{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:53:58Z","timestamp":1793012038795,"version":"4.5.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Institut de Biochimie & Biologie Mol\u00e9culaire"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Pheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate\/fumarate ratio (RS\/F) than non-SDHx\u2013mutated ones. Also, an increase in serum succinate levels has been reported in patients with germline SDHB or SDHD PV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess whether measurement of serum succinate, fumarate levels, and RS\/F might aid identification of an SDHx germline PV\/likely pathogenic variant (LPV) in patients with PPGL or in asymptomatic relatives; and to guide identification of a PV\/LPV among the variants of unknown significance (VUS) identified in SDHx by next-generation sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This prospective monocentric study included 93 patients attending an endocrine oncogenetic unit for genetic testing. Succinate and fumarate were measured in serum by gas chromatography coupled to mass spectrometry. The RS\/F was calculated to assess SDH enzymatic function. Diagnostic performance was assessed by receiver operating characteristic analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>RS\/F had a higher discriminant power than succinate alone to identify an SDHx PV\/LPV in patients with PPGL. However, SDHD PVs\/LPVs are frequently missed. Only RS\/F differed between asymptomatic SDHB\/SDHD PV\/LPV carriers and SDHB\/SDHD-linked patients with PPGL. Finally RS\/F could be helpful to easily evaluate the functional impact of VUS in SDHx.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Measurement of serum RS\/F in patients with PPGL and in asymptomatic relatives is a valuable initial workup tool to detect those carrying a germline PV\/LPV in SDHx. Its discriminative power is equal or superior to those of succinate measured alone. SDHD PVs\/LPVs are less frequently identified by these biochemical tools. Use of RS\/F for SDHx VUS reclassification needs to be evaluated further.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad109","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T16:40:15Z","timestamp":1677516015000},"page":"2343-2352","source":"Crossref","is-referenced-by-count":11,"title":["Serum Succinate\/Fumarate Ratio in Patients With Paraganglioma\/Pheochromocytoma Attending an Endocrine Oncogenetic Unit"],"prefix":"10.1210","volume":"108","author":[{"given":"L\u00e9o-Paul","family":"Bancel","sequence":"first","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Masso","sequence":"additional","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Frederique","family":"Dessein","sequence":"additional","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Aubert","sequence":"additional","affiliation":[{"name":"CHU Lille, Service d\u2019Anatomie Pathologique, Centre de Biologie Pathologie , F-59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Leteurtre","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity, Plasticity and Resistance to therapies , F-59000 Lille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Coppin","sequence":"additional","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Fran\u00e7oise","family":"Odou","sequence":"additional","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Do","family":"Cao","sequence":"additional","affiliation":[{"name":"CHU Lille, Service d\u2019Endocrinologie, Diab\u00e9tologie, M\u00e9tabolisme, Nutrition, H\u00f4pital Claude Huriez , F-59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Cardot-Bauters","sequence":"additional","affiliation":[{"name":"CHU Lille, Service d\u2019Endocrinologie, Diab\u00e9tologie, M\u00e9tabolisme, Nutrition, H\u00f4pital Claude Huriez , F-59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-4487","authenticated-orcid":false,"given":"Pascal","family":"Pigny","sequence":"additional","affiliation":[{"name":"CHU Lille, Laboratoire de Biochimie-Hormonologie, M\u00e9tabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie , F.59037 Lille Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"issue":"5","key":"2023081819555165000_dgad109-B1","first-page":"552","article-title":"Mitochondrial complex II, a novel target for anti-cancer agents","volume":"1827","author":"Kluckova","year":"2013","journal-title":"Biochem Biophys Acta"},{"issue":"6","key":"2023081819555165000_dgad109-B2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/jmedgenet-2017-105127","article-title":"Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD","volume":"55","author":"Andrews","year":"2018","journal-title":"J Med Genet"},{"issue":"3","key":"2023081819555165000_dgad109-B3","doi-asserted-by":"crossref","first-page":"e1301","DOI":"10.1210\/clinem\/dgaa888","article-title":"Screening of a large cohort of asymptomatic SDHx mutation carriers in routine practice","volume":"106","author":"Saie","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2023081819555165000_dgad109-B4","doi-asserted-by":"crossref","first-page":"e1907","DOI":"10.1210\/clinem\/dgac019","article-title":"Surveillance improves outcomes for carriers of SDHB pathogenic variants: a multicenter study","volume":"107","author":"Davidoff","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2023081819555165000_dgad109-B5","article-title":"Emerging considerations on mitochondrial and cytosolic metabolic features in SDH-deficient cancer cells","volume":"26","author":"Vamecq","year":"2021","journal-title":"Mol Genet Metab Rep"},{"issue":"10","key":"2023081819555165000_dgad109-B6","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1210\/jc.2014-2151","article-title":"Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas\/paragangliomas due to succinate dehydrogenase deficiency","volume":"99","author":"Richter","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"20","key":"2023081819555165000_dgad109-B7","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.1158\/1078-0432.CCR-16-2250","article-title":"Targeted exome sequencing of Krebs cycle genes reveals candidate cancer-predisposing mutations in pheochromocytomas and paragangliomas","volume":"23","author":"Remacha","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"1","key":"2023081819555165000_dgad109-B8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1210\/en.2013-1549","article-title":"Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB\/D-related paraganglioma: initial experimental and ex vivo findings","volume":"155","author":"Lendvai","year":"2014","journal-title":"Endocrinology"},{"issue":"9","key":"2023081819555165000_dgad109-B9","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110453","article-title":"SDHB Knockout and succinate accumulation are insufficient for tumorigenesis but dual SDHB\/NF1 loss yields SDHx-like pheochromocytomas","volume":"38","author":"Armstrong","year":"2022","journal-title":"Cell Rep"},{"issue":"3","key":"2023081819555165000_dgad109-B10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41436-018-0106-5","article-title":"Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma","volume":"21","author":"Richter","year":"2019","journal-title":"Genet Med"},{"issue":"6","key":"2023081819555165000_dgad109-B11","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/gim.2011.63","article-title":"Elevated plasma succinate in PTEN, SDHB, and SDHD mutation-positive individuals","volume":"14","author":"Hobert J","year":"2012","journal-title":"Genet Med"},{"issue":"10","key":"2023081819555165000_dgad109-B12","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1210\/clinem\/dgac474","article-title":"Succinate: a serum biomarker of SDHB mutated paragangliomas and pheochromocytomas","volume":"107","author":"Lamy","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2023081819555165000_dgad109-B13","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1530\/EC-20-0460","article-title":"Genetic predisposition to neural crest-derived tumors: revisiting the role of KIF1B","volume":"9","author":"Cardot Bauters","year":"2020","journal-title":"Endocr Connect"},{"issue":"5","key":"2023081819555165000_dgad109-B14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"3","key":"2023081819555165000_dgad109-B15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under 2 or more correlated ROC curves: a non parametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"2023081819555165000_dgad109-B16","author":"Bancel"},{"issue":"2","key":"2023081819555165000_dgad109-B17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/his.14681","article-title":"An exploration in pitfalls in interpreting SDHB immunohistochemistry","volume":"81","author":"Ding","year":"2022","journal-title":"Histopathology"},{"issue":"21","key":"2023081819555165000_dgad109-B18","doi-asserted-by":"crossref","first-page":"6733","DOI":"10.1158\/1078-0432.CCR-17-1397","article-title":"Biochemical, molecular, and clinical characterization of succinate dehydrogenase subunit A variants of unknown significance","volume":"23","author":"Bannon","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"1","key":"2023081819555165000_dgad109-B19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/ajmg.a.37986","article-title":"SDHA Mutation with dominant transmission results in complex II deficiency with ocular, cardiac, and neurological involvement","volume":"173A","author":"Courage","year":"2017","journal-title":"Am J Med Genet"},{"issue":"2","key":"2023081819555165000_dgad109-B20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/PAS.0b013e3182671178","article-title":"Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation","volume":"37","author":"Miettinen","year":"2013","journal-title":"Am J Surg Pathol"},{"issue":"4","key":"2023081819555165000_dgad109-B21","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.eprac.2020.09.011","article-title":"Chromogranin A in a cohort of pheochromocytomas and paragangliomas: usefulness at diagnosis and as early biomarker of recurrence","volume":"27","author":"Parisien-La Salle","year":"2021","journal-title":"Endocr Pract"},{"issue":"4","key":"2023081819555165000_dgad109-B22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1530\/ERC-21-0359","article-title":"Head\/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine","volume":"29","author":"Richter","year":"2022","journal-title":"Endocr Relat Cancer"},{"issue":"12","key":"2023081819555165000_dgad109-B23","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1158\/2159-8290.CD-20-0844","article-title":"Targeting metabolic plasticity and flexibility dynamics for cancer therapy","volume":"10","author":"Fendt","year":"2020","journal-title":"Cancer Discov"},{"issue":"4","key":"2023081819555165000_dgad109-B24","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1093\/cvr\/cvaa148","article-title":"Mechanism of succinate efflux upon reperfusion of the ischaemic heart","volume":"117","author":"Prag","year":"2021","journal-title":"Cardiovasc Res"},{"issue":"4","key":"2023081819555165000_dgad109-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/iovs.63.4.1","article-title":"Monocarboxylate transporter 1 (MCT1) mediates succinate export in the retina","volume":"63","author":"Bisbach","year":"2022","journal-title":"Invest Ophtalmol Vis Sci"},{"issue":"2","key":"2023081819555165000_dgad109-B26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/jmedgenet-2019-106214","article-title":"Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked pheochromocytoma-paraganglioma","volume":"57","author":"Bayley","year":"2020","journal-title":"J Med Genet"},{"issue":"13","key":"2023081819555165000_dgad109-B27","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1158\/0008-5472.CAN-20-2936","article-title":"Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress, and sensitivity to ascorbate","volume":"81","author":"Goncalves","year":"2021","journal-title":"Cancer Res"},{"key":"2023081819555165000_dgad109-B28","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.biochi.2022.07.008","article-title":"Serum fatty acid profiling in patients with SDHx mutations: new advances on cellular metabolism in SDH deficiency","volume":"201","author":"Vamecq","year":"2022","journal-title":"Biochimie"},{"issue":"1","key":"2023081819555165000_dgad109-B29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.gim.2021.08.004","article-title":"Quantifying evidence toward pathogenicity for rare phenotypes: the case of succinate dehydrogenase genes, SDHB and SDHD","volume":"24","author":"Garrett","year":"2022","journal-title":"Genet Med"},{"issue":"6","key":"2023081819555165000_dgad109-B30","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1007\/s00259-019-04633-9","article-title":"Succinate detection using in vivo 1H-MR spectroscopy identifies germline and somatic SDHx mutation in paragangliomas","volume":"47","author":"Lussey-Lepoutre","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2023081819555165000_dgad109-B31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ymgmr.2016.12.006","article-title":"Utility of the succinate:fumarate ratio for assessing SDH dysfunction in different tumor types","volume":"10","author":"Kim","year":"2017","journal-title":"Mol Genet Metab Rep"},{"issue":"5","key":"2023081819555165000_dgad109-B32","doi-asserted-by":"crossref","first-page":"e1937","DOI":"10.1210\/clinem\/dgaa982","article-title":"Metastatic pheochromocytomas and abdominal paragangliomas","volume":"106","author":"Grandberg","year":"2021","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad109\/49568699\/dgad109.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/9\/2343\/51171955\/dgad109.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/9\/2343\/51171955\/dgad109.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T20:02:20Z","timestamp":1692388940000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/9\/2343\/7059023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,2,27]]},"published-print":{"date-parts":[[2023,8,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad109","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,2,27]]}}}