Search Results (44)

Background: Primary aldosteronism is characterized by elevated aldosterone levels, leading to adverse effects such as hypertension, hypokalaemia and increased risk for cardiovascular and cerebrovascular events. Aldosterone impacts the central nervous system by promoting vascular remodelling and oxidative stress, potentially impairing cognitive function. The presence of mineralocorticoid receptors in the hippocampus, a key region for cognition, further suggest a link between primary aldosteronism and cognitive dysfunction. This study aims to further explore the association between hyperaldosteronism and cognitive impairment. Methods: In this pilot study we examined 15 individuals with primary aldosteronism and arterial hypertension alongside 15 age- and sex-matched controls with essential hypertension, all free of previous cerebrovascular events. Clinical and archival laboratory data were obtained. Cognitive function was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results: Participants with primary aldosteronism had higher blood pressure values, longer duration of hypertension, lower serum potassium levels and higher 24 h urine albumin excretion rate compared to controls. Comorbidities, other characteristics and laboratory values were comparable across the two groups. No differences were observed in Mini-Mental State Examination scores, but Montreal Cognitive Assessment scores were significantly lower in the primary aldosteronism group (25.1 ± 2.2 vs. 27.1 ± 2.2, p = 0.021). Trends of poorer performance in language and attention/executive function domains were noted in primary aldosteronism individuals, as well as a higher number of pathological Montreal Cognitive Assessment scores (7 vs. 3). No significant correlations were found between cognitive test results and aldosterone concentrations or blood pressure in primary aldosteronism group. However, importantly, multiple regression analysis showed that aldosterone levels have a significant impact on Montreal Cognitive Assessment test, independent of blood pressure or duration of hypertension. Conclusions: This study supports an association between hyperaldosteronism and cognitive dysfunction, underscoring the need for more active detection and targeted treatment of primary aldosteronism. These findings warrant further research in larger cohorts to better elucidate this relationship. Full article

Aldosterone, a mineralocorticoid hormone synthesised in the adrenal cortex, is essential for maintaining electrolyte balance and fluid homeostasis. Its role in feline physiology remains underexplored, despite its importance in regulating sodium reabsorption and potassium excretion via mineralocorticoid receptors in renal tubules. This study is warranted given aldosterone’s importance in cats, particularly in light of their unique physiological traits, including highly concentrated urine and sensitivity to hydration status. Primary hyperaldosteronism, the most common feline adrenocortical disorder, contributes to arterial hypertension and chronic kidney disease, yet often remains underdiagnosed due to overlapping symptoms like hypokalaemia and hypertension. This research aimed to validate a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to measure serum aldosterone and to establish a reference interval in a population of healthy cats across a broad age range. The method demonstrated high precision and accuracy, with inter-assay coefficients of variation under 15%. Analysis of 49 healthy cats (40 young, 9 old) revealed a reference interval of 5.0–78.4 pg/mL (13.8–217.2 pmol/L). These findings provide a robust framework for diagnosing aldosterone-related disorders in cats and underscore the need for species-specific diagnostic tools. Improved understanding of aldosterone’s role could refine treatment strategies and enhance outcomes for affected feline patients. Full article

Hypertension remains a global health challenge due to its high prevalence and association with premature morbidity and mortality. Aldosterone, a mineralocorticoid hormone, and its receptor, the mineralocorticoid receptor (MR), are highly implicated in hypertension pathogenesis. Aldosterone synthase is the sole enzyme responsible for producing aldosterone in humans. We established transgenic mice carrying the human aldosterone synthase gene (cyp11B2) and showed dramatically increased levels of aldosterone in female hemizygotes. High-salt diets persistently increased blood pressure in these mice, and salt-induced hypertension was significantly ameliorated by reducing aldosterone levels via an aldosterone synthase inhibitor or blocking MR via an MR inhibitor. Since both hypertension and hyperaldosteronism specifically induce chronic kidney disease, in this model, we demonstrated that chronic high-salt diets induced hypertension in this mouse line and resulted in kidney inflammation and injury. Both the aldosterone synthase inhibitor and the MR antagonist markedly blocked high-salt-diet-mediated kidney injury. Thus, this transgenic mouse line can be used to study the pathogenic mechanisms underlying aldosterone and its receptor and to screen therapeutic compounds for aldosterone-mediated hypertension and related complications, such as kidney disease, in humans. Full article

Objectives: To assess success rates and cost-effectiveness of adrenal venous sampling (AVS) after implementing point-of-care rapid cortisol (RC) testing conducted using a europium nanoparticle-based fluoro-immunoassay in patients with primary hyperaldosteronism. Methods: A retrospective review of AVS procedures was conducted at our medical center between January 2016 and June 2024. The primary objective was to compare the success rates of AVS before and after the implementation of the RC testing. Secondary outcomes included a cost–benefit analysis. Results: Of 55 AVS procedures, 19 were conducted using RC testing and 36 were in the historical control cohort. The success rates for right vein sampling were 79% and 67%, respectively. Overall, in six (31.5%) patients in the RC cohort, a low RC selectivity index (SI) value, calculated within 10 min, enabled determination of unsuccessful cannulation and need for resampling during the same AVS session. Repeated sampling resulted in successful procedures in two cases (10.5%) and unsuccessful AVS in four cases, nonetheless sparing the need for repeated AVS sessions in 31.5% of cases. Utilizing RC potentially spared 6 patients from repeated AVS sessions, and considering the additional expenses on the RC test, its use afforded cost savings of an average of $1288 per patient. Conclusions: We demonstrated the cost-effectiveness of utilizing RC measurement in sparing the need for repeated AVS sessions. RC measurement during AVS enabled identification of correct catheter placement in real time, allowing for prompt decisions regarding the need for additional sampling attempts, thereby reducing subsequent costs of repeated AVS sessions. Full article

Background and Clinical Significance: Licorice (glycyrrhiza glabra) cough syrup intoxication is manifested with refractory hypokalemia, hypertension, and metabolic alkalosis. The transformation of glycyrrhiza glabra metabolic into glycyrrhetic acid after ingestion further inhibits the 11-β-hydroxysteroid dehydrogenase-2 enzyme, impeding the conversion of cortisol into cortisone. The accumulation of cortisol can also stimulate mineralocorticoid receptors, which leads to a pseudo-hyperaldosteronism-like effect. Case Presentation: We report a 60-year-old male patient with licorice intoxication due to the chronic consumption of licorice cough syrup. He exhibited a transient seizure lasting approximately one minute. Initially, hypokalemia (potassium level was 2.0 mmol/L), metabolic alkalosis, and QT interval prolongation with premature ventricular complexes were demonstrated on his electrocardiogram. Despite the administration of both intravenous and oral potassium supplements over two days, there was no significant improvement in hypokalemia. Spironolactone, an aldosterone receptor antagonist, was administered in addition to ongoing potassium supplementation from the 3rd day. This intervention led to a rapid normalization of hypokalemia in one day. The patient was ultimately discharged on the 6th day without any subsequent complications. Conclusions: The licorice-induced chronic intoxication, which led to pseudo-hyperaldosteronism and refractory hypokalemia, was successfully managed with aggressive potassium supplementation and spironolactone treatment. Full article

Background: Adrenal tumors are a common finding in clinical practice, and only detailed evaluation may reveal secretory and metabolic abnormalities or their malignant character. We aimed to highlight epidemiological data, rates of malignancy, clinical or secretory characteristics, and the cardiometabolic implications of adrenal masses. Methods: We conducted a retrospective analysis using data from the medical files of 474 patients with adrenal pathology hospitalized between January 2007 and January 2020, before the COVID-19 pandemic, using the ICD-10 codes. After applying inclusion and exclusion criteria, a total of 264 patients with adrenal tumors were enrolled in the study. Patients underwent clinical examination, abdominal imaging, and hormonal evaluation, and some of them underwent a pathological exam after adrenalectomy. Results: Median age at diagnosis was 56 (17) years, with 81.06% of patients being female. The median follow-up period was 41.5 (70) months, ranging from 6 months to 13 years. Adrenal tumors were most frequently seen in older female patients, with 83.47% of them being over 40 years old. The malignancy rate was 4.54%. Hormonally nonfunctioning tumors (71.95%) predominated, and overt hypercortisolism was present in 10.61% of patients, as was mild autonomous cortisol secretion in 5.31% of patients, primary hyperaldosteronism in 8.71% of patients, and adrenal paraganglioma in 3.41% of patients. Cardiometabolic comorbid conditions were similar in patients with functioning and nonfunctioning tumors. Conclusions: All patients with adrenal tumors should receive a complete hormonal workup and detailed malignancy risk assessment. Even though a hormonally active tumor predisposes to cardiometabolic comorbid conditions, a nonfunctioning lesion may also be associated with such disorders and needs thorough assessment. Full article

Quantitative systems pharmacology (QSP) models are rarely applied prospectively for decision-making in clinical practice. We therefore aimed to operationalize a QSP model for potas-sium homeostasis to predict potassium trajectories based on spironolactone administrations. For this purpose, we proposed a general workflow that was applied to electronic health records (EHR) from patients treated in a German tertiary care hospital. The workflow steps included model exploration, local and global sensitivity analyses (SA), identifiability analysis (IA) of model parameters, and specification of their inter-individual variability (IIV). Patient covariates, selected parameters, and IIV then defined prior information for the Bayesian a posteriori prediction of individual potassium trajectories of the following day. Following these steps, the successfully operationalized QSP model was interactively explored via a Shiny app. SA and IA yielded five influential and estimable parameters (extracellular fluid volume, hyperaldosteronism, mineral corticoid receptor abundance, potassium intake, sodium intake) for Bayesian prediction. The operationalized model was validated in nine pilot patients and showed satisfactory performance based on the (absolute) average fold error. This provides proof-of-principle for a Prescribing Monitoring of potassium concentrations in a hospital system, which could suggest preemptive clinical measures and therefore potentially avoid dangerous hyperkalemia or hypokalemia. Full article

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5–10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism. Full article

Background: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. Methods: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. Results: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. Conclusions: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice. Full article

Abnormalities in G-protein-gated inwardly rectifying potassium (GIRK) channels have been implicated in diseased states of the cardiovascular system; however, the role of GIRK4 (Kir3.4) in cardiac physiology and pathophysiology has yet to be completely understood. Within the heart, the K_ACh channel, consisting of two GIRK1 and two GIRK4 subunits, plays a major role in modulating the parasympathetic nervous system’s influence on cardiac physiology. Being that GIRK4 is necessary for the functional K_ACh channel, KCNJ5, which encodes GIRK4, it presents as a therapeutic target for cardiovascular pathology. Human variants in KCNJ5 have been identified in familial hyperaldosteronism type III, long QT syndrome, atrial fibrillation, and sinus node dysfunction. Here, we explore the relevance of KCNJ5 in each of these diseases. Further, we address the limitations and complexities of discerning the role of KCNJ5 in cardiovascular pathophysiology, as identical human variants of KCNJ5 have been identified in several diseases with overlapping pathophysiology. Full article

The renin angiotensin aldosterone system is a key regulator of blood pressure. Aldosterone is the final effector of this pathway, acting predominantly via mineralocorticoid receptors. Aldosterone facilitates the conservation of sodium and, with it, water and acts as a powerful stimulus for potassium excretion. However, evidence for the pathological impact of excess mineralocorticoid receptor stimulation is increasing. Here, we discussed how in the heart, hyperaldosteronism is associated with fibrosis, cardiac dysfunction, and maladaptive hypertrophy. In the kidney, aldosterone was shown to cause proteinuria and fibrosis and may contribute to the progression of kidney disease. More recently, studies suggested that aldosterone excess damaged endothelial cells. Here, we reviewed how damage to the endothelial glycocalyx may contribute to this process. The endothelial glycocalyx is a heterogenous, negatively charged layer on the luminal surface of cells. Aldosterone exposure alters this layer. The resulting structural changes reduced endothelial reactivity in response to protective shear stress, altered permeability, and increased immune cell trafficking. Finally, we reviewed current therapeutic strategies for limiting endothelial damage and suggested that preventing glycocalyx remodelling in response to aldosterone exposure may provide a novel strategy, free from the serious adverse effect of hyperkalaemia seen in response to mineralocorticoid blockade. Full article

Aldosterone, a vital hormone of the human body, has various pathophysiological roles. The excess of aldosterone, also known as primary aldosteronism, is the most common secondary cause of hypertension. Primary aldosteronism is associated with an increased risk of cardiovascular disease and kidney dysfunction compared to essential hypertension. Excess aldosterone can lead to harmful metabolic and other pathophysiological alterations, as well as cause inflammatory, oxidative, and fibrotic effects in the heart, kidney, and blood vessels. These alterations can result in coronary artery disease, including ischemia and myocardial infarction, left ventricular hypertrophy, heart failure, arterial fibrillation, intracarotid intima thickening, cerebrovascular disease, and chronic kidney disease. Thus, aldosterone affects several tissues, especially in the cardiovascular system, and the metabolic and pathophysiological alterations are related to severe diseases. Therefore, understanding the effects of aldosterone on the body is important for health maintenance in hypertensive patients. In this review, we focus on currently available evidence regarding the role of aldosterone in alterations of the cardiovascular and renal systems. We also describe the risk of cardiovascular events and renal dysfunction in hyperaldosteronism. Full article

Catheterization of the right adrenal vein (rt.AdV) to obtain blood samples can often be difficult. The aim of the present study was to investigate whether blood sampling from the inferior vena cava (IVC) at its juncture with the rt.AdV can be an ancillary to sampling of blood directly from the rt.AdV. This study included 44 patients diagnosed with primary aldosteronism (PA) in whom AVS with adrenocorticotropic hormone (ACTH) was performed, resulting in a diagnosis of idiopathic hyperaldosteronism (IHA) (n = 24), and patients diagnosed with unilateral aldosterone-producing adenoma (APA) (n = 20; rt.APA = 8, lt.APA = 12). In addition to regular blood sampling, blood was also sampled from the IVC, as the substitute rt.AdV [S-rt.AdV]. Diagnostic performance with the conventional lateralized index (LI) and the modified LI using the S-rt.AdV were compared to examine the utility of the modified LI. The modified LI of the rt.APA (0.4 ± 0.4) was significantly lower than those of the IHA (1.4 ± 0.7) (p < 0.001) and the lt.APA (3.5 ± 2.0) (p < 0.001). The modified LI of the lt.APA was significantly higher than those of the IHA (p < 0.001) and rt.APA (p < 0.001). Likelihood ratios to diagnose rt.APA and lt.APA using the modified LI with threshold values of 0.3 and 3.1 were 27.0, and 18.6, respectively. The modified LI has the potential to be an ancillary method for rt.AdV sampling in cases in which rt.AdV sampling is difficult. Obtaining the modified LI is extremely simple, which might complement conventional AVS. Full article

In recent years, research has emphasized the significance of mild clinical and biochemical presentations of primary aldosteronism (PA) that do not meet current diagnostic criteria of the syndrome. In this study, we assessed the prevalence of autonomous aldosterone (Ald) secretion (AAS), defined as a positive (>1.2 ng/dL/mIU/L) Ald-to-renin ratio (ADRR) combined with unsuppressed Ald (>4 ng/dL), and its associations with blood pressure (BP), cardiac function, and common carotid artery (CCA) intima-media thickness (IMT) in patients with incidentally discovered adrenal adenomas (AI), who were either normo- or hypertensive but had no other cardiovascular disease. Among 332 AI patients hospitalized between November 2018 and December 2019, 63 study participants were recruited (26 normo- and 37 hypertensive), who underwent hormonal examinations, 24 h ambulatory BP measurement, transthoracic echocardiography, and CCA IMT assessment without altering chronic medications. AAS was found in approximately 25% of subjects (seven normo- and nine hypertensive); urinary aldosterone excretion (UAldE) exceeded 10 ug/day in none of the subjects. The left ventricular mass index correlated positively with UAldE in non-diabetic patients (n = 50), and negatively with renin in those without beta blocker therapy (n = 38). The study shows that a pragmatic approach to hormonal assessment (no chronic therapy modification) may reveal patients with AAS. Screening for this subclinical PA presentation is probably more effective with a permissive ADRR than UAldE in such a setting. Full article

Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 α₁-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3_S), whereas a loss of ion channel function was seen in the long (Cav1.3_L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3_S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3_L variant results in sinus node dysfunction. Full article