Unit of Endocrinology and Diabetes, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome; [email protected]
Background: Cushings syndrome (CS) is characterized by inappropriate cortisol secretion and its diagnosis is still challenging for endocrinologist. Nevertheless, CS is a rare condition, making difficult to collect data and establish tests diagnostic performances.
Objectives: Assessing diagnostic performances of Urinary Free Cortisol (UFC) evaluated by liquid chromatography method coupled with tandem mass (LC-MS/MS) and Late Night Salivary Cortisol (LNSC), and proposing high sensitivity and specificity cut off values.
Methods: Among 3712 patients (pts) referred to Policlinico Gemelli, 75 pts diagnosed with CS based on UFC dosage were included: 39 affected by Cushings Disease, 18 by adrenal CS, 9 by adrenal carcinoma, 9 by ectopic ACTH secretion. LNSC was also evaluated in 56 pts diagnosed with CS: 38 affected by Cushings Disease, 11 by adrenal CS, 4 by adrenal carcinoma, 3 by ectopic ACTH secretion. As controls, we evaluated 325 volunteers who underwent UFC and 40 volunteers who underwent LNSC dosage. Pts taking steroidogenesis inhibitors, corticosteroids or with renal impairments were excluded. Mann-Whitney U Test was used to compare quantitative variables between groups. ROC curve and area under ROC curve (AUC) were used to determine tests discriminating capacities and cut off values. Significance level was set at α<0.05.
Results: UFC and LNSC values in CS pts were higher than in controls groups (P<0.01). AUCs identified both tests as highly predictive for CS. We selected 43.5 μg/24h as UFC most accurate cut off value (sens 97% spec 89%). As cut offs, we also analyzed 70 μg/24h (sens 80% spec 100%) and 60 μg/24h (sens 87% spec 94%), already proposed in other studies. We selected 0.3 μg/dl as LNSC most accurate cut off value (sens, spec 100%).
Conclusions: We confirmed UFC (LC-MS/MS) and LNSC as first line tests for CS as suggested by the Endocrine Society, proposing specific diagnostic cut off values, and showed LNSC to have superior diagnostic performance.