ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)
1Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, 2Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy, 3Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
JOINT1139
Background: The dexamethasone suppression test (DST) is essential for assessing hypercortisolism. The cut-off of normal cortisol response after DST was set at 18 ng/ml by an extractive radioimmunoassay in 1989. Since then, poor accuracy and reproducibility were documented for non-extractive automated immunoassays used in routine laboratories. The influence of automated immunoassay performance on assessment of hypercortisolism remains under-investigated. Liquid chromatographytandem mass spectrometry (LCMS/MS) is recommended for accurate and sensitive steroid measurement.
Aim: To compare cortisol measurements from two automated immunoassays with LCMS/MS in paired sera collected at baseline and after DST. To evaluate immunoassay performance in detecting hypercortisolism by the DST.
Methods: We included 477 patients with suspected hypercortisolism or adrenal incidentalomas. Cortisol was measured by Elecsys gen I in 260 (cohort 1), and by Access in 217 (cohort 2) subjects. All samples were measured by a validated LCMS/MS method. We compared cortisol measurements in all samples between immunoassays and LCMS/MS, estimated the prevalence of hypercortisolism according to the established cut-off for cortisol after DST (18 ng/ml) with each method, and performed ROC analyses to determine ideal immunoassay-specific cut-off.
Results: Elecsys gen I measurements were 32.5% and 6.1% higher, whereas Access measurements were −4.7% and −5.9% lower than LCMS/MS in basal and post-DST samples, respectively. Considering the cut-off of 18 ng/ml, Access determined a lower prevalence of hypercortisolism than LCMS/MS in the overall cohort 2 (30.4 vs 36.4%, respectively; P=0.001); similar results were obtained for Elecsys gen I only within the adenoma subgroup of cohort 1 (n=112, 26.8 vs 34.8%, respectively; P=0.049). Using LCMS/MS as the reference, Elecsys gen I determined 3.8% possible false positives and 6.9% possible false negatives in cohort 1. In cohort 2, Access caused 0.5% possible false positives and 6.4% possible false negatives. Accordingly, sensitivity and specificity were 79.6 and 94.2% for Elecsys gen I in cohort 1, and 82.3 and 99.3% for Access in cohort 2, respectively. Ideal hypercortisolism screening effectiveness was obtained at 15 ng/ml for Elecsys gen I (sensitivity: 97.7%; specificity: 80.8%), and 12 ng/ml for Access (sensitivity: 97.5%; specificity: 78.3%).
Conclusions: We observed a variable performance between different immunoassays and sampling conditions. In basal samples, Elecsys gen I largely overestimated cortisol levels, whereas Access was accurate. In post-DST samples, both determined a remarkable under-detection of hypercortisolism when using the recommended 18 ng/ml cut-off. We provided novel immunoassay-specific cut-offs. However, LCMS/MS should be preferred to improve DST specificity and to establish harmonized cut-off.