# Primary aldosteronism

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## TL;DR

Primary aldosteronism is a hormonal condition in which one or both adrenal glands make too much of a hormone that raises blood pressure. It is a common but badly under-diagnosed cause of hypertension, usually flagged by a blood test, and curable with surgery when only one gland is overactive.

## Summary

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.

## Fields

- Kind: Indication
- Last checked: 2026-09-23
- Also known as: PA; primary hyperaldosteronism; hyperaldosteronism
- Tags: endocrine; hypertension; screening
- Group: endocrine
- Burden: The 2025 Endocrine Society guideline estimates primary aldosteronism prevalence at 5% to 14% of hypertensive people in primary care and up to 30% in referral centres, rising to 11.3% to 29.1% in resistant hypertension and 28.1% in hypertension with hypokalaemia. Screening is nonetheless rare: fewer than 1% of a Canadian cohort of one million hypertensive people had been screened, and only 2.1% of eligible people with resistant hypertension in a large US registry cohort were screened within two years of meeting criteria. A meta-analysis of 31 studies found increased odds of stroke, coronary artery disease, atrial fibrillation and heart failure compared with essential hypertension, and a separate meta-analysis of 46 studies found increased odds of albuminuria and proteinuria.
- Subtypes: Unilateral aldosterone-producing adenoma (lateralizing disease), the form treated by adrenalectomy; Bilateral adrenal hyperplasia (bilateral primary aldosteronism), treated medically rather than surgically; Primary aldosteronism with mild autonomous cortisol co-secretion, found on 1-mg dexamethasone suppression testing in roughly 5% to 27% of cases depending on the series
- Biomarkers: Aldosterone to renin ratio (ARR), the screening test; a ratio above 20 with suppressed renin and aldosterone above threshold indicates a positive screen and triggers confirmatory or subtyping workup; Serum potassium, measured alongside aldosterone and renin to avoid a false negative, since low potassium can artificially lower aldosterone; Aldosterone suppression testing (salt loading, fludrocortisone or saline infusion), used selectively when screening suggests an intermediate probability of lateralizing disease; 1-mg overnight dexamethasone suppression test, recommended in all patients with an adrenal adenoma to detect mild autonomous cortisol co-secretion; Adrenal vein sampling selectivity index (adrenal vein to IVC cortisol ratio) and lateralization index (cortisol-corrected aldosterone ratio, high side to low side), used to confirm successful catheterisation and determine unilateral versus bilateral disease; Renin during mineralocorticoid receptor antagonist therapy, monitored to titrate dose, since persistently suppressed renin on treatment is associated with higher cardiovascular event rates

## Standard of care

- All individuals with hypertension: Screening for primary aldosteronism is suggested for everyone with hypertension, using the aldosterone to renin ratio alongside serum potassium for accurate interpretation.
- Positive screen, intermediate probability of lateralizing disease: Aldosterone-suppression testing is suggested when screening results give an intermediate probability of lateralizing disease and the patient wants to pursue surgical eligibility.
- Confirmed primary aldosteronism considering surgery: Adrenal lateralization with CT scanning and adrenal vein sampling is suggested before deciding between medical and surgical treatment, except in young patients under 35 with marked disease and a clear unilateral adenoma over 1 cm on CT, where adrenalectomy without prior adrenal vein sampling can be considered.
- Lateralizing disease, surgical candidate who wants surgery: Unilateral adrenalectomy should be considered preferable over nonspecific antihypertensive therapy.
- Bilateral disease, or lateralizing disease in a non-surgical candidate: Medical treatment with a mineralocorticoid receptor antagonist should be considered preferable over nonspecific antihypertensive therapy, with spironolactone preferred over other agents for cost and availability and started at 12.5 to 25 mg daily, titrated to blood pressure, potassium and renin.
- All patients with primary aldosteronism and an adrenal adenoma: A 1-mg overnight dexamethasone suppression test is suggested to screen for mild autonomous cortisol co-secretion, which can complicate interpretation of adrenal vein sampling and prompts further Cushing syndrome evaluation if positive.

## State of the art

- The 2025 Endocrine Society Clinical Practice Guideline, published in the Journal of Clinical Endocrinology and Metabolism and presented at ENDO 2025, replaces the 2016 guideline and pushes for substantially more widespread screening than currently occurs in practice.
- The European Society of Cardiology's 2024 hypertension guidelines went further, advancing to a Class IIa, Level B recommendation for systematic aldosterone to renin ratio screening in all adults with confirmed hypertension.
- Positron emission tomography with aldosterone synthase-specific tracers is discussed only as a research consideration rather than a recommendation, aimed at eventually reducing reliance on adrenal vein sampling and the specialised interventional radiology it requires.
- Of the tracers studied, 68Ga-pentixafor targeting CXCR4 has shown more consistent concordance with adrenal vein sampling than dexamethasone-suppressed 11C-metomidate, though neither has been adopted as a guideline-endorsed subtyping tool.

## Open problems

- Screening is guideline-endorsed for almost all hypertensive patients but is essentially never performed in practice, with fewer than 1% screened in a Canadian cohort of one million hypertensive individuals.
- Even in resistant hypertension, the highest-risk group, only about 1 in 50 eligible patients receive guideline-recommended screening within two years of becoming eligible.
- Adrenal CT alone misclassifies a substantial share of patients relative to adrenal vein sampling, with one evidence summary reporting CT or MRI misdiagnosed the cause of disease in 37.8% of individuals, and CT-based management alone is associated with lower odds of biochemical cure after surgery.
- Adrenal vein sampling itself is technically demanding and provision is uneven, with success rates depending heavily on operator experience and one international study finding it was completed in only 77% of confirmed cases on average across centres, ranging from 19% to 100%.
- Functional imaging that could reduce reliance on adrenal vein sampling remains investigational, with mixed evidence between candidate tracers and no PET or scintigraphy option currently endorsed by guideline recommendation for routine subtyping.

## Sources

- 2025 Endocrine Society Primary Aldosteronism Clinical Practice Guideline, JCEM: https://academic.oup.com/jcem/article/110/9/2453/8196671
- Endocrine Society guideline summary page: https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2
- Endocrine Society news release calling for increased screening: https://www.endocrine.org/news-and-advocacy/news-room/2025/endocrine-society-guideline-calls-for-increased-screening-for-common-cause-of-high-blood-pressure
- Screening rates for primary aldosteronism in resistant hypertension, a cohort study: https://med.stanford.edu/content/dam/sm/urology/JJimages/publications/Screening-rates-for-primary-aldosteronism-in-resistant-hypertension-A-cohort-study.pdf
- CCJM interpretive review of primary aldosteronism management: https://www.ccjm.org/content/93/9/515
- Universal screening for primary aldosteronism in hypertensive patients: https://pmc.ncbi.nlm.nih.gov/articles/PMC12459304/

## Connected records

- targets: [CXCR4](https://nuclide.cc/targets/cxcr4/)
- drugs: [Gallium-68 pentixafor](https://nuclide.cc/drugs/ga-68-pentixafor/)
- opportunities: [CXCR4 imaging instead of adrenal vein sampling](https://nuclide.cc/opportunities/opp-cxcr4-primary-aldosteronism/)
- isotopes: [Carbon-11](https://nuclide.cc/isotopes/c-11/), [Gallium-68](https://nuclide.cc/isotopes/ga-68/)
- technologies: [PET/CT](https://nuclide.cc/technologies/pet-ct/)

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