Primary aldosteronism (PA) and obstructive sleep apnea (OSA) are common but often unrecognized contributors to hypertension. When they coexist, aldosterone excess, fluid redistribution, intermittent hypoxia, sympathetic activation, and shared metabolic risk may increase hypertension-mediated organ damage. This narrative review examines the evidence linking PA and OSA, with emphasis on mechanisms, cardiovascular and renal consequences, diagnostic limitations, and clinical management. Aldosterone-related sodium retention and nocturnal rostral fluid shift may worsen upper-airway obstruction. Conversely, intermittent hypoxia, sleep fragmentation, and sympathetic activation in OSA may alter renin-angiotensin-aldosterone system activity, although OSA does not account for autonomous aldosterone secretion. Both disorders are associated with oxidative stress, inflammation, endothelial dysfunction, cardiac remodeling, and renal injury. Their overlap should be considered in patients with resistant hypertension, hypokalemia, adrenal incidentaloma, clinically suspected OSA, or organ damage not fully explained by measured blood pressure. Management requires independent confirmation of each disorder, subtype-directed PA treatment with adrenalectomy or mineralocorticoid receptor antagonists, and appropriate OSA treatment with positive airway pressure or other individualized measures. Multidisciplinary care may improve blood pressure and intermediate organ outcomes, but prospective studies are needed to determine whether combined treatment reduces long-term cardiovascular, renal, and cerebrovascular events.

Orthostatic intolerance (OI) is characterized by the inability to maintain an upright posture without experiencing severe signs and symptoms, including hypotension, palpitations, light-headedness, pallor, fatigue, weakness, dizziness, impaired concentration, tremulousness, and nausea. The majority of patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) exhibit OI, which is the primary factor restricting daily functional capacity. During an upright posture, approximately 800 mL of blood is translocated from the intrathoracic venous compartment to the veins of the buttocks, pelvis, and legs. Under normal conditions, compensatory cardiovascular responses to this orthostatic stress include activation of the muscle pump through calf muscle contraction and a neurogenically mediated increase in heart rate and in systemic vascular resistance. The majority of the symptoms of OI are believed to be cardiovascular and related to reduced cerebral blood flow and excessive activation of the sympathetic nervous system. However, compensatory sympathetic activation is essential for maintaining orthostasis. Many patients have a small left ventricle and associated low cardiac output. In addition, both the renin-aldosterone and antidiuretic hormone systems that regulate circulatory blood volume were downregulated. Postural stability is necessary for maintaining the static balance critical for performing many daily activities. Recently studies have reported that postural instability or disequilibrium, potentially associated with central vestibular dysfunction, should be considered to be involved in the pathogenesis of OI among patients with ME/CFS. Disequilibrium should be recognized as an important cause of OI in those patients.

Primary aldosteronism (PA) is the most common curable cause of secondary hypertension and an independent risk factor for chronic kidney disease (CKD). This review focuses on the pathophysiological mechanisms of aldosterone-induced renal injury, including mineralocorticoid receptor activation, nongenomic signaling via GPER, oxidative stress, and the upregulation of profibrotic and inflammatory mediators such as TGF-β1, NF-κB, and NLRP3. Chronic aldosterone excess leads to podocyte injury, microvascular dysfunction, and interstitial fibrosis, resulting in decreased glomerular filtration rate and CKD progression.Genetic mutations (KCNJ5, ATP1A1, CACNA1D) and tubular stress biomarkers (L-FABP, KIM-1, microalbuminuria) are discussed as key factors of early nephron injury. Comparative clinical data show that adrenalectomy provides superior nephroprotection compared to pharmacological blockade, while long-term therapy with mineralocorticoid receptor antagonists requires careful renal monitoring. Emerging therapeutic strategies, including nonsteroidal MR antagonists and aldosterone synthase inhibitors (baxdrostat), offer new prospects for targeted nephroprotection.By integrating molecular and clinical evidence, this review highlights the central role of aldosterone in renal pathology and emphasizes early detection and personalized treatment approaches to prevent CKD progression in patients with PA.

Compound glycyrrhizin tablets, derived from licorice root, are widely used for their anti-inflammatory and hepatoprotective properties. However, their active metabolite, glycyrrhetinic acid, can induce acquired apparent mineralocorticoid excess (AME) - a clinical syndrome where cortisol abnormally activates mineralocorticoid receptors due to the inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), mimicking primary aldosteronism. We report a case of a 57-year-old male who developed severe hypertension and hypokalemia after 30 days of treatment with compound glycyrrhizin (150 mg, t.i.d.). Laboratory investigations revealed profound hypokalemia (2.03 mmol/L) and metabolic alkalosis. Critically, both plasma renin activity (< 0.5 μIU/mL) and aldosterone levels (2.4 - 2.7 ng/dL) were significantly suppressed, effectively ruling out primary and secondary hyperaldosteronism. A diagnosis of acquired AME was established based on the temporal relationship with glycyrrhizin intake, the "double-low" hormonal profile, and the exclusion of Cushing's syndrome. Following treatment with amlodipine and potassium supplementation, the patient's symptoms resolved. At the 2-week post-discharge follow-up, after discontinuing all medications, his blood pressure remained stable (< 140/90 mmHg) and serum potassium normalized to 4.55 mmol/L, confirming the reversible nature of acquired AME.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome encompassing hypertensive left ventricular remodelling with diastolic dysfunction and systemic inflammation-driven endothelial dysfunction, with possible contributions from visceral adipose tissue-associated metabolic and proinflammatory alterations. However, conventional key risk factors for HFpEF, including advanced age, female sex, obesity, diabetes, and chronic kidney disease, are closely associated with mineralocorticoid receptor (MR) overactivation through several under-recognized mechanisms, i.e. renin-independent aldosterone excess, cortisol dysregulation, and ligand-independent activation. MR overactivation promotes myocardial hypertrophy and fibrosis, vascular remodelling, and systemic inflammation, all of which are hallmark features of HFpEF. Among patients with HFpEF, the steroidal MR antagonist (MRA) spironolactone has been suggested to reduce the risk of HF-related events, while the non-steroidal MRA finerenone has significantly reduced the primary composite of total worsening HF events and cardiovascular death. Across subgroups suggestive of MR overactivation, MRA therapy has shown generally consistent efficacy and safety, although greater adiposity may be associated with greater MRA efficacy. Given the continuum of MR activation across HF stages, early therapeutic intervention targeting MR overactivation may mitigate the risk of HFpEF development and progression. Furthermore, aldosterone synthase inhibitors and MR modulators, which also attenuate MR overactivation, are being evaluated for HFpEF prevention and treatment. This paper presents the mechanistic pathways linking MR overactivation to HFpEF and highlights the potential benefits of mitigating MR activation for its prevention and treatment, calling for renewed consideration of treatment strategies in clinical practice and trial design.

Primary aldosteronism (PA) is a common cause of secondary hypertension. Bilateral macronodular adrenocortical disease (BMAD) with ARMC5 mutations is classically associated with hypercortisolism. This report describes a 54-year-old female with hypertension and hypokalemia, biochemically confirmed as PA, and imaging showing bilateral adrenal macronodules. Postoperative peripheral blood genetic testing identified a germline ARMC5 frameshift insertion (c.337dup). Whole-exome sequencing of the resected adrenal tissue revealed an additional somatic frameshift deletion (c.277_316del, p. P93fs, VAF 43.1%) absent in blood, demonstrating biallelic ARMC5 inactivation. Following unilateral adrenalectomy, the patient's aldosterone levels normalized. This case shows that ARMC5 mutations can cause isolated mineralocorticoid excess without hypercortisolism, expanding the known phenotypic spectrum. Genetic testing for ARMC5 should be considered in patients with bilateral adrenal enlargement regardless of steroid hormone profile.

Background: Hyperkalemia (HK) is a common complication of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and the risk is often increased by concomitant use of a mineralocorticoid receptor antagonist (MRA). The effect of SGLT2i co-prescription on this risk in routine clinical practice remains incompletely understood. Methods: This is a secondary analysis of a published retrospective cohort of 905 adult RAASi users attending outpatient clinics at King Abdulaziz Medical City, Jeddah, Saudi Arabia (IRB: NRJ22J/279/11), followed for a median of 28 months. Patients were classified as RAASi alone (n = 723) or RAASi plus MRA (n = 182). Beta-blockers and digoxin were excluded from the exposure definition. Effect modification by SGLT2i was assessed using logistic regression with a multiplicative interaction term. Results: MRA addition was associated with significantly higher rates of any HK (48.4% vs. 28.9%; RR 1.67, 95% CI 1.38-2.02, p < 0.001) and moderate-to-severe HK (13.7% vs. 6.9%; RR 1.99, 95% CI 1.26-3.12, p = 0.003). Overall, RAASi discontinuation rates were similar between groups. SGLT2i co-prescription significantly modified the association between MRA use and HK-driven RAASi discontinuation (interaction p = 0.004): among patients without SGLT2i, MRA addition was associated with a more than 5-fold increase in HK-driven discontinuation (21.1% vs. 4.1%; RR 5.11, p = 0.001), whereas no significant excess risk was observed among SGLT2i users (1.8% vs. 4.2%; RR 0.44, 95% CI 0.12-1.57, p = 0.190), although this subgroup estimate was imprecise. CKD (aOR 2.16, 95% CI 1.56-2.99) and age ≥ 75 years (aOR 1.64, 95% CI 1.04-2.58) were the strongest independent predictors of HK. Conclusions: MRA addition to RAASi substantially increases HK burden, and SGLT2i co-prescription appears to protect against HK-driven RAASi discontinuation in combined RAASi-MRA-treated patients. In patients with established indications for SGLT2i, co-prescription may confer the additional benefit of preserving RAASi continuity in the setting of MRA combination therapy.

Low-renin hypertension is increasingly recognized as a common and clinically important form of hypertension. Expanded screening for primary aldosteronism has revealed many individuals with suppressed renin who do not meet the diagnostic criteria for aldosterone excess, yet exhibit features consistent with sodium retention or increased mineralocorticoid activity. This review synthesizes evidence from targeted literature searches on the epidemiology, mechanisms, diagnostic challenges, and treatment of low-renin hypertension. Early studies proposed renin, in the presence of hypertension, as a marker of excess sodium retention and volume expansion, suggesting that renin could guide individualized therapy. Adoption of a renin-guided treatment approach was historically limited by assay variability and concerns regarding adverse effects from high-dose mineralocorticoid receptor antagonists. However, improvements in renin assay performance, increased accessibility and use of renin testing, and the availability of lower-dose and better-tolerated mineralocorticoid receptor antagonists have renewed interest in this strategy. Low-renin hypertension encompasses primary aldosteronism, conditions that mimic mineralocorticoid excess, and disorders of renal tubular sodium transport. Across this spectrum, patients respond more favorably to therapies targeting sodium retention: mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, or thiazide diuretics, than to agents directed primarily at vasoconstriction. Recognition of low-renin hypertension as a distinct phenotype enables mechanism-based therapy and may improve blood pressure control, reduce medication burden, and mitigate long-term cardiovascular risk.