ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP198 | DOI: 10.1530/endoabs.63.GP198

Analysis of circulating microRNAs in primary aldosteronism

Abel Decmann1, Gábor Nyírő2, Ottó Darvasi3, Péter Turai1, Irina Bancos4, Raffaele Pezzani5, Ivana Kraljevic6, Darko Kastelan6, Mirko Parasiliti-Caprino7, Nina Nirschl8, Daniel Heinrich8, Attila Patócs3 & Peter Igaz1,2


12nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; 2MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; 3Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; 4Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, USA; 5Endocrinology Unit, Department of Medicine, University of Padua, Padova, Italy; 6Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia; 7Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy; 8Medizinische Klinik und Poliklinik IV, Ludwig Maximilian University Munich, Munich, Germany.


Introduction: Primary aldosteronism (PA) is a major cause of secondary hypertension. The two major forms of sporadic PA (aldosterone producing adenoma – APA and bilateral adrenal hyperplasia – BAH) can only be reliably differentiated by adrenal venous sampling (AVS). Several mutations have been described for APA, but the pathogenesis of BAH is poorly elucidated. Differentiation of APA and BAH is clinically pivotal, as their treatment is different. There is no blood-borne marker for the differentiation of APA and BAH.

Aims: To determine and compare the circulating microRNA expression profiles of AVS-confirmed APA and BAH plasma samples, and to evaluate their applicability as minimally invasive markers.

Methods: 81 AVS-confirmed plasma samples were included (43 APA and 38 BAH). Next-generation sequencing (NGS) on 30 EDTA-anticoagulated plasma samples (16 APA and 14 BAH) was performed by Illumina MiSDefault (discovery cohort). Significantly differentially expressed microRNAs were validated by real-time RT-qPCR. The validation cohort included 30 samples of the discovery cohort (technical validation) and further 27 APAs and 24 BAHs.

Results: We have found relative overexpression of miR-30e-5p, miR-223-3p, miR-30d-5p and miR-7-5p in BAH compared to APA by NGS. Validation of 81 samples showed significant overexpression (P=0.03) of miR-7-5p in BAH samples compared to APA samples. A negative predictive value of 86.7% could be achieved to exclude BAH by a miR-7-5p dCT cut-off value of −18.9. No correlation between dCT values and hormonal parameters was found. APA samples displayed considerable heterogeneity in circulating microRNA expression, whereas BAH were much more homogeneous.

Conclusion: APA is more heterogeneous at the microRNA level compared to BAH. miR-7-5p was significantly overexpressed in BAH samples compared to APA samples, but its sensitivity and specificity values are not good enough for introduction to the clinical practice at present.