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
1 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 1088 Budapest, Szentkirályi str. 46., Hungary
2 MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, 1088 Budapest, Szentkirályi str. 46., Hungary
3 Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, 1088 Budapest, Szentkirályi str. 46., Hungary
4 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 USA
5 Endocrinology Unit, Department of Medicine, University of Padua, Via Ospedale, 105, 35128 Padova, Italy
6 Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia
7 Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
8 Medizinische Klinik und Poliklinik IV, Ludwig Maximilian University Munich, Munich, Germany
Introduction: Primary aldosteronism (PA), an important cause of secondary hypertension has two major subtypes: bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA). Treatment strategies of the two forms are largely different. Although it is invasive and requires great expertise, the best differentiating method of APA and BAH is adrenal venous sampling (AVS) at present. There is a major clinical need for a reliable and easily accessible diagnostic biomarker. Circulating microRNAs were shown to be useful as minimally invasive diagnostic markers in many diseases, so far, but their potential applicability in PA has not yet been investigated.
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. Next-generation sequencing (NGS) was performed on 30 EDTA-anticoagulated plasma samples. Significantly differently expressed miRNAs were validated by real-time RT-qPCR on all samples
Results: We have found relative overexpression of miR-30e-5p, miR-30d-5p, miR-223-3p and miR-7-5p in BAH compared to APA by NGS. Validation in 81 samples using qRT-PCR confirmed significant overexpression (p=0.03) of miR-7-5p. 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. Regarding the microRNA expressional variations, APA is more heterogenous at the miRNA level compared to BAH.
Conclusions: miR-7-5p was significantly overexpressed in BAH samples in comparison with APA samples, but its sensitivity and specificity values are not good enough for introduction to clinical practice, yet.
Doctoral School: Clinical Medicine (2)
Program: Hormonal Regulations (13)
Supervisor: Peter Igaz