Specificity of Screening Tests for Cushing's Syndrome in an Overweight and Obese Population

Context: Recent reports suggest a higher prevalence (1-5%) of Cushing's syndrome in certain patient populations with features of the disorder (e. g., diabetes), but the prevalence in the overweight and obese population is not known. Objective: The aim of the study was to evaluate the diagnostic performance of screening tests for Cushing's syndrome in overweight and obese subjects with at least two other features of the disorder. Design and Setting: We conducted a cross-sectional prospective study. Subjects and Methods: A total of 369 subjects (73% female) completed two or three tests: a 24-h urine cortisol, 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 mu g/dl (50 nmol/liter)], tests were repeated and/or a dexamethasone-CRH test was performed. Subjects with abnormal DST results and a low dexamethasone level were asked to repeat the test with 2 mg of dexamethasone. Results: In addition to obesity, subjects had a mean of five to six features of Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities to exclude Cushing's syndrome for subjects who completed three tests were: urine cortisol, 96% [95% confidence interval (CI), 93-98%]; DST, 90% (95% CI, 87-93%); salivary cortisol, 84% by RIA (95% CI, 79-89%) and 92% by liquid chromatography-tandem mass spectrometry (95% CI, 88-95%). The combined specificity (both tests normal) for all combinations of two tests was 84 to 90%, with overlapping CIs. Conclusion: 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. (J Clin Endocrinol Metab 94: 3857-3864, 2009)