Primary aldosteronism

Primary aldosteronism is the most common endocrine cause of secondary hypertension, with the 2025 Endocrine Society Clinical Practice Guideline estimating a prevalence of 5% to 14% among hypertensive people seen in primary care and up to 30% in referral centres, rising to a range of 11.3% to 29.1% in resistant hypertension and 28.1% when hypertension is accompanied by hypokalaemia. Despite guideline endorsement of near-universal screening, actual testing is rare: fewer than 1% of a Canadian cohort of one million hypertensive individuals had ever been screened, and a large United States electronic health registry study found that only 2.1% of people meeting criteria for resistant hypertension were screened within two years of becoming eligible. The clinical cost of that gap is real rather than theoretical, since a meta-analysis of 31 studies covering 3,838 people with primary aldosteronism and 9,284 with essential hypertension found significantly higher odds of stroke, coronary artery disease, atrial fibrillation and heart failure, and a separate meta-analysis of 46 studies found higher odds of albuminuria and proteinuria, all over and above the effect of blood pressure itself.

Care follows a screen, confirm, subtype and treat pathway. The guideline suggests screening all individuals with hypertension using the aldosterone to renin ratio, with potassium checked alongside to avoid a false negative from hypokalaemia. A positive screen with an intermediate probability of lateralizing disease can go on to aldosterone-suppression testing, and anyone considering surgery should have adrenal CT plus adrenal vein sampling to decide whether disease is unilateral or bilateral, with a selectivity index above 5:1 confirming successful catheterisation and a lateralization index above 4:1 indicating a dominant side; a minority of young patients under 35 with marked disease and a clear adenoma over 1 cm on CT can skip adrenal vein sampling. Lateralizing disease in a willing surgical candidate is treated with unilateral adrenalectomy, while bilateral disease, or lateralizing disease in someone who cannot or will not have surgery, is treated with a mineralocorticoid receptor antagonist, with spironolactone preferred over other agents for cost and availability and started at 12.5 to 25 mg daily. Every patient with an adrenal adenoma is also suggested to have a 1-mg overnight dexamethasone suppression test to catch co-existing mild autonomous cortisol secretion, reported in roughly 5% to 27% of people with primary aldosteronism depending on the series.

Nuclear medicine's role remains explicitly investigational rather than a guideline recommendation: the 2025 guideline discusses PET-based imaging with aldosterone synthase-specific molecules only under Research Considerations, as a possible way to reduce reliance on adrenal vein sampling and its interventional radiology expertise. Two tracers dominate that literature. Dexamethasone-suppressed 11C-metomidate PET-CT was noninferior to adrenal vein sampling for lateralization in 93 surgically treated patients in the guideline's cited study, but an independent prospective head-to-head series found its concordance with adrenal vein sampling was only 51%, no better than adrenal CT at 53%, and practical use is limited by the short half-life of carbon-11. 68Ga-pentixafor, which targets CXCR4 receptors that are overexpressed in aldosterone-producing adenomas but low or undetectable in normal adrenal tissue and nonfunctioning adenomas, was noninferior to adrenal vein sampling in 63 surgically treated patients in the guideline's cited study, and an independent meta-analysis reported 80% sensitivity and 91.5% specificity for lateralization with a 79% concordance rate to adrenal vein sampling across five studies, making it the more promising of the two candidates even though neither has displaced adrenal vein sampling as the guideline-endorsed standard.