{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:12:58Z","timestamp":1763536378553,"version":"3.41.2"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>24-hour urine free cortisol(UFC) is a first line test for Cushing syndrome(CS). A new mass spectrometry assay for UFC requires a validated, relevant reference range appropriate to a screening population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Combined retrospective and prospective cohort study in a government health system and tertiary endocrinology clinic, Canada. Participants were patients with potential features of CS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The refineR reference interval algorithm was used to derive a middle 95%ile reference interval from 4830 UFC results in non-CS patients, compared with 120 prospective patients where evaluation excluded CS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>UFC and 24-hour urine volume were correlated (r=0.28, p&amp;lt;0.0001). There was no significant difference between the volume-corrected UFC distributions in the prospective vs retrospective populations (p=0.09). UFC distribution was highly skewed (p&amp;lt;0.0001) and showed strong sex interaction. The refineR-generated adult male UFC upper reference limit was 238 nmol\/day (86.3 ug\/day) and for females was 147 nmol\/day (53.3 ug\/day); urine volume-corrected, the upper limits were 89 nmol\/L (32.3 ug\/L) and 91 nmol\/L (32.9 ug\/L) respectively. Applied to both populations, between 3-8% of all results would be flagged high; most are expected to represent non-neoplastic (pseudo)Cushing\u2019s.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We used mass population data, where the prevalence of CS was likely very rare, plus a carefully phenotyped sample where CS was considered but excluded, to derive a validated reference interval for 24-hour UFC by mass spectrometry in populations that reflect real world use of the test. Given the highly-skewed upper tail of the population distribution, it is probable that high test specificity for CS will require multi-modality diagnostic confirmation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf054","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:54:46Z","timestamp":1742198086000},"source":"Crossref","is-referenced-by-count":1,"title":["Big data determination and validation of reference range for 24 hour urine cortisol by LCMS\/MS"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-9360","authenticated-orcid":false,"given":"G A","family":"Kline","sequence":"first","affiliation":[{"name":"Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E S","family":"Venos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Orton","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, BC ,","place":["Canada"]},{"name":"BC Children\u2019s and Women\u2019s Hospital , Vancouver, BC ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,3,17]]},"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvaf054\/62426978\/lvaf054.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvaf054\/62426978\/lvaf054.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:54:46Z","timestamp":1742198086000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article\/doi\/10.1093\/ejendo\/lvaf054\/8081549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvaf054","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"type":"print","value":"0804-4643"},{"type":"electronic","value":"1479-683X"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"article-number":"lvaf054"}}