{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T17:19:47Z","timestamp":1783963187429,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["20ZR1434100"],"award-info":[{"award-number":["20ZR1434100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Hypopituitarism (Hypo-Pit) is partial or complete insufficiency of anterior pituitary hormones. Besides hormone metabolism, the global metabolomics in Hypo-Pit are largely unknown. We aimed to explore potential biomarkers to aid in diagnosis and personalized treatment.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Using both univariate and multivariate statistical methods, we identified 72 differentially abundant features through liquid chromatography coupled to high-resolution mass spectrometry, obtained in 134 males with Hypo-Pit and 90 age matched healthy controls.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Hypopituitarism exhibits an increased abundance of metabolites involved in amino acid degradation and glycerophospholipid synthesis, but decreased content of metabolites in steroid hormone synthesis and fatty acid beta-oxidation. Significantly changed metabolites included creatine, creatinine, L-alanine, phosphocholines, androstenedione, hydroprenenolone, and acylcarnitines. In Hypo-Pit patients, the increased ratio of creatine\/creatinine suggested reduced creatine uptake and impaired creatine utilization, whereas the decreased level of beta-hydroxybutyrate, acetylcarnitine (C2) and a significantly decreased ratio of decanoylcarnitine (C10) to free carnitine suggested an impaired beta-oxidation. Furthermore, the creatine\/creatinine and decanoylcarnitine\/carnitine ratio were identified as diagnostic biomarkers for Hypo-Pit with AUCs of 0.976 and 0.988, respectively. Finally, we found that the creatinine and decanoylcarnitine\/carnitine ratio could distinguish cases that were sensitive vs. resistant to human chorionic gonadotropin therapy.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We provided a global picture of altered metabolic pathways in Hypo-Pit, and the identified biomarkers in creatine metabolism and beta-oxidation might be useful for the preliminary screening and diagnosis of Hypo-Pit.<\/jats:p>","DOI":"10.3389\/fphar.2021.684869","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T06:44:39Z","timestamp":1625726679000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Untargeted LC\/MS-Based Metabolic Phenotyping of Hypopituitarism in Young Males"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuwen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouyue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuqian","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s11102-006-0416-5","article-title":"Hypopituitarism","volume":"9","author":"Ascoli","year":"2006","journal-title":"Pituitary"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5152029","DOI":"10.1155\/2016\/5152029","article-title":"Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity","volume":"2016","author":"Barbieri","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1042\/bj2580677","article-title":"Regulation of Carnitine Palmitoyltransferase In Vivo by Glucagon and Insulin","volume":"258","author":"Brady","year":"1989","journal-title":"Biochem. 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