{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:40:49Z","timestamp":1786466449020,"version":"build-2736575974"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Clinician Scientist Program on Rare Important Syndromes in Endocrinology"},{"name":"Else Kr\u00f6ner-Fresenius-Stiftung & Eva Luise und Horst K\u00f6hler Stiftung"},{"name":"DFG German Research Foundation","award":["314061271-TRR 205"],"award-info":[{"award-number":["314061271-TRR 205"]}]},{"name":"European Reference Network on Rare Endocrine Conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Limited availability of corticotropin-releasing hormone (CRH) currently complicates the differentiation of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). The diagnostic value of common screening tests in distinguishing Cushing's disease (CD) from ectopic CS (ECS) remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the diagnostic performance of screening tests, alone and in combination, in differentiating CD from ECS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective multicenter study enrolling patients with confirmed ACTH-dependent CS and available screening tests at diagnosis. Data are expressed as multiples of upper limit of normal (\u00d7ULN). Optimal cut-offs were determined using Youden's Index. Combination with composite score models and machine learning algorithm were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 566 patients were included (509 [90%] with CD). The optimal morning ACTH cut-off was 1.8\u00d7ULN (sensitivity 74%, specificity 77%, AUC=0.776 [CI-95% .688\u2013.853]). 24h-urinary free cortisol (24h-UFC) showed the best performance (cut-off 5.9\u00d7ULN, sensitivity 72%, specificity 83%, AUC=0.854 [.816\u2013.923]), followed by the 1\u2005mg dexamethasone suppression test (12.8\u00d7ULN, sensitivity 70%, specificity 86%, AUC=.828 [.740\u2013.906]). Using a composite score, a cut-off of 1.5 yielded 78% sensitivity and 92% specificity (AUC=0.865 [.798\u2013.933]). Combining this score with findings derived from pituitary magnetic resonance imaging (MRI), sensitivity and specificity were 88% and 85% (AUC=0.931 [.887\u2013.974]). Machine learning algorithm (balanced random forest) including screening tests-results yielded a sensitivity of 71% and specificity of 84% (AUC=0.853 [.741-.966]), while including the MRI-findings variant achieved a sensitivity and specificity of 76% and 91% (AUC=0.902 [.805-.999]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining screening tests in composite scoring and machine learning differentiates subtypes of ACTH-dependent CS and offers a potential diagnostic alternative to the CRH stimulation test.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag141","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:58:57Z","timestamp":1785412737000},"page":"250-261","source":"Crossref","is-referenced-by-count":0,"title":["Baseline biochemical evaluation for etiologic differentiation in ACTH-dependent Cushing's syndrome: machine learning and composite score analysis in a multicenter cohort of 566 patients"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-5575","authenticated-orcid":false,"given":"Mario","family":"Detomas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7050","authenticated-orcid":false,"given":"Juan P","family":"Prada Salcedo","sequence":"additional","affiliation":[{"name":"Deptartment of Bioinformatics, University of W\u00fcrzburg, Biocenter\/Am Hubland , 97074 W\u00fcrzburg 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