MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary
                    Aldosteronism?

AbstractMicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.

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Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

Hormone and Metabolic Research ◽

10.1055/a-1120-8647 ◽

2020 ◽

Vol 52 (06) ◽

pp. 379-385

Author(s):

Lucie S. Meyer ◽

Siyuan Gong ◽

Martin Reincke ◽

Tracy Ann Williams

Keyword(s):

Angiotensin Ii ◽

Primary Aldosteronism ◽

Functional Role ◽

Adrenal Hyperplasia ◽

Endocrine Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Aldosterone Producing Adenoma ◽

Agonistic Autoantibodies

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

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Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology

Endocrinology ◽

10.1210/en.2017-00637 ◽

2017 ◽

Vol 158 (12) ◽

pp. 4129-4138 ◽

Cited By ~ 11

Author(s):

Leticia Aragao-Santiago ◽

Celso E Gomez-Sanchez ◽

Paolo Mulatero ◽

Ariadni Spyroglou ◽

Martin Reincke ◽

...

Keyword(s):

Mouse Models ◽

Primary Aldosteronism ◽

Genetic Basis ◽

Plasma Renin ◽

Adrenal Hyperplasia ◽

Endocrine Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Human Disorder ◽

Aldosterone Producing Adenoma ◽

Functional Mechanisms

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype–phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.

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The syndromes of low-renin hypertension: "separating the wheat from the chaff"

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302004000500013 ◽

2004 ◽

Vol 48 (5) ◽

pp. 674-681 ◽

Cited By ~ 9

Author(s):

Claudio E. Kater ◽

Edward G. Biglieri

Keyword(s):

Receptor Antagonist ◽

Myocardial Fibrosis ◽

Cardiac Remodeling ◽

Primary Aldosteronism ◽

Renin Activity ◽

Adrenal Hyperplasia ◽

Test Characteristics ◽

Low Renin Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Aldosterone Producing Adenoma

Primary aldosteronism (PA) is characterized by hypertension and suppressed renin activity with or without hypokalemia and comprises the aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia or idiopatic hyperaldosteronism (IHA). In recent series employing the aldosterone (aldo, ng/dL):renin (ng/mL·h) ratio (ARR) for screening, prevalence of PA among hypertensives soars to 8-20%; current predominance of IHA (>80%) over APA suggests the inclusion of former low-renin essential hypertensives (LREH), in whom plasma aldo can be reduced by suppressive maneuvers. We evaluated the test characteristics of the ARR obtained retrospectively from 127 patients with PA (81 APA; 46 IHA) and 55 with EH (30 LREH; 25 NREH) studied from 1975 to 1990. Using the combined ROC-defined cutoffs of 27 for the ARR and 12ng/dL for aldo, we obtained 89.8% sensitivity (Ss) and 98.2% specificity (Sp) in discriminating PA from EH: all APA and 72% of the IHA patients had values above these limits, but only one (3%) with LREH. Among the 46 IHA patients, 10 (21.7%) had ARR <27, four of whom with aldo <12ng/dL, virtually indistinguishable from LREH. Use of higher cutoff values (ARR >100; aldo >20) may attain 84%Ss and 82.6%Sp in separating APA from IHA. Because IHA and LREH ("the chaff") may be spectrum stages from the same disease, definite discrimination between these entities seems immaterial. However, precise identification of the APA ("the wheat") is critical, since it is the only surgically curable form of PA. Thus, while patients who may harbor an APA must be thoroughly investigated and surgically treated, non-tumoral disease (IHA and LREH) may be best treated with an aldo-receptor antagonist that will also prevent the aldo-mediated inflammatory effects involved in myocardial fibrosis and abnormal cardiac remodeling.

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Primary Aldosteronism: The Next Five Years

Hormone and Metabolic Research ◽

10.1055/s-0043-119802 ◽

2017 ◽

Vol 49 (12) ◽

pp. 977-983 ◽

Cited By ~ 11

Author(s):

John Funder

Keyword(s):

Primary Aldosteronism ◽

Germline Mutations ◽

Adrenal Hyperplasia ◽

Bilateral Disease ◽

The Past ◽

Wide Range ◽

Unilateral Disease ◽

Bilateral Adrenal Hyperplasia ◽

Aldosterone Producing Adenoma ◽

Current Guidelines

AbstractThe management of primary aldosteronism is widely varied within various published guidelines, with very little in the way of data supporting the choice of one variation over others. Current estimates of prevalence are probably accurate for aldosterone producing adenoma, but fall very short of that for bilateral adrenal hyperplasia. Discovery at the level of basic science has proven illuminating over the past 6 years in terms of unilateral disease and both somatic and germline mutations, with much less focus on the much more common bilateral disease; Attempts at harmonization have begun – for example, criteria for complete/partial/absent cure after adrenalectomy for unilateral disease; again focus on bilateral disease is muted. A number of possibilities are suggested as agenda for active consideration and change, across a wide range of areas – referral patterns, screening, confirmation and lateralization, what will be needed is discussion and agreement, to fill the lacunae within the current guidelines. Those involved will want to change to make such an agenda possible.

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Sensitive detection of melanoma metastasis using circulating microRNA expression profiles

Melanoma Research ◽

10.1097/cmr.0b013e328363e485 ◽

2013 ◽

Vol 23 (5) ◽

pp. 366-372 ◽

Cited By ~ 37

Author(s):

Rie Shiiyama ◽

Satoshi Fukushima ◽

Masatoshi Jinnin ◽

Junji Yamashita ◽

Azusa Miyashita ◽

...

Keyword(s):

Expression Profiles ◽

Microrna Expression ◽

Sensitive Detection ◽

Circulating Microrna ◽

Melanoma Metastasis

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Unilateral adrenalectomy in bilateral adrenal hyperplasia with primary aldosteronism

European Urology ◽

10.1016/s0302-2838(21)01061-7 ◽

2021 ◽

Vol 79 ◽

pp. S939-S940

Author(s):

Y-C. Lu ◽

K-H. Huang ◽

V-C. Wu ◽

K.D. Wu

Keyword(s):

Primary Aldosteronism ◽

Adrenal Hyperplasia ◽

Unilateral Adrenalectomy ◽

Bilateral Adrenal Hyperplasia

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Circulating microRNA expression profiles in pre-eclampsia: evidence of increased miR-885-5p levels

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/1471-0528.13903 ◽

2016 ◽

Vol 123 (13) ◽

pp. 2120-2128 ◽

Cited By ~ 28

Author(s):

VC Sandrim ◽

MR Luizon ◽

AC Palei ◽

JE Tanus-Santos ◽

RC Cavalli

Keyword(s):

Expression Profiles ◽

Microrna Expression ◽

Circulating Microrna

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Differences in MicroRNA Expression Profiles of Adrenocortical Tumors – Letter

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-10-0308 ◽

2010 ◽

Vol 16 (10) ◽

pp. 2915.1-2915 ◽

Cited By ~ 3

Author(s):

Zsófia Tömböl ◽

Peter M. Szabó ◽

Attila Patócs ◽

Károly Rácz ◽

Peter Igaz

Keyword(s):

Expression Profiles ◽

Microrna Expression ◽

Adrenocortical Tumors

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GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary aldosteronism

Acta Endocrinologica ◽

10.1530/eje-17-0946 ◽

2018 ◽

Vol 178 (3) ◽

pp. R101-R111 ◽

Cited By ~ 20

Author(s):

Silvia Monticone ◽

Fabrizio Buffolo ◽

Martina Tetti ◽

Franco Veglio ◽

Barbara Pasini ◽

...

Keyword(s):

Primary Aldosteronism ◽

Molecular Mechanisms ◽

Ion Homeostasis ◽

Germline Mutations ◽

Genetic Horizon ◽

Electrolyte Homeostasis ◽

Bilateral Adrenal Hyperplasia ◽

Aldosterone Producing Adenoma ◽

Mineralocorticoid Hormone ◽

Generation Sequencing

Aldosterone is the main mineralocorticoid hormone in humans and plays a key role in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction by the adrenal glands, affects 6% of the general hypertensive population and can be either sporadic or familial. Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) are the two most frequent subtypes of sporadic PA and 4 forms of familial hyperaldosteronism (FH-I to FH-IV) have been identified. Over the last six years, the introduction of next-generation sequencing has significantly improved our understanding of the molecular mechanisms responsible for autonomous aldosterone overproduction in both sporadic and familial PA. Somatic mutations in four genes (KCNJ5, ATP1A1, ATP2B3 and CACNA1D), differently implicated in intracellular ion homeostasis, have been identified in nearly 60% of the sporadic APAs. Germline mutations in KCNJ5 and CACNA1H cause FH-III and FH-IV, respectively, while germline mutations in CACNA1D cause the rare PASNA syndrome, featuring primary aldosteronism seizures and neurological abnormalities. Further studies are warranted to identify the molecular mechanisms underlying BAH and FH-II, the most common forms of sporadic and familial PA whose molecular basis is yet to be uncovered.

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