Diagnostic accuracy of the different hormonal tests used for the diagnosis of autonomous cortisol secretion

To evaluate the diagnostic accuracy of the different tests commonly used in the evaluation of adrenal incidentalomas (AIs) for the identification of autonomous cortisol secretion (ACS) and comorbidities potentially related to ACS. In a retrospective study of patients with AIs ≥ 1 cm, we evaluated the diagnostic reliability and validity of the dexamethasone suppression test (DST), urinary free cortisol (UFC), ACTH, late-night salivary cortisol (LNSC), and dehydroepiandrosterone-sulphate (DHEAS) for the diagnosis of comorbidities potentially related to ACS. Diagnostic indexes were also calculated for UFC, ACTH, LNSC, and DHEAS considering DST as the gold standard test for the diagnosis of ACS, using three different post-DST cortisol thresholds (138 nmol/L, 50 nmol/L and 83 nmol/L). We included 197 patients with AIs in whom the results of the five tests abovementioned were available. At diagnosis, 85.9% of patients with one or more AIs had any comorbidity potentially related to ACS, whereas 9.6% had ACS as defined by post-DST cortisol > 138 nmol/L. The reliability of UFC, ACTH, LNSC, and DHEAS for the diagnosis of ACS was low (kappa index < 0.30). Of them, LNSC reached the highest diagnosis accuracy for ACS identification (AUC = 0.696 [95% CI 0.626-0.759]). The diagnostic performances of these tests for comorbidities potentially related to ACS was poor; of them, the DST was the most accurate (AUC = 0.661 [95% CI 0.546-0.778]) and had the strongest association with these comorbidities (OR 2.6, P = 0.045). Patients presenting with increased values of both DST and LNSC had the strongest association with hypertension (OR 7.1, P = 0.002) and with cardiovascular events (OR 3.6, P = 0.041). In conclusion, LNSC was the test showing the highest diagnosis accuracy for the identification of ACS when a positive DST was used as the gold standard for its diagnosis. The DST test showed the strongest association with comorbidities potentially related to ACS. The definition of ACS based on the combination of elevated DST and LNSC levels improved the identification of patients with increased cardiometabolic risk.