{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:31:23Z","timestamp":1761611483268,"version":"3.37.3"},"reference-count":33,"publisher":"The Endocrine Society","issue":"11","funder":[{"name":"N\u00c3ocleo Regional do Centro da Liga Portuguesa Contra o Cancro"},{"name":"Funda\u00c3\u00a7\u00c3\u00a3o para a Ci\u00c3ancia e a Tecnologia","award":["SFRH\/BPD\/111100\/2015"],"award-info":[{"award-number":["SFRH\/BPD\/111100\/2015"]}]},{"name":"COMPETE2020 - POCI","award":["LISBOA-01-0145-FEDER-007660"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-007660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Metabolomic studies of pheochromocytoma and paraganglioma tissue showed a correlation between metabolomic profile and presence of SDHx mutations, especially a pronounced increase of succinate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare the metabolomic profile of 24-hour urine samples of SDHx mutation carriers with tumors (affected mutation carriers), without tumors (asymptomatic mutation carriers), and patients with sporadic pheochromocytomas and paragangliomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Proton nuclear magnetic resonance spectroscopic profiling of urine samples and metabolomic analysis using pairwise comparisons were complemented by metabolite set enrichment analysis to identify meaningful patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The urine of the affected SDHx carriers showed substantially lower levels of seven metabolites than the urine of asymptomatic mutation carriers (including, succinate and N-acetylaspartate). The urine of patients with SDHx-associated tumors presented substantially higher levels of three metabolites compared with the urine of patients without mutation; the metabolite set enrichment analysis identified gluconeogenesis, pyruvate, and aspartate metabolism as the pathways that most probably explained the differences found. N-acetylaspartate was the only metabolite the urinary levels of which were significantly different between the three groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The metabolomic urine profile of the SDHx mutation carriers with tumors is different from that of asymptomatic carriers and from that of patients with sporadic neoplasms. Differences are likely to reflect the altered mitochondria energy production and pseudohypoxia signature of these tumors. The urinary levels of N-acetylaspartate and succinate contrast with those reported in tumor tissue, suggesting a defective washout process of oncometabolites in association with tumorigenesis. The role of N-acetylaspartate as a tumor marker for these tumors merits further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2019-01101","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T16:48:57Z","timestamp":1563900537000},"page":"5467-5477","source":"Crossref","is-referenced-by-count":9,"title":["Metabolomic Urine Profile: Searching for New Biomarkers of SDHx-Associated Pheochromocytomas and Paragangliomas"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2786-3650","authenticated-orcid":false,"given":"Raquel G","family":"Martins","sequence":"first","affiliation":[{"name":"Endocrinology Department, Portuguese Oncology Institute of Coimbra, Coimbra, Portugal"},{"name":"Medical Psychology Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Oporto, Porto, Portugal"},{"name":"Research Centre, Portuguese Oncology Institute of Oporto, Porto, Portugal"}]},{"given":"Lu\u00eds G","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"ITQB NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Oeiras, Portugal"}]},{"given":"Nuno","family":"Cunha","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Department, Portuguese Oncology Institute of Coimbra, Coimbra, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Bugalho","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes and Metabolism Department, CHULN-Hospital Santa Maria, Lisbon, Portugal"},{"name":"Faculty of Medicine, University of Lisbon, Lisbon, Portugal"}]}],"member":"80","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"issue":"2","key":"2019100411063498600_bib1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrendo.2014.188","article-title":"Paraganglioma and phaeochromocytoma: from genetics to personalized 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