor specificity in an obese population. The study is based in a weight loss clinic and enrolled individuals with at least two additional signs or symptoms of Cushings syndrome. 369 subjects (73% female) completed two or three tests: a 24h urine cortisol (UFC), and/or late-night salivary cortisol, and/or 1 mg dexamethasone suppression test (DST). If any result was abnormal (based on laboratory reference range or cortisol after DST >/= 1.8 ug/dl 50 nmol/l), tests were repeated and/or a dexamethasone-CRH (dex-CRH) test was performed. Subjects with abnormal DST results and a low dexamathasone level were asked to repeat the test with 2mg of dexamethasone. We found that in addition to obesity, subjects had a mean of 5-6 features of Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities to exclude Cushing's syndrome for subjects who completed 3 tests were: UFC 96% 95 CI: 93-98%; DST 90% 95 CI: 87-93%; salivary cortisol 84% by RIA 95 CI: 79-89% and 92% by LC-MS/MS 95 CI: 88-95%. The combined specificity (both tests normal) for all combinations of two tests was 84 to 90%, with overlapping confidence intervals. These data do not support widespread screening of overweight and obese subjects for Cushing's syndrome; test results for such patients may be falsely abnormal. Within the same population we have evaluated the influence of cortisol on parameters of the metabolic syndrome.UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P < 0.0001), and correlated with waist circumference (WC) in men (rs = 0.28, P = 0.02) and systolic BP in women (rs = 0.24, P = 0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (rs = -0.31, P = 0.01) and HOMA-IR (rs = -0.31, P = 0.01) in men and systolic (rs = 0.18, P = 0.02) and diastolic BP (rs = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR, and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.