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Endocrine Abstracts (2016) 41 GP29 | DOI: 10.1530/endoabs.41.GP29

1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; 2Endocrinology in Charlottenburg, Berlin, Germany; 3Department of General-, Visceral and Transplant Surgery, Charité Campus Virchow Clinic, Berlin, Germany; 4Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany; 5Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Munich, Germany; 6Max-Planck-Institute of Psychiatry, Clinical Neuroendocrinology Unit, Munich, Germany.


Background: Cushing’s syndrome (CS) is a chronic disorder characterized by endogenous cortisol excess resulting in long-term metabolic and cardiovascular consequences. The identification of metabolic alterations related to hypercortisolism could be beneficial in tailoring treatments of co-morbidities. Our aim was to characterize the metabolic alterations of patients with hypercortisolism by targeted plasma metabolomic profiling.

Methods: Subjects (n=149) were recruited from three German centers (Munich, Berlin, and Würzburg) belonging to the German Cushing registry (CUSTODES) and the European Network for the Study of Adrenal Tumors (ENSAT). According to clinical and hormonal characteristics, four groups were identified: non-secreting adrenocortical adenomas (NS) (n=27), subclinical hypercortisolism (SH) (n=34), CS (n=46), and patients in whom CS has been excluded (EC) (n=42). Plasma targeted metabolomics profiling was performed using the mass spectrometry-based kit AbsoluteIDQ-p180 (BIOCRATES AG, Austria).

Results: Metabolic profile of patients with CS was characterized by reduced carnitine and acetyl-carnitine levels, with respect to EC. Polyamine levels were increased in CS patients, whereas several glucogenic amino acids were decreased, when compared to EC. Similar alterations were also identified in SH patients. Spermidine was progressively increased among NS, SH, and CS patients, and showed positive correlation with post-DST cortisol (Coefficient=0.341, P<0.001). Serotonin levels were increased in adrenal-dependent hypercortisolism (SH and CS), when compared to EC, NS, and ACTH-dependent CS. Logistic regression analysis showed that the panel of significant metabolites among groups was able to correctly classify 83.8% of the patients. Three scores were identified from logistic regression that showed good accuracy in discriminating CS vs. EC, CS vs SH, and SH vs NS (sensitivity/specificity of 87%/83%, 89%/88%, and 78%/74%, respectively).

Conclusion: Metabolomic profiling revealed the presence of several disturbances in patients with hypercortisolism, mainly involving polyamine and amino acids metabolism, and β-oxidation. Metabolomic analysis showed also good accuracy in classifying patients with hypercortisolism according to their specific metabolic profile. Further studies are currently ongoing to analyze a large cohort of matched normal control subjects.

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