Circulating microRNAs as Diagnostic Markers in Primary Aldosteronism

SIMPLE SUMMARY: Many patients remain at increased risk of primary aldosteronism (PA) and its consequences due to the difficulty of accurate diagnosis. MicroRNAs circulating in the bloodstream are emerging as biomarkers for disease, particularly specific forms of cancer. In this review article, we argue that they may also have a role in the diagnosis of PA, if observed changes in the microRNA profile of PA tissue are reflected in circulating microRNAs, which can be sampled and analysed readily in a clinical setting. However, for various practical reasons, studies of potential diagnostic circulating microRNAs have often proved difficult to reproduce consistently. We describe these problems and how they might be overcome using, as an example, our design of the circulating microRNA arm of the ongoing ENS@T-HT project, which is intended to confirm whether circulating microRNAs can serve as biomarkers for PA. ABSTRACT: Primary aldosteronism (PA) is a common and highly treatable condition, usually resulting from adrenocortical tumorous growth or hyperplasia. PA is currently underdiagnosed owing to its complex and protracted diagnostic procedures. A simplified biomarker-based test would be highly valuable in reducing cardiovascular morbidity and mortality. Circulating microRNAs are emerging as potential biomarkers for a number of conditions due to their stability and accessibility. PA is known to alter microRNA expression in adrenocortical tissue; if these changes or their effects are mirrored in the circulating miRNA profile, then this could be exploited by a diagnostic test. However, the reproducibility of studies to identify biomarker-circulating microRNAs has proved difficult for other conditions due to a series of technical challenges. Therefore, any studies seeking to definitively identify circulating microRNA biomarkers of PA must address this in their design. To this end, we are currently conducting the circulating microRNA arm of the ongoing ENS@T-HT study. In this review article, we present evidence to support the utility of circulating microRNAs as PA biomarkers, describe the practical challenges to this approach and, using ENS@T-HT as an example, discuss how these might be overcome.