{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:37:01Z","timestamp":1792431421299,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T00:00:00Z","timestamp":1498780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Summary<\/jats:title>Background and aim<\/jats:title>Differential diagnosis between Cushing's Disease (CD<\/jats:styled-content>) and Ectopic ACTH<\/jats:styled-content> Syndrome (EAS<\/jats:styled-content>) may be a pitfall for endocrinologists. The increasing use in clinical practice of chromatography and mass spectrometry improves the measurement of urinary free cortisol (UFF<\/jats:styled-content>) and cortisone (UFE<\/jats:styled-content>). We have recently observed that cortisol to cortisone ratio (FE<\/jats:styled-content>r) was higher in a small series of EAS<\/jats:styled-content>; in this study we collected a larger number of ACTH<\/jats:styled-content>\u2010dependent Cushing's Syndrome (CS<\/jats:styled-content>) to study the role of FE<\/jats:styled-content>r to characterize the source of corticotropin secretion.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>High\u2010pressure liquid chromatography with UV<\/jats:styled-content> detection (HPLC<\/jats:styled-content>\u2010UV<\/jats:styled-content>, n=35) or liquid chromatography\u2010tandem mass spectrometry (LC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content>, n=72) were used to measure UFF<\/jats:styled-content>, UFE<\/jats:styled-content> and FE<\/jats:styled-content>r in 83 patients with CD<\/jats:styled-content> and 24 with EAS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>UFF<\/jats:styled-content>, UFE<\/jats:styled-content> and FE<\/jats:styled-content>r levels were higher in EAS<\/jats:styled-content> than in CD<\/jats:styled-content> (UFF<\/jats:styled-content>: 6671 vs 549\u00a0nmol\/24\u00a0hours; UFE<\/jats:styled-content>: 2069 vs 464\u00a0nmol\/24\u00a0hours; FE<\/jats:styled-content>r: 4.13 vs 0.97; all P<\/jats:italic><.001). FE<\/jats:styled-content>r >1.15 (the best ROC<\/jats:styled-content>\u2010based threshold) was able to distinguish CD<\/jats:styled-content> from EAS<\/jats:styled-content> with 75% sensitivity (SE<\/jats:styled-content>) and 75% specificity (SP<\/jats:styled-content>), AUC<\/jats:styled-content> 0.811; results were similar between HPLC<\/jats:styled-content>\u2010UV<\/jats:styled-content> (SE<\/jats:styled-content> 73%, SP<\/jats:styled-content> 79%, AUC<\/jats:styled-content> 0.708) and LC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content> (SE<\/jats:styled-content> 77%, SP<\/jats:styled-content> 73%, AUC<\/jats:styled-content> 0.834; P<\/jats:italic>=.727). The diagnostic accuracy of FE<\/jats:styled-content>r was similar to that of CRH<\/jats:styled-content> test or high\u2010dose dexamethasone suppression test (respectively P<\/jats:italic>=.171 and P<\/jats:italic>=.683), also combined. Finally, FE<\/jats:styled-content>r was able to increase the number of correct diagnosis in patients with discordant dynamic tests.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Urinary FE<\/jats:styled-content>r >1.15 was able to suggest EAS<\/jats:styled-content>, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH<\/jats:styled-content>\u2010dependent CS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13391","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T16:00:32Z","timestamp":1496851232000},"page":"500-507","source":"Crossref","is-referenced-by-count":27,"title":["Diagnostic accuracy of increased urinary cortisol\/cortisone ratio to differentiate ACTH\u2010dependent Cushing's syndrome"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-8716","authenticated-orcid":false,"given":"Filippo","family":"Ceccato","sequence":"first","affiliation":[{"name":"Endocrinology Unit Department of Medicine DIMED University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Trementino","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Universit\u00e0 Politecnica delle Marche Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Barbot","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Department of Medicine DIMED University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department of Medicine DIMED University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Plebani","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department of Medicine DIMED University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Denaro","sequence":"additional","affiliation":[{"name":"Neurosurgery Department of Neurosciences DNS University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Regazzo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Department of Medicine DIMED University Hospital of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Rea","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit Department of Cardiac, Thoracic and Vascular Sciences University Hospital of Padova Padova 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