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Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 11 serum steroids in adrenal CS (<jats:italic>n<\/jats:italic>\u00a0=\u00a013) and CD (<jats:italic>n<\/jats:italic>\u00a0=\u00a015) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS\/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with <jats:italic>t<\/jats:italic>-tests. The sensitivity and specificity of DHEA-S ratios\u00a0&amp;lt;0.40 were 92.31% (95% CI 64.0%\u201399.8%) and 93.33% (95% CI 68.1%\u201399.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios\u00a0&amp;lt;0.18 were 100% (95% CI 75.3%\u2013100.0%) and 100% (95% CI 78.2%\u2013100.0%), respectively, in identifying adrenal CS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1158573","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T05:35:54Z","timestamp":1684215354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Chang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/003655102753517181","article-title":"Single determination of plasma ACTH using an immunoradiometric assay with high detectability differentiates between ACTH-dependent and -independent cushing's syndrome","volume":"62","author":"Klose","year":"2002","journal-title":"Scandinavian J Clin Lab Invest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030871","article-title":"Diagnosis and complications of cushing's syndrome: a consensus statement","volume":"88","author":"Arnaldi","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0962","article-title":"Assessment of ACTH assay variability: a multicenter study","volume":"164","author":"Pecori Giraldi","year":"2011","journal-title":"Eur J endocrinology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3803\/EnM.2015.30.3.297","article-title":"Limited diagnostic utility of plasma adrenocorticotropic hormone for differentiation between adrenal cushing syndrome and cushing disease","volume":"30","author":"Hong","year":"2015","journal-title":"Endocrinol Metab (Seoul Korea)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/js.2019-00027","article-title":"Assay-specific spurious ACTH results lead to misdiagnosis, unnecessary testing, and surgical misadventure-a case series","volume":"3","author":"Greene","year":"2019","journal-title":"J Endocrine Society"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-018-0770-x","article-title":"Heterophile antibody to adrenocorticotropin hormone interfering with the investigation of cushing's syndrome","volume":"34","author":"Morton","year":"2019","journal-title":"Indian J Clin Biochem IJCB"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.282582","article-title":"Plasma steroid metabolome profiling for diagnosis and subtyping patients with cushing syndrome","volume":"64","author":"Eisenhofer","year":"2018","journal-title":"Clin Chem"},{"key":"B8","article-title":"The diagnosis of cushing's syndrome: an endocrine society clinical practice guideline","volume":"29","author":"Gilbert","year":"2008","journal-title":"Clin biochemist Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.05.002","article-title":"Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS\/MS: impact of gender, age, oral contraceptives, body mass index and blood pressure status","volume":"470","author":"Eisenhofer","year":"2017","journal-title":"Clinica chimica acta; 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