The average age for its diagnosis was 51 years, and no gender difference was observed. The average size of tumors was 10.2 cm. Congenital adrenal hyperplasia was associated to 10% of all cases analyzed, while other adrenal hypersecretory disorders (cortisol, aldosterone) were found in 7.5% of cases. Computed tomography and magnetic resonance imaging can be reliably used for its differential diagnosis. If the diagnosis of an adrenal myelolipoma is unambiguous, and no associated symptoms or hormonal activity are established, surgical intervention is usually not necessary.

There is no available blood marker for the preoperative diagnosis of adrenocortical malignancy. The objective of this study was to investigate the expression of extracellular vesicle-associated microRNAs and their diagnostic potential in plasma samples of patients suffering from adrenocortical tumors. Extracellular vesicles were isolated either by using Total Exosome Isolation Kit or by differential centrifugation/ultracentrifugation. Preoperative plasma extracellular vesicle samples of 6 adrenocortical adenomas (ACA) and 6 histologically verified adrenocortical cancer (ACC) were first screened by Taqman Human Microarray A-cards. Based on the results of screening, two miRNAs were selected and validated by targeted quantitative real-time PCR. The validation cohort included 18 ACAs and 16 ACCs. Beside RNA analysis, extracellular vesicle preparations were also assessed by transmission electron microscopy, flow cytometry and dynamic light scattering. Significant overexpression of hsa-miR-101 and hsa-miR-483-5p in ACC relative to ACA samples has been validated. Receiver operator characteristics of data revealed dCThsa-miR-483-5p normalized to cel-miR-39 to have the highest diagnostic accuracy (area under curve 0.965), the sensitivity and the specifity were 87.5 and 94.44, respectively. Extracellular vesicle-associated hsa-miR-483-5p thus appears to be a promising minimally invasive biomarker in the preoperative diagnosis of ACC but needs further validation in larger cohorts of patients.

MicroRNAs are short non-protein coding RNA molecules involved in the epigenetic regulation of gene expression. Recently, extracellular microRNAs have been described in body fluids that might enable epigenetic communication between distant tissues. Being highly conserved molecules, exogenous xenomicroRNAs from different species could affect gene expression in the host even in a cross-kingdom fashion. Several data underline the relevance of microRNA-mediated communication between virus and host, and there are some experimental data showing that plant-or animal-derived dietary microRNAs might have gene expression modulating activity in humans. Milk-derived microRNAs might be involved in the "epigenetic priming" of the baby. Exogenous microRNAs might be hypothesized to be implicated in disease pathogenesis, e.g. in tumors. Major questions remain to be addressed including the amount of xeno-microRNAs needed for biological action or routes for microRNA delivery. In this brief review, experimental data and hypotheses on the potential pathogenic inter-species relevance of microRNA are presented.Abbreviations: AGO2, Argonaute-2 protein; dsRNA, double stranded RNA; FoxO1, forkhead box class O1A; FOXP3, forkhead box P3; HDL, high density lipoprotein; LDL, low density lipoprotein; LDLRAP1, low-density lipoprotein receptor adapter protein 1; miRNA, miR, microRNA; mTORC1, mechanistic target of rapamycin complex 1; premiRNA, precursor microRNA; pri-miRNA, primary microRNA; RISC, RNA-induced silencing complex; RUNX2, runt related transcription factor 2; siRNA, small interfering RNA; TCF7, transcription factor 7; TLR, Toll-like receptor; Treg, regulatory T-cell; ZEB1, zinc finger E-box binding homeobox 1

We have found significantly differentially expressed miRNAs in AML and adrenocortical tumors. Circulating hsa-miR-451a might be a promising minimally invasive biomarker of AML. The lack of significantly different expression of hsa-miR-483-3p and hsa-miR-483-5p between AML and ACC might limit their applicability as diagnostic miRNA markers for ACC.

No abstract

Objective: Primary aldosteronism is a major cause of secondary hypertension. Its two principal forms are bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) whose differentiation is clinically pivotal. There is a major clinical need for a reliable and easily accessible diagnostic biomarker for case identification and subtyping. Circulating microRNAs were shown to be useful as minimally invasive diagnostic markers. Our aim was to determine and compare the circulating microRNA expression profiles of adenoma and hyperplasia plasma samples, and to evaluate their applicability as minimally invasive markers. Methods: One hundred and twenty-three samples from primary aldosteronism patients were included. Next-generation sequencing was performed on 30 EDTA-anticoagulated plasma samples (discovery cohort). Significantly differently expressed miRNAs were validated by real-time reverse transcription-qPCR in an independent validation cohort (93 samples). Results: We have found relative overexpression of miR-30e-5p, miR-30d-5p, miR-223-3p, and miR-7-5p in hyperplasia compared to adenoma by next-generation sequencing. Validation by qRT-PCR confirmed significant overexpression of hsa-miR-30e-5p, hsa-miR-30d-5p, and hsa-miR-7-5p in hyperplasia samples. Regarding the microRNA expressional variations, adenoma is more heterogeneous at the miRNA level compared to hyperplasia. Conclusion: Three microRNAs were significantly overexpressed in hyperplasia samples compared to adenoma samples, but their sensitivity and specificity values are not good enough for introduction to clinical practice.

EV-associated miRNAs are differentially expressed in different non-functioning and cortisol-producing adrenocortical tumors.

Non-coding RNA molecules including microRNAs and long non-coding RNAs (lncRNA) have been implicated in the pathogenesis of several tumors and numerous data support their applicability in diagnosis as well. Despite recent advances, the pathogenesis of adrenocortical cancer still remains elusive and there are no reliable blood-borne markers of adrenocortical malignancy, either. Several findings show the potential applicability of microRNAs as biomarkers of malignancy and prognosis, and there are some data on lncRNA as well. In this review, we present a synopsis on the potential relevance of non-coding RNA molecules in adrenocortical pathogenesis and their applicability in diagnosis from tissue and blood.