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Cardiovascular Endocrinology

SUN-246 - Validation of A Circulating microRNA Combination for Lateralizing Primary Aldosteronism: A Multi-Center Machine Learning Study

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Peter Igaz, MD MSc PhD DSc: No financial relationships to disclose


Background: We previously identified 6 circulating microRNAs (miRNAs) (miR-146a-5p, miR-24-3p, miR-130b-3p, miR-99b-5p, miR-151a-3p, miR-199a-3p) that in combination could distinguish unilateral primary aldosteronism (UPA) from bilateral adrenal hyperplasia (BAH) using neural network and deep learning approaches. Validation remains the critical bottleneck for clinical translation of PA prediction models.

Aim: To validate the clinical utility of the miRNA combination in a larger cohort of PA patients.

Methods: 205 peripheral plasma samples from patients with confirmed PA under an international collaboration of 9 expert centers were included (101 UPA and 104 BAH). All patients underwent adrenal venous sampling. Plasma miRNA expression was quantified by RT-qPCR. We expanded our analytical framework to six machine learning algorithms: the original neural network and deep learning models, plus Random Forest, XGBoost, Support Vector Machine, Logistic Regression and Naive Bayes.

Results: Initial cross-center and cross-time heterogeneity prompted a plate-wise Z-score based solution, which successfully enabled model generalization across centers and cohorts. Critically, validation performance matched the training performance. On a 313 strong harmonized dataset combining our original 108 (published in 2024) and this additional 205 patient validation cohorts (altogether 155 UPA and 158 BAH), the combined performance of the models yielded an area under curve (AUC) of 81.5% and regarding BAH a specificity of 84.3%, a positive predictive value of 80% and an overall F1 score of 72.5%.

Conclusion: This study presents a harmonization framework for cross-center application of circulating microRNA-based lateralization of PA. The combined ensemble performance across 313 samples of 81.5% AUC represents a robust, clinically generalizable performance from this method, however further cohort expansion may increase clinical utility, thus expediting care for PA patients worldwide by the simplification of patient pathways, as PA cases confirmed as bilateral can avoid further cumbersome and expensive lateralization procedures.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*