Wednesday, July 15, 2009

Specificity of screening tests for Cushing's syndrome in an overweight and obese population

Smita K. Baid MD, Domenica Rubino MD, Ninet Sinaii PhD, MPH, Sheila Ramsey PhD, Arthur Frank MD,  and Lynnette K. Nieman MD*


The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; The George Washington University Weight Management Program, Washington, DC, USA; Washington Center for Weight Management and Research, Arlington VA, USA; Biostatistics & Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA


* To whom correspondence should be addressed. E-mail:


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: 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: Cross-sectional prospective study.


Subjects and Methods: 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.


Results: 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.


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.


Key words: Cushing's syndrome • dexamethasone • diagnosis • obesity