Zoran Erlic1, Max Kurlbaum2,3, Timo Deutschbein3, Svenja Nölting4, Aleksander Prejbisz5, Henri Timmers6, Susan Richter7, Cornelia Prehn8, Dirk Weismann3, Jerzy Adamski8,9,10,11, Andrzej Januszewicz5, Martin Reincke4, Martin Fassnacht2,3,12, Mercedes Robledo13, Graeme Eisenhofer7, Felix Beuschlein1,4, Matthias Kroiss2,3,12. 1. Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland. 2. Core Unit Clinical Mass Spectrometry, University Hospital Würzburg, Würzburg, Germany. 3. Division of Endocrinology and Diabetology, Department of Internal Medicine I, Universitätsklinikum Würzburg, Würzburg, Germany. 4. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany. 5. Department of Hypertension, Institute of Cardiology, Warsaw, Poland. 6. Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. 7. Institut für Klinische Chemie und Labormedizin, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. 8. Helmholtz Zentrum München, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany. 9. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 10. Chair for Experimental Genetics, Technical University of Munich, Freising-Weihenstephan, Germany. 11. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 12. Comprehensive Cancer Center Mainfranken, Universität Würzburg, Würzburg, Germany. 13. Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
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 24-h urinary catecholamine using LC-MS/MS. RESULTS: From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: five amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and one glycerophospholipid (PCaeC34:2) with increased concentrations and six glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), two 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.
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 24-h urinary catecholamine using LC-MS/MS. RESULTS: From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: five amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and one glycerophospholipid (PCaeC34:2) with increased concentrations and six glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), two 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.
Authors: Lauren N Krumeich; Andrew J Cucchiara; Katherine L Nathanson; Rachel R Kelz; Lauren Fishbein; Douglas L Fraker; Robert E Roses; Debbie L Cohen; Heather Wachtel Journal: J Clin Endocrinol Metab Date: 2021-09-27 Impact factor: 6.134
Authors: Nikolaos G Bliziotis; Leo A J Kluijtmans; Sebastian Soto; Gerjen H Tinnevelt; Katharina Langton; Mercedes Robledo; Christina Pamporaki; Udo F H Engelke; Zoran Erlic; Jasper Engel; Timo Deutschbein; Svenja Nölting; Aleksander Prejbisz; Susan Richter; Cornelia Prehn; Jerzy Adamski; Andrzej Januszewicz; Martin Reincke; Martin Fassnacht; Graeme Eisenhofer; Felix Beuschlein; Matthias Kroiss; Ron A Wevers; Jeroen J Jansen; Jaap Deinum; Henri J L M Timmers Journal: Endocrine Date: 2021-09-18 Impact factor: 3.633
Authors: Smarti Reel; Parminder S Reel; Zoran Erlic; Laurence Amar; Alessio Pecori; Casper K Larsen; Martina Tetti; Christina Pamporaki; Cornelia Prehn; Jerzy Adamski; Aleksander Prejbisz; Filippo Ceccato; Carla Scaroni; Matthias Kroiss; Michael C Dennedy; Jaap Deinum; Graeme Eisenhofer; Katharina Langton; Paolo Mulatero; Martin Reincke; Gian Paolo Rossi; Livia Lenzini; Eleanor Davies; Anne-Paule Gimenez-Roqueplo; Guillaume Assié; Anne Blanchard; Maria-Christina Zennaro; Felix Beuschlein; Emily R Jefferson Journal: Metabolites Date: 2022-08-16