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

J Clin Endocrinol Metab. 2022 Sep 28;107(10):2801-2810. doi: 10.1210/clinem/dgac474.

Abstract

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.

Keywords: SDH; biomarker; paraganglioma; pheochromocytoma; succinate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms* / diagnosis
  • Adrenal Gland Neoplasms* / genetics
  • Adrenal Gland Neoplasms* / metabolism
  • Biomarkers, Tumor / genetics
  • Germ-Line Mutation
  • Humans
  • Mutation
  • Paraganglioma* / diagnosis
  • Paraganglioma* / genetics
  • Paraganglioma* / pathology
  • Pheochromocytoma* / diagnosis
  • Pheochromocytoma* / genetics
  • Pheochromocytoma* / pathology
  • Pilot Projects
  • Retrospective Studies
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism
  • Succinic Acid / metabolism

Substances

  • Biomarkers, Tumor
  • Succinic Acid
  • SDHB protein, human
  • Succinate Dehydrogenase