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

Erlic, Zoran; Kurlbaum, Max; Deutschbein, Timo; Noelting, 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 und Kroiss, Matthias (2019): Metabolic impact of pheochromocytoma/paraganglioma: targeted metabolomics in patients before and after tumor removal. In: European Journal of Endocrinology, Bd. 181, Nr. 6: S. 647-657

Abstract

Objective: Excess catecholamine release by pheochromocytomas and paragang liomas (PPGL) leads to characteristic clinical features and increased morbidity and mortality. The in fluence 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 catecholamin e-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0804-4643
• Sprache: Englisch