Succinate: A Serum Biomarker of SDHB-Mutated Paragangliomas and Pheochromocytomas

Constance Lamy, Hubert Tissot, Matthieu Faron, Eric Baudin, Livia Lamartina, Caroline Pradon, Abir Al Ghuzlan, Sophie Leboulleux, Jean Luc Perfettini, Angelo Paci, Julien Hadoux, Sophie Broutin

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    12 Citations (Scopus)

    Résumé

    Context: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that are frequently associated with succinate dehydrogenase (SDH) germline mutations. When mutated, SDH losses its function, thus leading to succinate accumulation. Objective: In this study, we evaluated serum succinate levels as a new metabolic biomarker in SDHx-related carriers. Methods: Retrospective monocentric study of 88 PPGL patients (43 sporadic, 35 SDHB, 10 SDHA/C/D), 17 tumor-free familial asymptomatic carriers (13 SDHB, 4 SDHC/D), and 60 healthy controls. Clinical, biological, and imaging data were reviewed. Serum succinate levels (n=280) were quantified by an ultra-performance liquid chromatography coupled to a tandem mass spectrometry method and correlated to SDHx mutational status, disease extension, and other biological biomarkers. Results: Serum succinate levels>7 μM allowed identification of tumor-free asymptomatic SDHB-mutated cases compared to a healthy control group (100% specificity; 85% sensitivity). At PPGL diagnosis, SDHB-mutated patients had a significantly increased median succinate level (14 μM) compared to sporadic patients (8 μM) (P<0.01). Metastatic disease extension was correlated to serum succinate levels (r=0.81). In the SDHB group, patients displaying highest tumor burdens showed significant increased succinate levels compared to the sporadic group (P<0.0001). Conclusions: In this pilot study, we showed that serum succinate level is an oncometabolic biomarker that should be useful to identify SDHB-related carriers. Succinate levels are also a marker of metabolic tumor burden in patients with a metastatic PPGL and a potential marker of treatment response and follow-up.

    langue originaleAnglais
    Pages (de - à)2801-2810
    Nombre de pages10
    journalJournal of Clinical Endocrinology and Metabolism
    Volume107
    Numéro de publication10
    Les DOIs
    étatPublié - 1 oct. 2022

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