Genetics of primary hyperaldosteronism

Dutta, Ravi Kumar; Söderkvist, Peter; Gimm, Oliver

doi:10.1530/erc-16-0055

Cited by 31 publications

(22 citation statements)

References 95 publications

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“…This triggers the production of aldosterone. This figure is modified from previously published figure (Dutta et al 2016) Angiotensin II binds to angiotensin II type 1 (AT1) receptors on the surface of ZG cells which activates the secondary messenger inositol 1,4,5-triphosphate (IP3) and diacylglycerol ( Figure 2) 12,13 . IP3 trigger the export of Ca 2+ from the endoplasmic reticulum through IP3 receptors, increasing cytosolic Ca 2+ that activates the Ca 2+ /calmodulin-dependent protein kinases (CaMKs).…”

Section: Aldosterone and Blood Pressurementioning

confidence: 99%

Genetic and molecular alterations in aldosterone producing adenomas

Dutta

2020

Linköping University Medical Dissertations

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Aldosterone producing tumors (APA, also known as Conn tumors) are adrenal tumors that overproduce aldosterone, a hormone that regulates the sodium levels in blood and contributes to blood pressure (BP) regulation. Excessive production of aldosterone causes hypertension and approximately 5-15% of hypertensive patients have hyperaldosteronism, known as primary aldosteronism (PA). Major causes of PA are bilateral adrenal hyperplasia (BAH) or aldosterone producing adenoma (APA) and about 30% of PA patients have APAs. In most cases, the disease is unilateral, in rare case bilateral. Patients with APA are often detected when they have elevated blood pressure (BP>160/100mmHg) or when BP cannot be controlled with drugs. Surgery dramatically normalizes or lowers BP in patients with APA.

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Section: Aldosterone and Blood Pressurementioning

confidence: 99%

Genetic and molecular alterations in aldosterone producing adenomas

Dutta

2020

Linköping University Medical Dissertations

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“…The channel contains four repeat domains (I-IV), each composed of six transmembrane segments (S1-S6), plus a membraneassociated loop between S5 and S6 (Catterall 2010). The S4 segment is involved in voltage sensing for activation, whereas S5, S6 and the loop between these two segments form the pore lining of the channel (Dutta et al 2016). Cav1.3 is one of the most abundant calcium channels in normal human adrenal and in APA, predominantly expressed in ZG (Scholl et al 2013, Daniil et al 2016.…”

Section: R51 Review F L Fernandes-rosa S Boulkroun and Othersmentioning

confidence: 99%

Somatic and inherited mutations in primary aldosteronism

Fernandes-Rosa

Boulkroun

Zennaro

2017

Journal of Molecular Endocrinology

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Primary aldosteronism (PA), the most common form of secondary hypertension, is caused in the majority of cases by unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Over the past few years, somatic mutations in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have been proven to be associated with APA development, representing more than 50% of sporadic APA. The identification of these mutations has allowed the development of a model for APA involving modification on the intracellular ionic equilibrium and regulation of cell membrane potential, leading to autonomous aldosterone overproduction. Furthermore, somatic CTNNB1 mutations have also been identified in APA, but the link between these mutations and APA development remains unknown. The sequence of events responsible for APA formation is not completely understood, in particular, whether a single hit or a double hit is responsible for both aldosterone overproduction and cell proliferation. Germline mutations identified in patients with early-onset PA have expanded the classification of familial forms (FH) of PA. The description of germline KCNJ5 and CACNA1H mutations has identified FH-III and FH-IV based on genetic findings; germline CACNA1D mutations have been identified in patients with very early-onset PA and severe neurological abnormalities. This review summarizes current knowledge on the genetic basis of PA, the association of driver gene mutations and clinical findings and in the contribution to patient care, plus the current understanding on the mechanisms of APA development.

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“…However, »very severe« mutations may become lethal for the affected adrenocortical cell thus preventing formation of hyperplastic or adenomatous tissue [75]. In addition, there are more genes to be associated with aldosterone production [76], and other »non-channelopathy« mutations are also known to be associated with aldosteronomas, including aberrations in the wnt-β-catenin pathway [67,[77][78][79][80][81][82]. Of note, aldosteronomas are inhomogeneous tumors with variable degrees of CYP11B2 expression and underlying genetic changes [83].…”

Section: Co-secretion Of Glucocorticoidsmentioning

confidence: 99%

How to Escape from Primary Aldosteronism? News and Views on an Adrenal Disorder of Salt Retention

Willenberg

2017

Horm Metab Res

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The last years have seen substantial progress in primary aldosteronism (PA), which is the most common cause of secondary hypertension. Many programs have been established around the world to meet the needs in healthcare and the management of patients with PA according to published guidelines and clinical protocols. Systematic analysis of emerging data and meticulous scientific work have informed us on the molecular basis of the disease and helped to characterize hereditary forms of PA. Techniques have been developed to better diagnose PA and to establish genotype-phenotype relationships and their impact on hypertension. Studies have been undertaken to stratify patients for risk factors and to ensure quality of best medical treatment. This review focuses on some clinically relevant problems in characterizing autonomous aldosterone secretion and discusses testing and management strategies. Besides, this review puts the emphasis on some colorful studies not to pale soon beside an ever evolving painting background.

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Genetics of primary hyperaldosteronism

Cited by 31 publications

References 95 publications

Genetic and molecular alterations in aldosterone producing adenomas

Genetic and molecular alterations in aldosterone producing adenomas

Somatic and inherited mutations in primary aldosteronism

How to Escape from Primary Aldosteronism? News and Views on an Adrenal Disorder of Salt Retention

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