Serum Succinate/Fumarate Ratio in Patients With Paraganglioma/Pheochromocytoma Attending an Endocrine Oncogenetic Unit.

Autor:	Bancel LP; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France., Masso V; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France., Dessein AF; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France., Aubert S; CHU Lille, Service d'Anatomie Pathologique, Centre de Biologie Pathologie, F-59037 Lille Cedex, France., Leteurtre E; University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity, Plasticity and Resistance to therapies, F-59000 Lille, France., Coppin L; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France., Odou MF; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France., Cao CD; CHU Lille, Service d'Endocrinologie, Diabétologie, Métabolisme, Nutrition, Hôpital Claude Huriez, F-59037 Lille Cedex, France., Cardot-Bauters C; CHU Lille, Service d'Endocrinologie, Diabétologie, Métabolisme, Nutrition, Hôpital Claude Huriez, F-59037 Lille Cedex, France., Pigny P; CHU Lille, Laboratoire de Biochimie-Hormonologie, Métabolisme, Nutrition, Oncologie, Centre de Biologie Pathologie, F.59037 Lille Cedex, France.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2023 Aug 18; Vol. 108 (9), pp. 2343-2352.
DOI:	10.1210/clinem/dgad109
Abstrakt:	Context: Pheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate/fumarate ratio (RS/F) than non-SDHx-mutated ones. Also, an increase in serum succinate levels has been reported in patients with germline SDHB or SDHD PV. Objective: 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. Methods: 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. Results: 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. Conclusion: 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. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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