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Metabolic impact of pheochromocytoma/paraganglioma: Targeted metabolomics in patients before and after tumor removal


Erlic, Zoran; Kurlbaum, Max; Deutschbein, Timo; Nölting, Svenja; Prejbisz, Aleksander; Timmers, Henri J; Richter, Susan; Prehn, Cornelia; Weismann, Dirk; Adamski, Jerzy; Januszewicz, Andrzej; Reincke, Martin; Fassnacht, Martin; Robledo, Mercedes; Eisenhofer, Graeme; Beuschlein, Felix; Kroiss, Matthias (2019). Metabolic impact of pheochromocytoma/paraganglioma: Targeted metabolomics in patients before and after tumor removal. European Journal of Endocrinology, 181(6):647-657.

Abstract

Objective: Excess catecholamine release by pheochromocytomas and paragangliomas (PPGL) leads to characteristic clinical features and increased morbidity and mortality. The influence of PPGLs on metabolism is ill described but may impact diagnosis and management. The objective of this study was to systematically and quantitatively study PPGL induced metabolic changes at a systems level.
Design: Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens in a clinically well characterized prospective cohort study.
Methods: Analyses of metabolic profiles of plasma specimens from 56 prospectively enrolled and clinically well characterized patients (23 males, 33 females) with catecholamine-producing PPGL before and after surgery, as well as measurement of 24h-urinary catecholamine using LC-MS/MS.
Results: From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: 5 amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and 1 glycerophospholipid (PCaeC34:2) with increased concentrations and 6 glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), 2 sphingomyelins (SMC24:1, SMC26:1) and hexose with decreased levels after surgery. Patients with a noradrenergic tumor phenotype had more pronounced alterations compared to those with an adrenergic tumor phenotype. Weak, but significant correlations for 8 of these 15 metabolites with total urine catecholamine levels were identified.
Conclusions: This first large prospective metabolomics analysis of PPGL patients demonstrates broad metabolic consequences of catecholamine excess. Robust impact on lipid and amino acid metabolism may contribute to increased morbidity of PPGL patients.

Abstract

Objective: Excess catecholamine release by pheochromocytomas and paragangliomas (PPGL) leads to characteristic clinical features and increased morbidity and mortality. The influence of PPGLs on metabolism is ill described but may impact diagnosis and management. The objective of this study was to systematically and quantitatively study PPGL induced metabolic changes at a systems level.
Design: Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens in a clinically well characterized prospective cohort study.
Methods: Analyses of metabolic profiles of plasma specimens from 56 prospectively enrolled and clinically well characterized patients (23 males, 33 females) with catecholamine-producing PPGL before and after surgery, as well as measurement of 24h-urinary catecholamine using LC-MS/MS.
Results: From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: 5 amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and 1 glycerophospholipid (PCaeC34:2) with increased concentrations and 6 glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), 2 sphingomyelins (SMC24:1, SMC26:1) and hexose with decreased levels after surgery. Patients with a noradrenergic tumor phenotype had more pronounced alterations compared to those with an adrenergic tumor phenotype. Weak, but significant correlations for 8 of these 15 metabolites with total urine catecholamine levels were identified.
Conclusions: This first large prospective metabolomics analysis of PPGL patients demonstrates broad metabolic consequences of catecholamine excess. Robust impact on lipid and amino acid metabolism may contribute to increased morbidity of PPGL patients.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:320 Political science
330 Economics
Language:English
Date:1 December 2019
Deposited On:25 Mar 2019 13:04
Last Modified:03 Mar 2020 12:07
Publisher:BioScientifica Ltd.
ISSN:0804-4643
Additional Information:This is not the definitive version of record of this article. This manuscript has been accepted for publication in European Journal of Endocrinology, but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the journal accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at https://doi.org/10.1530/EJE-19-0589 European Society of Endocrinology, 2019
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1530/EJE-19-0589

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