Urine steroid metabolomics as a diagnostic tool in primary aldosteronism
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs.
Date Issued
2024-03-01
Date Acceptance
2023-12-13
Citation
The Journal of Steroid Biochemistry and Molecular Biology, 2024, 237
ISSN
0960-0760
Publisher
Elsevier
Journal / Book Title
The Journal of Steroid Biochemistry and Molecular Biology
Volume
237
Copyright Statement
© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38104729
PII: S0960-0760(23)00201-7
Subjects
Adenoma
Adrenal Cortex Neoplasms
Adrenocortical Adenoma
Adult
Aldosterone
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Humans
Hyperaldosteronism
Mass Spectrometry
Mutation
Steroids
Aldosterone-producing adenoma
Bilateral primary aldosteronism
Hybrid steroids
KCNJ5
Primary aldosteronism
Urine steroid metabolome
Publication Status
Published
Coverage Spatial
England
Article Number
106445
Date Publish Online
2023-12-15