{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:43:56Z","timestamp":1775555036937,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Differentiating Cushing\u2019s disease (CD) from adrenocorticotropic hormone (ACTH)-independent Cushing\u2019s syndrome (AICS) remains challenging in patients with equivocal ACTH levels. While dynamic testing is frequently required, baseline hormonal measurements may offer a simpler diagnostic approach. We aim to evaluate the diagnostic value of baseline plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) levels and their derived ratios for differentiation between ACTH-dependent and ACTH-independent Cushing\u2019s syndrome, and to propose a diagnostic algorithm based on these parameters. Methods: This retrospective single-centre study included adult patients with endogenous Cushing\u2019s syndrome aged 18\u201375 years who were followed at our institution. Patients with ectopic\/paraneoplastic Cushing\u2019s syndrome were excluded. The AICS group comprised overt adrenal CS and mild autonomous cortisol secretion cases. Morning baseline plasma ACTH (pg\/mL), serum cortisol (\u00b5g\/dL), and serum DHEAS (\u00b5g\/dL) levels were measured and ratios calculated: cortisol-to-ACTH ratio (CAR), DHEAS-to-cortisol ratio (DCR), and CAR-to-DHEAS ratio (CAR\/D). ROC analysis assessed diagnostic performance with age and sex adjustments. Results: A total of 100 patients were included, comprising 43 patients with CD and 57 with AICS. Plasma ACTH demonstrated high diagnostic accuracy for identifying CD with a cut-off of \u226514.65 pg\/mL (sensitivity 100%, specificity 98.25%, AUC 0.998). Serum DHEAS showed strong discriminative power with a cut-off of \u226567.15 \u00b5g\/dL (sensitivity 88.37%, specificity 91.23%, AUC 0.925), achieving high discriminative power after age\u2013sex adjustment at \u226585.59 \u00b5g\/dL (sensitivity 100%, specificity 100%, AUC 0.999). CAR showed good performance in identifying CD with a cut-off of \u22640.75 \u00b5g\/dL per pg\/mL (sensitivity 93.02%, specificity 98.25%, AUC 0.980). CAR\/D demonstrated high diagnostic power with a cut-off of \u22641.54 (sensitivity 95.35%, specificity 98.25%, AUC 0.974), improving after age\u2013sex adjustment to \u22642.36 (sensitivity 97.87%, specificity 96.23%, AUC 0.992). Conclusions: Baseline plasma ACTH, serum cortisol, and serum DHEAS measurements, along with derived ratios\u2014especially CAR and CAR\/D\u2014provide highly accurate differentiation between ACTH-dependent and ACTH-independent Cushing\u2019s syndrome. These widely available measurements may reduce dependence on dynamic testing and improve diagnostic accuracy in patients with equivocal findings.<\/jats:p>","DOI":"10.3390\/jcm15072772","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:09:00Z","timestamp":1775549340000},"page":"2772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Utility of ACTH, Cortisol, DHEAS, and Their Derived Ratios in Cushing\u2019s Syndrome Subtypes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-5817","authenticated-orcid":false,"given":"Ekin Yi\u011fit","family":"K\u00f6ro\u011flu","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Ankara Bilkent City Hospital, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-1603","authenticated-orcid":false,"given":"Abbas Ali","family":"Tam","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-1263","authenticated-orcid":false,"given":"Sevg\u00fcl","family":"Faki","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Ankara Bilkent City Hospital, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-0290","authenticated-orcid":false,"given":"Pervin","family":"Demir","sequence":"additional","affiliation":[{"name":"Bioistatistics and Medical Informatics Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Neslihan","family":"\u00c7uhaci Seyrek","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-9059","authenticated-orcid":false,"given":"Didem","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oya","family":"Topalo\u011flu","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7437-1176","authenticated-orcid":false,"given":"Reyhan","family":"Ersoy","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bekir","family":"\u00c7akir","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Diseases Department, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06800 Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0140-6736(14)61375-1","article-title":"Cushing\u2019s syndrome","volume":"386","author":"Lacroix","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.4158\/EP161721.RA","article-title":"An individualized approach to the evaluation of Cushing syndrome","volume":"23","author":"Sharma","year":"2017","journal-title":"Endocr. 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