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

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.

• Authors: 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
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 10 Pg. 2801-2810 (09 28 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 35948272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

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

Topics

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