Primary Aldosteronism: Why Hypertension Screening Expanded

Primary aldosteronism occurs when aldosterone production is inappropriately high relative to the body's renin signal. The result can be sodium retention, suppression of renin, potassium loss in some people, and sustained blood-pressure elevation. For years, testing focused mainly on resistant hypertension, low potassium, or an adrenal mass. That approach misses many cases.

The Endocrine Society's 2025 guideline suggests screening all people with hypertension rather than only selected high-risk groups, while acknowledging feasibility, false positives, and resource constraints. The shift reflects evidence that primary aldosteronism exists across the spectrum of hypertension and that most affected people do not present with the classic textbook combination of severe hypertension and spontaneous hypokalemia.

Screening is only the first step. Aldosterone, renin, and potassium are the numbers, but what they mean depends on the medicines you take, your sodium balance, whether you were sitting or standing, the time of day, the assay the laboratory runs, and how likely the condition was before anyone tested. A positive ratio is not a stand-alone diagnosis.

Aldosterone and renin as a feedback system#

Renin is released by the kidney when the body senses reduced perfusion, reduced sodium delivery, or sympathetic stimulation, and it helps generate angiotensin II, which stimulates aldosterone production in the adrenal cortex. Aldosterone promotes sodium retention and potassium excretion in the kidney.

In ordinary physiology, the system turns down when volume and sodium retention rise. In primary aldosteronism, aldosterone production becomes relatively autonomous. Renin is often suppressed while aldosterone remains inappropriate for that low-renin state.

The condition is not defined by a single universally high aldosterone concentration. A value that looks modest in isolation can be inappropriate when renin is profoundly suppressed, which is why the two hormones are measured at the same time and read against each other.

Why the condition is missed#

The classic teaching emphasized hypertension plus hypokalemia, though many people with primary aldosteronism have potassium within the laboratory range, especially earlier in the disease or while diet, kidney handling, and medicines compensate. Waiting for low potassium selects a more obvious subset.

Diagnosis is also a multistep process. Test preparation can be complex, assays differ, and referral pathways may be limited. Clinicians may assume that finding a cause will not change treatment, especially when blood pressure already responds to ordinary medicines.

Yet aldosterone excess appears to carry cardiovascular and kidney risk beyond the measured blood pressure alone. Targeted treatment can address the mineralocorticoid pathway, while selected unilateral disease may have a surgical option. Those consequences strengthen the case for detection.

How common is it?#

Prevalence varies with population, test definitions, confirmation methods, and hypertension severity. Research using systematic testing suggests a continuum of renin-independent aldosterone production, including people without resistant hypertension. Estimates are higher in resistant hypertension than in general hypertensive populations.

The 2025 ACC/AHA blood-pressure guideline summarizes prevalence around 5 to 10 percent among people with hypertension and around 20 percent in resistant hypertension, while emphasizing low screening rates among eligible patients. These are population estimates. They are not the probability that you, in particular, have it.

Broad screening changes the tested population. When prevalence is lower than in a specialty referral group, false-positive screens become more consequential. A guideline's suggestion must therefore be implemented with assay-aware pathways and capacity for interpretation, not simply a ratio flag in an electronic record.

What the screening test measures#

Screening generally includes plasma or serum aldosterone, renin measured as activity or direct concentration, and potassium. The aldosterone-to-renin ratio, or ARR, highlights aldosterone that is high relative to suppressed renin.

There is no universal ARR cutoff that transfers unchanged across laboratories. Renin activity and direct renin concentration use different units and assay behavior. Aldosterone assays differ too. A very low renin value can make the ratio large even when aldosterone is low, so clinicians should inspect both components and the laboratory's validated threshold.

Potassium matters because low potassium can suppress aldosterone secretion and produce a misleadingly lower value. It also signals potential severity and affects safety planning. Sodium intake, posture, time of collection, kidney function, age, and acute illness can alter the system.

Medicines can move the numerator and denominator#

Many antihypertensive drugs affect renin, aldosterone, or both. Beta blockers can suppress renin and create a higher ratio. Diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers can raise renin and potentially obscure a low-renin pattern. Mineralocorticoid-receptor antagonists directly affect the pathway and can complicate interpretation.

That does not mean you should stop your medicines on your own before a test. Sudden changes can destabilize blood pressure, potassium, heart failure, or another condition. The 2025 guideline describes strategies that balance ideal testing conditions with safety and feasibility, including interpretation on existing therapy in some situations and planned adjustment in others.

The report should document current medicines, timing, potassium, sodium context, collection conditions, and assay. If a result conflicts with clinical probability, repeating the test under a clinician-directed plan may tell you more than treating the first result as definitive.

A screen is not the final diagnosis#

A convincing biochemical pattern can have different next steps depending on aldosterone level, renin suppression, potassium, and clinical probability. Confirmatory suppression tests ask whether aldosterone can be appropriately reduced under a standardized condition. Options include saline, oral sodium, captopril, and fludrocortisone protocols, each with limitations and safety considerations.

Not every person needs every confirmatory test. In a high-probability presentation with marked renin suppression, clearly elevated aldosterone, and hypokalemia, further suppression testing may add little. In a borderline broad-screening result, confirmation can protect against labeling and treatment based on a false positive. Selection should account for kidney function, heart failure, blood pressure severity, local expertise, and assay interpretation. These tests are clinician-supervised procedures, not home diagnostic experiments.

Determine subtype only when it changes the plan#

After biochemical diagnosis, the next question is whether aldosterone excess arises mainly from one adrenal gland or from both. Unilateral production may come from an aldosterone-producing adenoma or unilateral hyperplasia. Bilateral adrenal hyperplasia is commonly treated medically.

Adrenal computed tomography helps identify anatomy and exclude a large or suspicious mass. It cannot reliably determine which gland is producing aldosterone. Nonfunctioning adrenal nodules become common with age, while a small functioning lesion may be missed.

Adrenal venous sampling measures hormone patterns from each adrenal vein and is often used to determine lateralization when a person is considering surgery. It is technically demanding and requires experienced teams. Imaging and sampling answer related but different questions: structure versus functional secretion. So if surgery is not something you want, or is not medically appropriate for you, extensive lateralization testing may not change management. The intensity of the testing should follow the decision it is meant to support.

Treatment follows physiology and subtype#

For confirmed unilateral disease in an appropriate surgical candidate, adrenalectomy can reduce aldosterone excess and often improves blood pressure and potassium. It does not guarantee that every antihypertensive medicine will become unnecessary, because vascular changes, age, kidney disease, and coexisting essential hypertension may remain.

For bilateral disease, uncertain lateralization, or a nonsurgical pathway, mineralocorticoid-receptor antagonists block aldosterone's effect. Treatment requires monitoring of potassium, kidney function, blood pressure, symptoms, and adverse effects; the guideline also emphasizes renin as one possible marker of adequate pathway blockade in selected contexts, rather than focusing on blood pressure alone. Other medicines and lifestyle measures may still be needed for overall cardiovascular risk. Targeted therapy addresses an important mechanism, not every cause of hypertension.

Three patterns that illustrate interpretation#

Resistant hypertension with low potassium#

This pattern creates high pretest probability, but diuretic use and other causes of potassium loss still need consideration. Suppressed renin with clearly inappropriate aldosterone strengthens the case and can shorten the confirmation pathway in the right context.

Mild hypertension with normal potassium#

Normal potassium does not exclude the condition. Broad screening is intended to find less obvious cases, but the lower pretest probability makes assay quality, medication effects, and confirmation especially important.

High ratio driven only by extremely low renin#

A large ratio can look dramatic when the denominator approaches the assay floor. If aldosterone itself is low, medication effects, sodium state, age, and assay limits need review. The components should never be replaced by the ratio alone.

What a reliable screening program requires#

A health system adopting broad screening needs standardized ordering, collection instructions, assay-specific interpretation, medication guidance, repeat-test pathways, access to confirmation, and referral criteria, and it also needs capacity for adrenal imaging, experienced sampling where indicated, surgery, and long-term medical monitoring.

Quality should be judged across the pathway: who is offered testing, how often samples are interpretable, false-positive burden, completion of follow-up, time to targeted treatment, outcomes, adverse effects, and equity. Counting ARR orders alone would reward screening without ensuring benefit.