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.

Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2013
Total Cost
$744,361
Indirect Cost
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Raff, Hershel; Auchus, Richard J; Findling, James W et al. (2015) Urine free cortisol in the diagnosis of Cushing's syndrome: is it worth doing and, if so, how? J Clin Endocrinol Metab 100:395-7
Nieman, Lynnette K (2015) Cushing's syndrome: update on signs, symptoms and biochemical screening. Eur J Endocrinol 173:M33-8
Lacroix, André; Feelders, Richard A; Stratakis, Constantine A et al. (2015) Cushing's syndrome. Lancet 386:913-27
Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K (2014) Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol 4:739-69
Nieman, Lynette (2014) Pitfalls in the diagnosis and differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 80:333-4
Sharma, S T; Nieman, L K (2013) Is Prolactin Measurement of Value during Inferior Petrosal Sinus Sampling in Patients with ACTH-dependent Cushing's Syndrome? J Endocrinol Invest :
Boyd, Sarita D; Hadigan, Colleen; McManus, Maryellen et al. (2013) Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone. J Acquir Immune Defic Syndr 63:355-61
Abraham, Smita Baid; Abel, Brent S; Rubino, Domenica et al. (2013) A direct comparison of quality of life in obese and Cushing's syndrome patients. Eur J Endocrinol 168:787-93
Neary, Nicola M; Booker, O Julian; Abel, Brent S et al. (2013) Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab 98:2045-52
Nieman, Lynnette; Speiser, Phyllis; Young Jr, William F (2013) Adrenal incidentalomas. J Clin Endocrinol Metab 98:37A-8A

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