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.
18 - 21 May 2019
European Society of Endocrinology