Guido Di Dalmazi1,2, Marcus Quinkler3, Timo Deutschbein4, Cornelia Prehn5, Nada Rayes6, Matthias Kroiss7, Christina M Berr1, Günter Stalla8, Martin Fassnacht4,7, Jerzy Adamski5,9, Martin Reincke, Felix Beuschlein1,10. 1. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany. 2. Division of Endocrinology, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 3. Endocrinology in Charlottenburg, Berlin, Germany. 4. Division of Endocrinology/Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. 5. Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Munich, Germany. 6. Department of General-, Visceral and Transplant Surgery, Charité Campus Virchow Clinic, Berlin, Germany. 7. Central Laboratory, University Hospital Würzburg, Würzburg, Germany. 8. Max-Planck-Institute of Psychiatry, Clinical Neuroendocrinology Unit, München, Germany. 9. Lehrstuhl für Experimentelle Genetik, Technische Universität München, German Center for Diabetes Research (DZD), Neuherberg, Germany. 10. Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland.
Abstract
OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete β-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism.
OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS:Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabeticpatients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete β-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism.
Authors: Nadja S Sieber-Ruckstuhl; Bo Burla; Susanne Spoerel; Florence Schmid; Claudio Venzin; Amaury Cazenave-Gassiot; Anne K Bendt; Federico Torta; Markus R Wenk; Felicitas S Boretti Journal: Sci Rep Date: 2019-04-12 Impact factor: 4.379
Authors: Nadja S Sieber-Ruckstuhl; Wai Kin Tham; Franziska Baumgartner; Jeremy John Selva; Markus R Wenk; Bo Burla; Felicitas S Boretti Journal: Metabolites Date: 2022-03-30
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