Aldosterone synthase inhibition: a novel bullet to fight cardiovascular-kidney metabolic syndrome.

Aldosterone is synthesized by the CYP11B2 enzyme, primarily in the zona glomerulosa of the adrenal gland. It exerts its classical effects on sodium and water balance in the renal distal nephron through binding to the mineralocorticoid receptor (MR). Excess aldosterone production or overactivation of the MR outside the distal nephron leads to cardiac, renal, and vascular injury by increasing oxidative stress and activating the inflammatory and fibrotic pathways.

Patient-derived organoids reveal hypoxia-driven plasticity and therapeutic vulnerabilities in pheochromocytomas and paragangliomas.

Unlabelled: Pheochromocytomas and paragangliomas (PPGLs) are rare chromaffin cell-derived neuroendocrine tumors of sympathetic (catecholamine-producing) or parasympathetic (nonsecretory) origin, frequently driven by dysregulation of hypoxia-inducible factor (HIF) signaling, particularly HIF-2α. Although often benign, PPGLs can metastasize unpredictably, with limited therapeutic options once disseminated. Progress has been hindered by the lack of robust preclinical models, especially those that capture their molecular complexity and microenvironmental influences.

Discordance and shortcomings of aldosterone suppression tests in primary aldosteronism.

Background: The saline suppression test (SST) and the captopril challenge test (CCT) have traditionally been used to confirm or exclude primary aldosteronism (PA). New guidelines recommend using these tests to predict the likelihood of unilateral PA. This study evaluated the diagnostic accuracy, consistency, and clinical implications of these tests.

The Aldosteronoma Resolution Score as a Predictive Metric for Outcomes after Radiofrequency Ablation for Primary Aldosteronism.

Purpose: Radiofrequency ablation (RFA) is an emerging treatment for treatment primary aldosteronism (PA). The Aldosteronoma Resolution Score (ARS) is a validated metric for prognostication of complete clinical response after adrenalectomy. The purpose of this study is to validate ARS as a prognosticator for outcomes post-RFA.

Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline.

Background: Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension. It is associated with an increased risk of cardiovascular complications compared with primary hypertension. Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated.

Subclinical Primary Aldosteronism and Major Adverse Cardiovascular Events: A Longitudinal Population-Based Cohort Study.

Background: Primary aldosteronism (PA), an overt form of renin-independent aldosterone production, leads to a disproportionately high rate of major adverse cardiovascular events (MACEs). Mounting evidence suggests that milder forms of renin-independent aldosterone production (subclinical PA) are highly prevalent; however, the link between subclinical PA and MACE remains uncertain.

Methods: This prospective study included 2017 Canadian adults 40 to 69 years of age from the randomly sampled, population-based CARTaGENE cohort (Québec, Canada), in which aldosterone and renin concentrations at enrollment (2009-2010) were measured.

Potassium Dysregulation in Patients with CKD: Time to Focus on Low Potassium Intake and Hypokalemia.

Hyperkalemia has long been the focus of potassium (K+) dysregulation in patients with chronic kidney disease (CKD). However, while the risks of hyperkalemia are well known and clearly important, there is growing evidence that hypokalemia occurs at least as frequently in those with CKD and is associated with an increase in all cause or cardiovascular (CV) mortality as well as a faster progression of renal disease and earlier requirement for kidney replacement therapy (KRT). This is a brief review of low K+ intake and hypokalemia in patients with CKD.

The Evolution of Primary Aldosteronism and the Role of Norrin.

Primary aldosteronism (PA) is renin-independent aldosterone production that causes hypertension and cardiovascular disease. We investigated the proteomic evolution of PA from normotensive people with renin-independent aldosteronism to those with overt PA. The PA plasma proteome was characterized by pathways related to cardiovascular disease (inflammation, energy/redox, vascular remodeling).

Proteomic signatures to detect unilateral primary aldosteronism in hypertensive patients.

Context: Primary aldosteronism (PA) is a major cause of hypertension and cardiovascular disease; however, diagnosing PA remains challenging.

Objective: We investigated whether deep proteomic analyses could be used to diagnose unilateral PA in hypertensive patients.

Methods: We enrolled 52 patients with unilateral PA and 46 with essential hypertension (EH) and divided them into training and validation cohorts.

Real-world outcomes of finerenone in primary aldosteronism.

Primary aldosteronism (PA) treatment with mineralocorticoid receptor antagonists (MRAs) is effective but limited by side-effects and low potency of currently available options. Finerenone, a novel MRA, has emerged as a promising alternative but data in PA are lacking. This report presents a real-world study wherein PA patients on eplerenone were forced to switch to finerenone therapy during a national shortage.

Mineralocorticoid Receptor Antagonist Use in Hypertension to Prevent Heart Failure.

Mineralocorticoid receptor antagonists (MRAs) reduce cardiovascular mortality and heart failure (HF) hospitalizations across the spectrum of HF. Beyond their recognized benefits in patients with established HF, the value of MRA therapy may be undervalued for the prevention of HF in patients with hypertension. Emerging evidence indicates that a substantial proportion of patients considered to have "idiopathic" or "essential" hypertension have mineralocorticoid receptor overactivation by under-recognized mechanisms (such as, primary aldosteronism pathophysiology, cortisol dysregulation, and ligand-independent activation).

The Impact Of Modern Industrialized Dietary Sodium Intake On The Plasma Proteome.

Background: High dietary sodium intake is associated with cardiovascular disease. We investigated the influence of sodium intake on the plasma proteome.

Methods: Prospectively recruited normotensive participants underwent 2 controlled dietary sodium interventions to evaluate hormonal and proteomic (1,512 proteins) changes: sodium-restriction resembling ancestral hunter-gatherer intake (~10 mEq/day, ~230mg/day) and sodium-loading resembling modern industrialized intake (~200 mEq/day, ~4600mg/day).

ACE Inhibition to Distinguish Low-Renin Hypertension From Primary Aldosteronism.

Background: Primary aldosteronism (PA) is a distinct cause of low-renin hypertension (LRH), characterized by inappropriate aldosterone production. We investigated the distinction between LRH and PA by leveraging the physiological effects of angiotensin-converting enzyme inhibition.

Methods: We conducted a retrospective cohort study including 756 patients with LRH who underwent a captopril challenge test (CCT) for evaluation of PA.

Subclinical Primary Aldosteronism is Characterized by Maladaptive Natriuretic Peptide and Adrenal Hormonal Physiology.

Background: A continuum of non-suppressible aldosterone production has been demonstrated in normotensive individuals, termed subclinical primary aldosteronism (PA), and is consistently associated with increased risk for developing hypertension and cardiovascular disease. The hormonal mechanisms accounting for subclinical PA are not well understood.

Method: To quantify the magnitude of subclinical PA, prospectively recruited normotensive participants (n=75) had their maximally suppressed plasma aldosterone assessed after maintaining supine posture following an oral sodium loading protocol.

Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program.

Background: Primary aldosteronism, an endocrinopathy present in ≥10% to 25% of patients with hypertension, confers excess cardiovascular risk that can be mitigated with aldosterone-directed therapy. However, only 2% of eligible patients undergo guideline-recommended screening. This study aimed to bypass clinical inertia and identify people with primary aldosteronism using pragmatic, direct-to-patient testing.

Mild autonomous cortisol secretion in patients with aldosterone-producing adenoma and risk for cardiac remodeling and diastolic dysfunction.

Background: Mild autonomous cortisol secretion (MACS) is common in adrenal adenomas, including patients with primary aldosteronism (PA) with aldosterone-producing adenomas (APA). This study investigated the impact of MACS on cardiac remodeling and diastolic dysfunction in patients with APA.

Methods: We prospectively enrolled 483 patients with APA.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.