Journalartikel

Jahr der Veröffentlichung: 2024

Zeitschrift: EBioMedicine

Bandnummer: 99

ISSN: 2352-3964

Open Access Status: Green

DOI Link: https://doi.org/10.1016/j.ebiom.2023.104907

Verlag: Elsevier

Abstract: 
Background Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS.Methods We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female).Findings Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(110-OH-An + 110-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%.Interpretation GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes.

Harvard-Zitierstil: Braun, L., Osswald, A., Zopp, S., Rubinstein, G., Vogel, F., Riester, A., et al. (2024) Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping, EBioMedicine, 99, Article 104907. https://doi.org/10.1016/j.ebiom.2023.104907

APA-Zitierstil: Braun, L., Osswald, A., Zopp, S., Rubinstein, G., Vogel, F., Riester, A., Honegger, J., Eisenhofer, G., Constantinescu, G., Deutschbein, T., Quinkler, M., Elbelt, U., Kuenzel, H., Nowotny, H., Reisch, N., Hartmann, M., Beuschlein, F., Pons-Kuehnemann, J., Reincke, M., ...Wudy, S. (2024). Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping. EBioMedicine. 99, Article 104907. https://doi.org/10.1016/j.ebiom.2023.104907