Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

Di Dalmazi, Guido; Quinkler, Marcus; Deutschbein, Timo; Prehn, Cornelia; Rayes, Nada; Kroiss, Matthias; Berr, Christina M; Stalla, Günter; Fassnacht, Martin; Adamski, Jerzy; Reincke, Martin; Beuschlein, Felix

doi:10.1530/eje-17-0109

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Journal article

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

Di Dalmazi, Guido 9Division of Endocrinology, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Quinkler, Marcus 2Endocrinology in Charlottenburg, Berlin, Germany
Deutschbein, Timo 3Division of Endocrinology/Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
Prehn, Cornelia 4Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Munich, Germany
Rayes, Nada 5Department of General-, Visceral and Transplant Surgery, Charité Campus Virchow Clinic, Berlin, Germany
Kroiss, Matthias 6Central Laboratory, University Hospital Würzburg, Würzburg, Germany
Berr, Christina M 1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
Stalla, Günter 7Max-Planck-Institute of Psychiatry, Clinical Neuroendocrinology Unit, München, Germany
Fassnacht, Martin 6Central Laboratory, University Hospital Würzburg, Würzburg, Germany
Adamski, Jerzy 8Lehrstuhl für Experimentelle Genetik, Technische Universität München, German Center for Diabetes Research (DZD), Neuherberg, Germany
Reincke, Martin
Beuschlein, Felix 10Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland

Published in:

European Journal of Endocrinology. - Bioscientifica. - 2017, vol. 177, no. 2, p. 227-237

Endocrinology, Diabetes and Metabolism

English
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.

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