{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:43:06Z","timestamp":1791434586064,"version":"4.3.3"},"reference-count":50,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2021.11"],"award-info":[{"award-number":["DKS 2021.11"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2024.16)"],"award-info":[{"award-number":["DKS 2024.16)"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021729","name":"Mitteldeutsche Kinderkrebsforschung and Medical Faculty, University of Augsburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Adrenocortical tumors (ACTs) comprise adrenocortical adenomas (ACAs) and adrenocortical carcinomas (ACCs); the latter are highly aggressive. Pediatric adrenocortical tumors (pACTs) are functional and thus symptomatic. We investigated whether gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis can detect tumors and di\ufb00erentiate between adenomas and carcinomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We investigated 46 patients with pACTs (age: median 6.9; range 0.7-17 years; 36 females; 21 ACAs, 25 ACCs) from the German Society for Pediatric Oncology and Hematology for Malignant Endocrine Tumors study at the time of initial diagnosis. Thirty-six urinary C21-, C19-, and C18-steroid metabolites were quanti\ufb01ed from spot urines by targeted GC-MS. Data underwent computational analysis by log transformation followed by z-transformation and machine learning classifiers, such as cluster and principal component analysis, logistic regression, and decision trees.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>pACTs and controls showed highly significant differences (P &amp;lt; .001) for most parameters, particularly gross elevation of the urinary metabolites of the \u03945-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone, as well as of tetrahydro-11-deoxycortisol (THS), the urinary main metabolite of 11-deoxycortisol. Pediatric adrenocortical carcinomas (pACCs) showed higher THS and decreased corticosterone metabolites (P &amp;lt; .05). Selected biomarkers discriminated pACTs from controls, as well as pACCs from pediatric adrenocortical adenomas (pACAs) with high sensitivity and specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Urinary GC-MS steroid metabolome analysis is noninvasive and allows good detection of ACTs from spot urine as well as good differentiation of pACCs from pACAs. The dominance of \u03945-steroids in pACTs points to the zona reticularis as a common site of origin. The parameters differentiating pACAs from pACCs differ from adults.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf613","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:57:54Z","timestamp":1762865874000},"page":"1337-1347","source":"Crossref","is-referenced-by-count":4,"title":["Delineating Pediatric Adrenocortical Tumors by GC-MS Urinary Steroid Metabolome Analysis: Observations From the MET Study"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-5957","authenticated-orcid":false,"given":"Stefan A","family":"Wudy","sequence":"first","affiliation":[{"name":"Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormonal Analytics, Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University Giessen , Giessen D-35392 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joern","family":"Pons-K\u00fchnemann","sequence":"additional","affiliation":[{"name":"Medical Statistics, Institute of Medical Informatics, Justus Liebig University Giessen , Giessen D-35392 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-4045","authenticated-orcid":false,"given":"Marina","family":"Kunstreich","sequence":"additional","affiliation":[{"name":"Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg , Augsburg 86156 ,","place":["Germany"]},{"name":"Department of Pediatrics, Pediatric Hematology\/Oncology, Otto-von-Guericke-University , Magdeburg 39120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1732-1869","authenticated-orcid":false,"given":"Antje","family":"Redlich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Hematology\/Oncology, Otto-von-Guericke-University , Magdeburg 39120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela F","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormonal Analytics, Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University Giessen , Giessen D-35392 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-0503","authenticated-orcid":false,"given":"Michaela","family":"Kuhlen","sequence":"additional","affiliation":[{"name":"Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg , Augsburg 86156 ,","place":["Germany"]},{"name":"Bavarian Cancer Research Center (BZKF) , Augsburg 86156 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"issue":"5","key":"2026042119570652800_dgaf613-B1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1200\/JCO.2004.08.085","article-title":"Clinical and outcome characteristics of children with adrenocortical tumors: a report from the international pediatric adrenocortical tumor registry","volume":"22","author":"Michalkiewicz","year":"2004","journal-title":"J Clin Oncol"},{"issue":"3","key":"2026042119570652800_dgaf613-B2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1515\/jpem-2016-0080","article-title":"Adrenocortical neoplasms in adulthood and childhood: distinct presentation. 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