Introduction: Primary aldosteronism (PA), most commonly caused by aldosterone-producing adenomas (APAs), represents the leading form of surgically curable secondary hypertension. While genomic studies have elucidated the mutational landscape of APAs, the spatial organisation and functional role of immune populations across APAs, aldosterone-producing micronodules (APMs), and adjacent adrenal cortex remain poorly defined at single-cell resolution. Methodology: Single-cell RNA sequencing (scRNA-seq) was integrated with spatial transcriptomics in APAs and paired adjacent adrenal cortex, complemented by immunohistochemical (IHC) validation. Immune populations were spatially mapped using canonical markers (CD14, CD68, CD163, HLA-DR, CD8A, and CD4) across defined adrenocortical regions. Results: The adrenal microenvironment in PA demonstrates structured immune organisation rather than passive infiltration. CD14+ monocyte-lineage cells localize intraparenchymally within APAs (n = 10), intercalating between CYP11B2+ aldosterone-producing cells and forming a pattern distinct from perivascular immune niches. scRNA-seq further identified a transcriptionally distinct CD14+ population within the zona reticularis (zR) that co-expresses steroidogenic markers (CYB5A, SULT2A1, TSPAN12) while lacking canonical monocyte transcripts. IHC supported this observation, demonstrating CD14 expression within adrenocortical zR parenchymal cells (n = 5). In parallel, CD4 and HLA-DRA exhibited diffuse cytoplasmic staining within zR parenchymal cells in the absence of classical macrophage marker coexpression (CD68), suggesting non-canonical or context-dependent expression within steroidogenic compartments. CD68+ and CD163+ macrophages were sparsely distributed across APA, APM and adjacent cortex, consistent with lowdensity tissue-resident populations, while CD8A+ cytotoxic lymphocytes were enriched in APAs and APMs with diffuse parenchymal cytoplasmic staining of CD8A additionally observed within the zR. Conclusion These findings reveal a previously unrecognized spatially organised immune-steroidogenic interface within the adrenal cortex. The presence of immune-associated transcriptional and protein signatures within zR cells suggests potential functional plasticity of steroidogenic cells, possibly extending to antigen presentation-related pathways, warranting further mechanistic investigation
Hyperaldosteronism ; Humans

This review examines strategies for the prevention and management of obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia, conditions that are increasing in Singapore, as components of individualised health plans in 'Healthier SG' and beyond. We describe cardiometabolic disease prevention and management initiatives in Changi General Hospital (CGH), including collaborations with SingHealth Polyclinics, Active SG, Exercise is Medicine Singapore and community partners in the Eastern Community Health Outreach programme, and highlight advances in curable hypertension (e.g., primary hyperaldosteronism) and novel cardiovascular risk markers such as lipoprotein(a). We also outline technology-based interventions, notably the CGH Health Management Unit, which demonstrate the utility and convenience of telemedicine, and digital therapeutics in the form of apps that have been shown to improve treatment adherence and clinical outcomes. Individual empowerment, in partnership with community and healthcare providers and supported by research and innovation of care delivery, is key to building a healthier and stronger nation.
Humans ; Singapore ; Diabetes Mellitus, Type 2/therapy* ; Hypertension/therapy* ; Obesity/therapy* ; Dyslipidemias/therapy* ; Telemedicine ; Cardiovascular Diseases/prevention & control* ; Exercise ; Metabolic Diseases/prevention & control*

Humans ; Proton Pump Inhibitors/therapeutic use* ; Deprescriptions

Adrenal Glands ; Humans ; Hyperaldosteronism ; Retrospective Studies ; Singapore

Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately.
Aldosterone ; blood ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Aortic Coarctation ; complications ; diagnosis ; Blood Pressure ; Glomerulonephritis ; complications ; diagnosis ; Humans ; Hyperaldosteronism ; diagnosis ; Hypertension ; complications ; diagnosis ; therapy ; Primary Health Care ; methods ; Referral and Consultation ; Renal Artery Obstruction ; drug therapy ; Renin ; blood ; Sleep Apnea, Obstructive ; complications