Academic Journal
Delineating endogenous Cushing’s syndrome by GC-MS urinary steroid metabotypingResearch in context
| العنوان: | Delineating endogenous Cushing’s syndrome by GC-MS urinary steroid metabotypingResearch in context |
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| المؤلفون: | Leah T. Braun, Andrea Osswald, Stephanie Zopp, German Rubinstein, Frederick Vogel, Anna Riester, Jürgen Honegger, Graeme Eisenhofer, Georgiana Constantinescu, Timo Deutschbein, Marcus Quinkler, Ulf Elbelt, Heike Künzel, Hanna F. Nowotny, Nicole Reisch, Michaela F. Hartmann, Felix Beuschlein, Jörn Pons-Kühnemann, Martin Reincke, Stefan A. Wudy |
| المصدر: | EBioMedicine, Vol 99, Iss , Pp 104907- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Medicine (General) |
| مصطلحات موضوعية: | Cushing’s disease, Steroid profiling, Hypercortisolism, GC-MS analysis, Medicine, Medicine (General), R5-920 |
| الوصف: | Summary: 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)/(11β-OH-An + 11β-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. Funding: The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352396423004735; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2023.104907 |
| URL الوصول: | https://doaj.org/article/150c72c68c42466f90f11b1e75850b6a |
| رقم الانضمام: | edsdoj.150c72c68c42466f90f11b1e75850b6a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2023.104907 |