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Primary aldosteronism.

ABSTRACT: Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identify patients who might benefit from effective and targeted treatment modalities. Effective treatments available include both surgical and medical approaches, usually dependent on the subtype of PA present. Our collective understanding of the pathophysiology of PA is expanded by recent developments in molecular biology and genetics, including understanding the specific somatic and germline mutations involved in pathogenesis. We review the pathophysiology, diagnostic workup, and treatment considerations for this disease process.

SUBMITTER: Wrenn SM

PROVIDER: S-EPMC7082264 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Primary aldosteronism.

Wrenn Sean M SM Vaidya Anand A Lubitz Carrie C CC

Gland surgery 20200201 1

Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identi ...[more]

PMID: 32206595

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Primary aldosteronism: a channelopathy?

Project description: Not available

| S-EPMC3977570 | biostudies-literature

Primary Aldosteronism and ARMC5 Variants.

Project description:ContextPrimary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia.ObjectiveWe investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects.MethodsPatients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods.ResultsWe identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023).ConclusionsGermline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension.

| S-EPMC4454793 | biostudies-literature

Characteristics and Outcomes in Primary Aldosteronism Patients Harboring Glucocorticoid-Remediable Aldosteronism.

Project description:The clinical characteristics and surgical prognosis of glucocorticoid-remediable aldosteronism (GRA, also known as familial hyperaldosteronism type 1, FH-I) have not been widely studied. Using data from the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry retrospectively, we describe the associated clinical factors for GRA and clinical predictors of surgical outcomes among identified GRA patients. We found 79 GRA-positive (51.2 ± 13.8 years; women 39 (49.4%)) and 114 GRA-negative primary aldosteronism (PA) patients matched with age, gender, and body mass index. Lower plasma aldosterone concentrations (PACs) and aldosterone-renin ratios were found among GRA-positive individuals. Multivariable logistic regression demonstrated that a PAC ≤ 40 ng/dL could predict concealed GRA individuals (OR 0.523, p = 0.037). Low serum potassium (OR 0.285, p = 0.008), but not the presence of GRA, was associated with hypertension-remission. Of note, PRA (OR 11.645, p = 0.045) and hypokalemia (OR 0.133, p = 0.048) were associated with hypertension-remission in GRA patients. Unilateral primary aldosteronism patients harboring concomitant GRA were not associated with inferior hypertension-remission after an adrenalectomy. Low serum potassium and high PRA were positively associated with hypertension-remission in GRA patients.

| S-EPMC8698750 | biostudies-literature

Risk of sepsis in patients with primary aldosteronism.

Project description:BACKGROUND:The interaction between hyperaldosteronism and immune dysfunction has been reported and glucocorticoid co-secretion is frequently found in primary aldosteronism (PA). The aforementioned conditions raise the possibility of the infection risk; however, clinical episodes of sepsis have not been reported in PA. METHODS:Using Taiwan's National Health Insurance Research Database between 1997 and 2009, we identified PA and aldosterone-producing adenoma (APA) matched with essential hypertension (EH) at a 1:1 ratio by propensity scores. The incidences of sepsis and mortality after the index date were evaluated, and the risk factors of outcomes were identified using adjusted Cox proportional hazards models and taking mortality as a competing risk. RESULTS:We enrolled 2448 patients with PA (male, 46.08%; mean age, 48.4 years). There were 875 patients who could be ascertained as APA. Taking mortality as the competing risk, APA patients had a lower incidence of sepsis than their matched EH patients (hazard ratio (HR) 0.29; P?<?0.001) after target treatments. Patients receiving adrenalectomy showed a benefit of decreasing the risk of sepsis (PA vs EH, HR 0.14, P?=?0.001; APA vs EH, HR 0.16, P?=?0.003), but mineralocorticoid receptor antagonist treatment may differ. Compared with matched control cohorts, patients with APA had a lower risk of all-cause mortality (PA, adjusted HR 0.84, P?=?0.050; APA, adjusted HR 0.31, P?<?0.001) after target treatments. CONCLUSIONS:Our study demonstrated that patients with PA/APA who underwent adrenalectomy could attenuate the risk of sepsis compared with their matched EH patients. We further found that APA patients with target treatments could decrease all-cause mortality compared with EH patients.

| S-EPMC6249889 | biostudies-other

Circulating miRNA Expression Profiling in Primary Aldosteronism.

Project description: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.

| S-EPMC6828819 | biostudies-literature

Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations.

Project description:Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding ?-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).

| S-EPMC4612399 | biostudies-literature

Primary aldosteronism: molecular medicine meets public health.

Project description:Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.

| S-EPMC7615304 | biostudies-literature

Circulating miRNA expression profiling in primary aldosteronism

Project description:Introduction: Primary aldosteronism (PA) is a major cause of secondary hypertension. The two principal forms of PA are bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) whose differentiation is clinically pivotal, due to their different treatments. Adrenal venous sampling (AVS) is considered to be the gold standard for the differentiation of the two clinical entities, but it is invasive, requires great expertise and is unavailable in many centers. There would be a major clinical need for a reliable and easily accessible diagnostic biomarker. Circulating microRNA were shown to be useful as minimally invasive diagnostic markers in many diseases, but their potential applicability in PA has not yet been investigated. 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. Next-generation sequencing (NGS) was performed on 30 EDTA-anticoagulated plasma samples. Significantly differently expressed miRNAs were validated by real-time RT-qPCR on all samples. Results: We have found relative overexpression of miR-30e-5p, miR-30d-5p, miR-223-3p and miR-7-5p in BAH compared to APA by NGS. Validation of 81 samples confirmed significant overexpression (p=0.03) of miR-7-5p. Regarding the microRNA expressional variations, APA is more heterogenous at the miRNA level compared to BAH. Conclusion: 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 yet.

2019-02-12 | GSE126386 | GEO

Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth.

Project description:Aldosterone-producing adenomas with somatic mutations in the KCNJ5 G-protein-coupled inwardly rectifying potassium channel are a cause of primary aldosteronism. These mutations drive aldosterone excess, but their role in cell growth is undefined. Our objective was to determine the role of KCNJ5 mutations in adrenal cell proliferation and apoptosis. The Ki67 proliferative index was positively correlated with adenoma diameter in aldosterone-producing adenomas with a KCNJ5 mutation (r=0.435, P=0.007), a negative correlation was noted in adenomas with no mutation detected (r=-0.548, P=0.023). Human adrenocortical cell lines were established with stable expression of cumate-inducible wild-type or mutated KCNJ5. Increased cell proliferation was induced by low-level induction of KCNJ5-T158A expression compared with control cells (P=0.009), but increased induction ablated this difference. KCNJ5-G151R displayed no apparent proliferative effect, but KCNJ5-G151E and L168R mutations each resulted in decreased cell proliferation (difference P<0.0001 from control cells, both comparisons). Under conditions tested, T158A had no effect on apoptosis, but apoptosis increased with expression of G151R (P<0.0001), G151E (P=0.008), and L168R (P<0.0001). We generated a specific KCNJ5 monoclonal antibody which was used in immunohistochemistry to demonstrate strong KCNJ5 expression in adenomas without a KCNJ5 mutation and in the zona glomerulosa adjacent to adenomas irrespective of genotype as well as in aldosterone-producing cell clusters. Double immunofluorescence staining for KCNJ5 and CYP11B2 (aldosterone synthase) showed markedly decreased KCNJ5 immunostaining in CYP11B2-positive cells compared with CYP11B2-negative cells in aldosterone-producing adenomas with a KCNJ5 mutation. Together, these findings support the concept that cell growth effects of KCNJ5 mutations are determined by the expression level of the mutated channel.

| S-EPMC6739168 | biostudies-literature

Obesity and the diagnostic accuracy for primary aldosteronism.

Project description:The effects of body mass index on the diagnostic accuracy of primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. The current study included 59 adult patients who underwent a stepwise evaluation for PA, using aldosterone to renin ratio for case detection and plasma aldosterone concentration after saline suppression test and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Body mass index had a quadratic (U-shaped) correlation with plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, and plasma aldosterone concentration after saline suppression test. Among patients with a body mass index ≥30 kg/m2 , the aldosterone to renin ratio yielded lower case detection accuracy of PA. We conclude that obesity results in a nonlinear correlation with plasma aldosterone concentration, plasma renin activity, and aldosterone to renin ratio, which affects the accuracy of case detection for PA. Patients with a body mass index ≥30 kg/m2 are less accurately identified as having PA when saline suppression and/or oral salt loading tests are used for case confirmation.

| S-EPMC5602533 | biostudies-literature

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