ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)
Outcome of hypercortisolism screening tests and morning plasma ACTH in the differential diagnosis of ACTH-dependent cushing’s syndrome: results from a large European multicenter study
Mario Detomas 1 , Viola Tröger 1 , Isabel Stüfchen 2 , Isabella Nasi-Kordhishti 3 , Stefan Wolfsberger 4 , Marco Losa 5 , Marcus Quinkler 6 , Barbara Altieri 1 , Martin Fassnacht 1 , Greisa Vila 7 , Jürgen Honegger 3 , Katrin Ritzel 2 & Timo Deutschbein 1,8
1Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany, Würzburg, Germany; 2Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany, Munich, Germany; 3Department of Neurosurgery, University of Tübingen, Tübingen, Germany, Tübingen, Germany; 4Department of Neurosurgery, Medical University of Vienna, Vienna, Austria, Vienna, Austria; 5Department of Neurosurgery, Instituto Scientifico San Raffaele, University Vita-Salute, Milan, Italy;, Milan, Italy; 6Endocrinology in Charlottenburg, Berlin, Germany, Berlin, Germany; 7Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, Vienna, Austria; 8Medicover Oldenburg MVZ, Oldenburg, Germany, Oldenburg, Germany
JOINT4005
Background: The limited availability of CRH in many countries poses a challenge in differentiating ACTH-dependent Cushing’s syndrome (CS). While elevated ACTH and cortisol levels are frequently linked to ectopic CS (ECS), the diagnostic accuracy of standard CS screening tests (CSST) in distinguishing ECS from Cushing’s disease (CD) remains uncertain.
Objective: To evaluate the diagnostic performance of morning plasma ACTH and CSST in differentiating CD from ECS in a large cohort of patients with confirmed ACTH-dependent CS.
Methods: We conducted a retrospective, multicenter study across six European centers. Inclusion criteria: (1) patients with overt ACTH-dependent CS and available morning plasma ACTH and CSST results at initial diagnosis; (2) confirmed diagnosis based on histopathology and/or biochemical findings. Cut-offs were determined using ROC analysis (ECS as reference) and the Youden Index. Results were expressed as multiples of the upper limit of normal (x ULN).
Results: A total of 542 patients (493 CD [91%]; 77% female; median age 43 years) were included. The optimal morning ACTH cut-off was 1.8x ULN (sensitivity 74%, specificity 77%, AUC=0.747 [95% CI 0.688-0.853]). Among CSST, 24-hour urinary free cortisol (24h-UFC) showed the best diagnostic performance (cut-off 5.9x ULN, sensitivity 81%, specificity 79%, AUC=0.869 [95% CI 0.816-0.923]), followed by late-night salivary cortisol (cut-off 6.5x ULN, sensitivity 84%, specificity 71%, AUC=0.855 [95% CI 0.768-0.942]) and the 1mg-dexamethasone suppression test (cut-off 9.9x ULN, sensitivity 83%, specificity 72%, AUC=0.823 [95% CI 0.740-0.906]). In 347 patients (313 CD [90%]) with morning ACTH and at least two CSST available, concordance among the majority of tests resulted in a sensitivity and specificity both of 85%, with a high negative predictive value (98%) but a low positive predictive value (37%). Of note, when test results were evenly discordant, results of CSST were prioritized over ACTH due to their higher AUC values.
Conclusion: While morning ACTH and individual CSST have limited accuracy in distinguishing ACTH-dependent CS subtypes, their combined evaluation can improve the noninvasive diagnostic approach. In particular, concordantly low CSST results strongly suggest the absence of ECS.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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