Dataset Information

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.

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)/(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.

SUBMITTER: Braun LT

PROVIDER: S-EPMC10776922 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.

Braun Leah T LT Osswald Andrea A Zopp Stephanie S Rubinstein German G Vogel Frederick F Riester Anna A Honegger Jürgen J Eisenhofer Graeme G Constantinescu Georgiana G Deutschbein Timo T Quinkler Marcus M Elbelt Ulf U Künzel Heike H Nowotny Hanna F HF Reisch Nicole N Hartmann Michaela F MF Beuschlein Felix F Pons-Kühnemann Jörn J Reincke Martin M Wudy Stefan A SA

EBioMedicine 20231220

<h4>Background</h4>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.<h4>Methods</h4>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 diseas ...[more]

PMID: 38128413

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Dataset Information

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.

Background

Methods

Findings

Interpretation

Funding

Publications

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.

Similar Datasets

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