{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:06:23Z","timestamp":1784019983209,"version":"3.55.0"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinica Chimica Acta"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.cca.2026.120909","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T07:41:42Z","timestamp":1771573302000},"page":"120909","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Urinary free cortisol analyses: Enhancing their clinical performance in Cushing's syndrome management by means of LC-MS\/MS"],"prefix":"10.1016","volume":"586","author":[{"given":"Ana","family":"Rubio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Tof\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Barcel\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cca.2026.120909_bb0005","series-title":"J. Clin. Endocrinol. Metab.","first-page":"1526","article-title":"The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline","volume":"93","author":"Nieman","year":"2008"},{"key":"10.1016\/j.cca.2026.120909_bb0010","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing's disease: a guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"10.1016\/j.cca.2026.120909_bb0015","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jsbmb.2019.04.004","article-title":"Performance of LC\u2013MS\/MS and immunoassay based 24 h urine free cortisol","volume":"190","author":"O\u03b2wald","year":"2019","journal-title":"J. Steroid Biochem."},{"key":"10.1016\/j.cca.2026.120909_bb0020","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1258\/acb.2007.007119","article-title":"Measurement of urinary free cortisol by tandem mass spectrometry and comparison with results obtained by gas chromatography-mass spectrometry and two commercial immunoassays","volume":"45","author":"Wood","year":"2008","journal-title":"Ann. Clin. Biochem."},{"key":"10.1016\/j.cca.2026.120909_bb0025","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/0004563216687335","article-title":"Measuring cortisol in serum, urine and saliva \u2013 are our assays good enough?","volume":"54","author":"El-Farhan","year":"2017","journal-title":"Ann. Clin. Biochem."},{"key":"10.1016\/j.cca.2026.120909_bb0030","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1258\/0004563053492775","article-title":"Measurement of urinary free cortisol using liquid chromatography-tandem mass spectrometry: comparison with the urine adapted ACS:180 serum cortisol chemiluminescent immunoassay and development of a new reference range","volume":"42","author":"McCann","year":"2005","journal-title":"Ann. Clin. Biochem."},{"key":"10.1016\/j.cca.2026.120909_bb0035","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s11102-016-0730-5","article-title":"Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome","volume":"19","author":"Aranda","year":"2016","journal-title":"Pituitary"},{"key":"10.1016\/j.cca.2026.120909_bb0040","first-page":"213","article-title":"Cortisol and cortisone ratio in urine: LC-MS\/MS method validation and preliminary clinical application","volume":"52","author":"Antonelli","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"10.1016\/j.cca.2026.120909_bb0045","first-page":"151","article-title":"Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome","volume":"82","author":"Lin","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.cca.2026.120909_bb0050","doi-asserted-by":"crossref","first-page":"558","DOI":"10.3390\/biom14050558","article-title":"LC-HRMS and GC-MS profiling of urine free cortisol, cortisone, 6B-, and 18-hydroxycortisol for the evaluation of glucocorticoid and mineralocorticoid disorders","volume":"14","author":"Casals","year":"2024","journal-title":"Biomolecules"},{"key":"10.1016\/j.cca.2026.120909_bb0055","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1093\/clinchem\/48.9.1511","article-title":"Validation of a high-throughput liquid chromatography\u2013tandem mass spectrometry method for urinary cortisol and cortisone","volume":"48","author":"Taylor","year":"2002","journal-title":"Clin. Chem."},{"key":"10.1016\/j.cca.2026.120909_bb0060","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1210\/er.2018-00262","article-title":"Steroid metabolome analysis in disorders of adrenal steroid biosynthesis and metabolism","volume":"40","author":"Storbeck","year":"2019","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.cca.2026.120909_bb0065","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/cen.13391","article-title":"Diagnostic accuracy of increased urinary cortisol\/cortisone ratio to differentiate ACTH-dependent Cushing's syndrome","volume":"87","author":"Ceccato","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.cca.2026.120909_bb0070","doi-asserted-by":"crossref","DOI":"10.3390\/molecules28010248","article-title":"Simultaneous measurement of cortisol, cortisone, dexamethasone and additional exogenous corticosteroids by rapid and sensitive LC-MS\/MS analysis","volume":"28","author":"Ponzetto","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.cca.2026.120909_bb0075","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.4155\/bio-2018-0182","article-title":"Quantitative profiling of cortisol metabolites in human urine by high-resolution accurate-mass MS","volume":"10","author":"Wang","year":"2018","journal-title":"Bioanalysis"},{"key":"10.1016\/j.cca.2026.120909_bb0080","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.1007\/s00216-022-04249-3","article-title":"Quantification of cortisol and its metabolites in human urine by LC-MSn: applications in clinical diagnosis and anti-doping control","volume":"414","author":"Arioli","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.cca.2026.120909_bb0085","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1046\/j.1365-2265.1996.00853.x","article-title":"Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase activity in man","volume":"45","author":"Palermo","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.cca.2026.120909_bb0090","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-1-0716-2565-1_11","article-title":"Measurement of urinary free cortisol and cortisone by LC-MS\/MS","volume":"2546","author":"Ray","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.cca.2026.120909_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.cca.2025.120324","article-title":"Determination of human urinary cortisol, cortisone and relative phase II metabolites by dilute-and-shoot LC-MS\/MS analysis: an application to adrenal disease","volume":"574","author":"Leoni","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.cca.2026.120909_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.cca.2025.120129","article-title":"Challenges in the diagnosis and follow-up of Cushing's syndrome: evaluating LC-MS\/MS as a confirmation method for urinary free cortisol analyses","volume":"568","author":"Rubio","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.cca.2026.120909_bb0105","author":"Clinical and Laboratory Standards Institute"},{"key":"10.1016\/j.cca.2026.120909_bb0110","author":"Clinical and Laboratory Standards Institute"},{"key":"10.1016\/j.cca.2026.120909_bb0115","author":"European Medicines Agency"},{"key":"10.1016\/j.cca.2026.120909_bb0120","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1575-0922(09)70983-0","article-title":"The medical management of Cushing's syndrome","volume":"56","author":"Leal-Cerro","year":"2009","journal-title":"Endocrinol. Nutr."},{"key":"10.1016\/j.cca.2026.120909_bb0125","first-page":"9","article-title":"Big data and reference intervals: rationale, current practices, harmonization and standardization prerequisites and future perspectives of indirect determination of reference intervals using routine data","volume":"2","author":"Mart\u00ednez-S\u00e1nchez","year":"2020","journal-title":"Adv. Lab. Med."},{"key":"10.1016\/j.cca.2026.120909_bb0130","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/cen.14919","article-title":"Diagnostic accuracy of morning serum cortisol concentration in predicting secondary adrenal insufficiency","volume":"99","author":"Barbar","year":"2023","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.cca.2026.120909_bb0135","article-title":"Predictive value of different thresholds of morning cortisol in diagnosing adrenal insufficiency","volume":"16","author":"Ghasham","year":"2024","journal-title":"Endocr. Metab. Sci."},{"key":"10.1016\/j.cca.2026.120909_bb0140","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline","volume":"101","author":"Bornstein","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.cca.2026.120909_bb0145","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/clinchem\/hvab056","article-title":"Method-specific cortisol and dexamethasone thresholds increase clinical specificity of the dexamethasone suppression test for Cushing syndrome","volume":"67","author":"Vogg","year":"2021","journal-title":"Clin. Chem."},{"key":"10.1016\/j.cca.2026.120909_bb0150","first-page":"1209","article-title":"Multi-steroid profiling by UHPLC-MS\/MS with post-column infusion of ammonium fluoride","volume":"15","author":"Schiffer","year":"2022","journal-title":"J. Chromatogr. B"},{"key":"10.1016\/j.cca.2026.120909_bb0155","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.contraception.2018.01.015","article-title":"Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS\/MS","volume":"97","author":"Blue","year":"2018","journal-title":"Contraception"},{"key":"10.1016\/j.cca.2026.120909_bb0160","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jchromb.2018.05.017","article-title":"Splitless hyphenation of SFC with MS by APCI, APPI, and ESI exemplified by steroids as model compounds","volume":"1091","author":"Parr","year":"2018","journal-title":"J. Chromatogr. B"}],"container-title":["Clinica Chimica Acta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009898126000914?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009898126000914?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:26:30Z","timestamp":1784017590000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009898126000914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":32,"alternative-id":["S0009898126000914"],"URL":"https:\/\/doi.org\/10.1016\/j.cca.2026.120909","relation":{},"ISSN":["0009-8981"],"issn-type":[{"value":"0009-8981","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Urinary free cortisol analyses: Enhancing their clinical performance in Cushing's syndrome management by means of LC-MS\/MS","name":"articletitle","label":"Article Title"},{"value":"Clinica Chimica Acta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cca.2026.120909","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"120909"}}