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Fulltext Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations

Teo AE, Garg S, Shaikh LH, Zhou J, Karet Frankl FE, Gurnell M, et al.

N Engl J Med, 2015 Oct 08;373(15):1429-36.
PMID: 26397949 DOI: 10.1056/NEJMoa1504869

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 β-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.).

Matched MeSH terms: Aldosterone/secretion
Fulltext The blood pressure variability, arterial elasticity and humoral factors in subjects with family history of hypertension

Rafidah HM, Azizi A, Suhaimi H, Noriah MN

Med J Malaysia, 2008 Mar;63(1):9-16.
PMID: 18935724 MyJurnal

Normotensive subjects with family history of hypertension (FHT) have been reported to have increased left ventricular mass index and reduced ventricular compliance. Of interest is whether blood pressure variability (BPV), which has been associated with target organ damage, is then part of this complex inherited syndrome? The objectives of this study are to determine whether there are any significant differences in BPV, arterial compliance and humoral factors in subjects with FHT as compared to controls. Thirty-five subjects with self reported FHT and 35 matched controls underwent 24 hour BP monitoring (BR-102, Schiller Inc. Germany). Arterial compliance was measured using systolic pulse wave tonometry (HDI/Pulsewave Cardiovascular Profiling Instrument, Hypertension Diagnostic Inc. USA). None of the subjects were hypertensive or diabetic. Out of these numbers, 25 subjects with FHT and 26 controls had measurements of plasma catecholamines, plasma renin and serum aldosterone. Catecholamines were assayed with high performance liquid chromatography, while both renin and aldosterone measurements were by radioimmunoassay. Subjects with FHT have higher night time BPV. There was no significant difference in arterial compliances between both groups. There were increased level of norepinephrine (NE) in subjects with FHT but epinephrine (E), renin and aldosterone levels were similar in both groups. There were no correlations between NE and BPV but E was negatively associated with daytime and mean arterial systolic BPV. In conclusion subjects with FHT demonstrated a higher night time BPV and NE level as compared to controls.

Matched MeSH terms: Aldosterone/blood*
Histone demethylase LSD1 and biological sex: impact on blood pressure and aldosterone production

Huang Y, Ting PY, Yao TM, Homma T, Brooks D, Katayama Rangel IA, et al.

J Endocrinol, 2018 Nov 01.
PMID: 30400034 DOI: 10.1530/JOE-18-0247

Human risk allele carriers of Lysine-Specific Demethylase 1 (LSD1) and LSD1 deficient mice have salt sensitive hypertension for unclear reasons. We hypothesized that LSD1 deficiency causes dysregulation of aldosterone's response to salt intake resulting in increased cardiovascular risk factors [blood pressure and microalbumin]. Furthermore, we determined the effect of biological sex on these potential abnormalities. To test our hypotheses, LSD1 male and female heterozygote knockout (LSD1+/-) and wild type (WT) mice were assigned to two age groups: 18 weeks and 36 weeks. Plasma aldosterone levels and aldosterone production from zona glomerulosa cells studied ex vivo were greater in both male and female LSD1+/- mice consuming a liberal salt diet as compared to WT mice consuming the same diet. However, salt sensitive blood pressure elevation and increased microalbuminuria were only observed in male LSD1+/- mice. These data suggest that LSD1 interacts with aldosterone's secretory response to salt intake. Lack of LSD1 causes inappropriate aldosterone production on a liberal salt diet; males appear to be more sensitive to this aldosterone increase as males, but not females, develop salt sensitivity of blood pressure and increased microalbuminuria. The mechanism responsible for the cardiovascular protective effect in females is uncertain but may be related to estrogen modulating the effect of mineralocorticoid receptor activation.

Matched MeSH terms: Aldosterone
Biological sex modifies aldosterone's secretion at a cellular level

Gholami SK, Tay CS, Lee JM, Zagoren E, Maris SA, Wong JY, et al.

J Endocrinol, 2021 11 24;252(1):1-13.
PMID: 34643545 DOI: 10.1530/JOE-21-0126

Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues' levels. This study's goal was to determine whether ALDO's biosynthesis also differed by sex. Two approaches were used. First, plasma renin activity and aldosterone were measured in rats. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex vivo areas: (1) activity/levels of early steps in ALDO's biosynthesis (StAR and CYP11A1); (2) activity/levels of a late step (CYP11B2); and (3) the status of the mineralocorticoid receptor (MR)-mediated, ultrashort feedback loop. Females had higher expression of CYP11A1 and StAR and increased CYP11A1 activity (increased pregnenolone/corticosterone levels) but did not differ in CYP11B2 expression or activity (ALDO levels). Activating the ZG's MR (thereby activating the ultrashort feedback loop) reduced CYP11B2's activity similarly in both sexes. Exvivo, these molecular effects were accompanied, in females, by lower ALDO basally but higher ALDO with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of ALDO's biosynthesis but also these differences at the molecular level help explain the variable reports on ALDO's circulating levels. Basally, both in vivo and ex vivo, males had higher ALDO levels, likely secondary to higher ALDO secretagogue levels. However, in response to acute stimulation, ALDO levels are higher in females because of the greater levels and/or activity of their StAR/CYP11A1.

Matched MeSH terms: Aldosterone/metabolism*
Fulltext Lysine-specific demethylase 1 deficiency modifies aldosterone synthesis in a sex-specific manner

Tan YJD, Brooks DL, Wong KYH, Huang Y, Romero JR, Williams JS, et al.

J Endocrinol, 2023 Jan 01;256(1).
PMID: 36327153 DOI: 10.1530/JOE-22-0141

Biologic sex influences the development of cardiovascular disease and modifies aldosterone (ALDO) and blood pressure (BP) phenotypes: females secrete more ALDO, and their adrenal glomerulosa cell is more sensitive to stimulation. Lysine-specific demethylase 1 (LSD1) variants in Africans and LSD1 deficiency in mice are associated with BP and/or ALDO phenotypes. This study, in 18- and 40-week-old wild type (WT) and LSD1+/- mice, was designed to determine whether (1) sex modifies ALDO biosynthetic enzymes; (2) LSD1 deficiency disrupts the effect of sex on these enzymes; (3) within each genotype, there is a positive relationship between ALDO biosynthesis (proximate phenotype), plasma ALDO (intermediate phenotype) and BP levels (distant phenotype); and (4) sex and LSD1 genotype interact on these phenotypes. In WT mice, female sex increases the expression of early enzymes in ALDO biosynthesis but not ALDO levels or systolic blood pressure (SBP). However, enzyme expressions are shifted downward in LSD1+/- females vs males, so that early enzyme levels are similar but the late enzymes are substantially lower. In both age groups, LSD1 deficiency modifies the adrenal enzyme expressions, circulating ALDO levels, and SBP in a sex-specific manner. Finally, significant sex/LSD1 genotype interactions modulate the three phenotypes in mice. In conclusion, biologic sex in mice interacts with LSD1 deficiency to modify several phenotypes: (1) proximal (ALDO biosynthetic enzymes); (2) intermediate (circulating ALDO); and (3) distant (SBP). These results provide entry to better understand the roles of biological sex and LSD1 in (1) hypertension heterogeneity and (2) providing more personalized treatment.

Matched MeSH terms: Aldosterone/metabolism
Fulltext Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore

Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young WF

J Clin Endocrinol Metab, 2000 Aug;85(8):2854-9.
PMID: 10946893

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

Matched MeSH terms: Aldosterone/blood
Fulltext LGR5 Activates Noncanonical Wnt Signaling and Inhibits Aldosterone Production in the Human Adrenal

Shaikh LH, Zhou J, Teo AE, Garg S, Neogi SG, Figg N, et al.

J Clin Endocrinol Metab, 2015 Jun;100(6):E836-44.
PMID: 25915569 DOI: 10.1210/jc.2015-1734

CONTEXT: Aldosterone synthesis and cellularity in the human adrenal zona glomerulosa (ZG) is sparse and patchy, presumably due to salt excess. The frequency of somatic mutations causing aldosterone-producing adenomas (APAs) may be a consequence of protection from cell loss by constitutive aldosterone production.
OBJECTIVE: The objective of the study was to delineate a process in human ZG, which may regulate both aldosterone production and cell turnover.
DESIGN: This study included a comparison of 20 pairs of ZG and zona fasciculata transcriptomes from adrenals adjacent to an APA (n = 13) or a pheochromocytoma (n = 7).
INTERVENTIONS: Interventions included an overexpression of the top ZG gene (LGR5) or stimulation by its ligand (R-spondin-3).
MAIN OUTCOME MEASURES: A transcriptome profile of ZG and zona fasciculata and aldosterone production, cell kinetic measurements, and Wnt signaling activity of LGR5 transfected or R-spondin-3-stimulated cells were measured.
RESULTS: LGR5 was the top gene up-regulated in ZG (25-fold). The gene for its cognate ligand R-spondin-3, RSPO3, was 5-fold up-regulated. In total, 18 genes associated with the Wnt pathway were greater than 2-fold up-regulated. ZG selectivity of LGR5, and its absence in most APAs, were confirmed by quantitative PCR and immunohistochemistry. Both R-spondin-3 stimulation and LGR5 transfection of human adrenal cells suppressed aldosterone production. There was reduced proliferation and increased apoptosis of transfected cells, and the noncanonical activator protein-1/Jun pathway was stimulated more than the canonical Wnt pathway (3-fold vs 1.3-fold). ZG of adrenal sections stained positive for apoptosis markers.
CONCLUSION: LGR5 is the most selectively expressed gene in human ZG and reduces aldosterone production and cell number. Such conditions may favor cells whose somatic mutation reverses aldosterone inhibition and cell loss.

Matched MeSH terms: Aldosterone/biosynthesis*
Protein kinase D2 regulates epithelial sodium channel activity and aldosterone non-genomic responses in renal cortical collecting duct cells

Thomas W, Dooley R, Quinn S, Robles MY, Harvey BJ

Steroids, 2020 03;155:108553.
PMID: 31836481 DOI: 10.1016/j.steroids.2019.108553

Protein kinase D2 (PKD2) is a serine/threonine protein kinase which plays an important role in vesicle fission at the trans-Golgi network (TGN) to coordinate subcellular trafficking with gene expression. We found that in the rat kidney, PKD2 is specifically expressed in collecting duct principal cells predominantly at the apical membrane and with lower basal expression in cytosolic compartments. When rats were maintained on a Na+ depleted diet (<0.87 mmol Na+/kg) to increase plasma aldosterone levels, PKD2 became internalized to a cytoplasmic compartment. Treatment of murine M1 cortical collecting duct (M1-CCD) cells with aldosterone (10 nM) promoted PKD2 co-localization with the trans-Golgi network within 30 min. PKD2 underwent autophosphorylation at Ser876 within 10 min of aldosterone treatment and remained phosphorylated (active) for at least 24 h. A stable PKD2 shRNA knock-down (PKD2 KD) M1-CCD cell line was developed to study the role of PKD2 in epithelial Na+ channel (ENaC) trafficking and transepithelial Na+ transport (SCC) in epithelial monolayers grown in Ussing chambers. The PKD2 KD cells developed transepithelial resistance with kinetics equivalent to wild-type cells, however the transepithelial voltage and Na+ current were significantly elevated in PKD2 knock-down CCD epithelia. The higher basal SCC was due to increased ENaC activity. Aldosterone treatment for 24 h resulted in a decline in ENaC activity in the PKD2 KD cells as opposed to the increase observed in the wild-type cells. The paradoxical inhibition of SCC by aldosterone in PKD2 KD epithelium was attributed to a reduction in ENaC current and lower membrane abundance of ENaC, demonstrating that PKD2 plays a critical tonic role in ENaC trafficking and channel subunit stability. The rapid activation of PKD2 by aldosterone is synergistic with the transcriptional activity of MR and contributes to increased ENaC activity.

Matched MeSH terms: Aldosterone/blood; Aldosterone/pharmacology*
Aldosterone-induced protein kinase signalling and the control of electrolyte balance

Harvey BJ, Thomas W

Steroids, 2018 05;133:67-74.
PMID: 29079406 DOI: 10.1016/j.steroids.2017.10.009

Aldosterone acts through the mineralocorticoid receptor (MR) to modulate gene expression in target tissues. In the kidney, the principal action of aldosterone is to promote sodium conservation in the distal nephron and so indirectly enhance water conservation under conditions of hypotension. Over the last twenty years the rapid activation of protein kinase signalling cascades by aldosterone has been described in various tissues. This review describes the integration of rapid protein kinase D signalling responses with the non-genomic actions of aldosterone and transcriptional effects of MR activation.

Matched MeSH terms: Aldosterone/metabolism*
Changes in plasma aldosterone and electrolytes levels, kidney epithelial sodium channel (ENaC) and blood pressure in normotensive WKY and hypertensive SHR rats following gonadectomy and chronic testosterone treatment

Loh SY, Giribabu N, Salleh N

Steroids, 2017 Dec;128:128-135.
PMID: 28954214 DOI: 10.1016/j.steroids.2017.09.008

We hypothesized that testosterone-induced increase in blood pressure involve changes in aldosterone levels and expression of epithelial sodium channel (ENaC) in the kidneys.
METHODS: Ovariectomized female normotensive Wistar Kyoto (WKY) and Spontaneous hypertensive (SHR) rats were given six weeks treatment with testosterone via subcutaneous silastic implant. The rats were anesthetized and mean arterial pressure (MAP) was measured via direct cannulation of the carotid artery. Animals were sacrificed and kidneys were removed and subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time polymerase chain reaction (qPCR), respectively. Distributions of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Plasma testosterone, aldosterone, electrolytes, osmolality, urea and creatinine levels were determined by biochemical assays. Analysis were also performed in non-testosterone treated orchidectomized and sham-operated male WKY and SHR rats.
RESULTS: Treatment of ovariectomized female WKY and SHR rats with testosterone causes increased in MAP but decreased in plasma aldosterone, sodium (Na+), osmolality and expression and distribution of α, β and γ-ENaC subunits in the kidneys. Orchidectomy decreased the MAP but increased plasma aldosterone, Na+, osmolality and α, β and γ-ENaC expression and distribution in the kidneys of male WKY and SHR rats.
CONCLUSIONS: Decreased in plasma aldosterone, Na+ and ENaC levels in kidneys under testosterone influence indicated that testosterone-induced increased in MAP were not due to increased plasma aldosterone and ENaC levels in kidneys, and thus the testosterone effect on MAP likely involve other mechanisms.

Matched MeSH terms: Aldosterone/administration & dosage*; Aldosterone/blood
Fulltext Regulation of aldosterone secretion by Cav1.3

Xie CB, Shaikh LH, Garg S, Tanriver G, Teo AE, Zhou J, et al.

Sci Rep, 2016 Apr 21;6:24697.
PMID: 27098837 DOI: 10.1038/srep24697

Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3.

Matched MeSH terms: Aldosterone/metabolism*
Renin-angiotensin-aldosterone: An inclusive, an invigorative, an interactive and an interminable system

Balakumar P, Anand-Srivastava MB, Jagadeesh G

Pharmacol Res, 2017 11;125(Pt A):1-3.
PMID: 28711403 DOI: 10.1016/j.phrs.2017.07.003
Matched MeSH terms: Aldosterone/metabolism*
Primary aldosteronism: molecular medicine meets public health

Azizan EAB, Drake WM, Brown MJ

Nat Rev Nephrol, 2023 Dec;19(12):788-806.
PMID: 37612380 DOI: 10.1038/s41581-023-00753-6

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.

Matched MeSH terms: Aldosterone/metabolism
Fulltext Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production

Wu X, Azizan EAB, Goodchild E, Garg S, Hagiyama M, Cabrera CP, et al.

Nat Genet, 2023 Jun;55(6):1009-1021.
PMID: 37291193 DOI: 10.1038/s41588-023-01403-0

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.

Matched MeSH terms: Aldosterone
Fulltext Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause

Zhou J, Azizan EAB, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, et al.

Nat Genet, 2021 Sep;53(9):1360-1372.
PMID: 34385710 DOI: 10.1038/s41588-021-00906-y

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.

Matched MeSH terms: Aldosterone/biosynthesis*
Spot urine potassium as a potential screening test for aldosterone breakthrough

Sakthiswary R, Wong M, Isa ZM, Nor Azmi K

Clin Ter, 2012;163(3):195-8.
PMID: 22964690

Treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may suppress aldosterone production only in the initial phase of treatment and subsequently lead to a rising level of aldosterone to baseline or higher. This phenomenon is described as aldosterone breakthrough. Apart from serial plasma aldosterone levels, there are no other test to identify this condition. The purpose of this study was to evaluate the role of spot urine potassium as a potential screening test for aldosterone breakthrough.

Matched MeSH terms: Aldosterone/metabolism*
Fulltext Influence and implications of the renin-angiotensin-aldosterone system in obstructive sleep apnea: An updated systematic review and meta-analysis

Loh HH, Lim QH, Chai CS, Goh SL, Lim LL, Yee A, et al.

J Sleep Res, 2023 Feb;32(1):e13726.
PMID: 36104933 DOI: 10.1111/jsr.13726

Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin-angiotensin-aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality. We aimed to analyse the influence and implications of renin-angiotensin-aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04-0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05-60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11-7.27], p

Matched MeSH terms: Aldosterone
ISH ADA-04 TRANSCRIPTOME PATHWAY ANALYSIS OF AUTONOMOUS AND PHYSIOLOGICAL ALDOSTERONE-PRODUCING HUMAN TISSUE

Zhou J, Lam B, Neogi S, Yeo G, Azizan E, Brown M

J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e40.
PMID: 27753883

Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.

Matched MeSH terms: Aldosterone
LBOS 02-06 HISTOPATHOLOGICAL-SPECIFIC MUTATION SPECTRUM OF ALDOSTERONE-PRODUCING ADENOMAS

Azizan E, Sukor N, Kamaruddin NA, Jamal AR, Ceral J, Solar M, et al.

J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e550.
PMID: 27754305

Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]. This prospective study aim to to characterize the histopathological-specific mutation spectrum of APAs.

Matched MeSH terms: Aldosterone
[OP.3A.01] THE COMPARISON OF THE TRANSCRIPTOME PROFILE OF THE AUTONOMOUS AND THE PHYSIOLOGICAL ALDOSTERONE-PRODUCING TISSUE, THE ALDOSTERONE-PRODUCING ADENOMA AND THE ZONA GLOMERULOSA

Zhou J, Lam BY, Neogi SG, Yeo GS, Teo AE, Maniero C, et al.

J Hypertens, 2016 Sep;34 Suppl 2:e26.
PMID: 27508643 DOI: 10.1097/01.hjh.0000491398.48468.bf

Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). We recently performed a microarray assay using 21 pairs of zona glomerulosa (ZG) and zona fasciculata (ZF), and 14 paired APAs. This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.

Matched MeSH terms: Aldosterone

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