{Reference Type}: Journal Article
{Title}: Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.
{Author}: Braun LT;Osswald A;Zopp S;Rubinstein G;Vogel F;Riester A;Honegger J;Eisenhofer G;Constantinescu G;Deutschbein T;Quinkler M;Elbelt U;Künzel H;Nowotny HF;Reisch N;Hartmann MF;Beuschlein F;Pons-Kühnemann J;Reincke M;Wudy SA;
{Journal}: EBioMedicine
{Volume}: 99
{Issue}: 0
{Year}: 2024 Jan 20
{Factor}: 11.205
{DOI}: 10.1016/j.ebiom.2023.104907
{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).
RESULTS: 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%.
CONCLUSIONS: GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes.
BACKGROUND: The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung.