# Primary Aldosteronism Screening Interpretation

Interpret primary aldosteronism screening by assessing aldosterone and renin together, accounting for potassium status and medications, then selecting confirmatory testing or direct subtype evaluation when the biochemical phenotype is unequivocal.

**Clinical question:** How should physicians interpret aldosterone and renin results when screening hypertensive patients for primary aldosteronism?

Updated: 2026-09-15T18:36:31.602853+00:00

## What matters in practice
- Screen hypertensive patients by measuring aldosterone and renin simultaneously and calculating the aldosterone-renin ratio; the 2025 Endocrine Society guideline suggests screening all patients with hypertension. [8]
- An ARR greater than 30 with plasma aldosterone greater than 10 ng/dL is a commonly used positive screening pattern, but assay-specific cutoffs and medication effects require interpretation of the individual aldosterone and renin values rather than the ratio alone. [18][19][20]
- Correct hypokalemia and avoid sodium restriction before testing because potassium, sodium balance, and antihypertensive drugs materially alter renin, aldosterone, and the ARR. [20][24]
- Spontaneous hypokalemia, suppressed renin, and plasma aldosterone greater than 20 ng/dL can establish primary aldosteronism without confirmatory suppression testing. [19]
- After biochemical confirmation, obtain adrenal CT to exclude adrenal malignancy and use adrenal venous sampling when lateralization will determine whether adrenalectomy is appropriate. [20][23][24]

## Who should undergo aldosterone-renin screening

Order paired aldosterone and renin testing whenever the result could redirect hypertension treatment toward mineralocorticoid blockade or adrenalectomy.

The current Endocrine Society guideline suggests screening all individuals with hypertension by measuring aldosterone and renin and determining the aldosterone-to-renin ratio (ARR). [8] In settings using risk-enriched testing, prioritize resistant hypertension, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, early stroke before age 40 years in the family, early-onset hypertension, or hypertension in a first-degree relative of a patient with primary aldosteronism. [16][21]

Do not use normal potassium to exclude primary aldosteronism. Expansion of ARR-based testing has identified many normokalemic patients, and primary aldosteronism has been reported in approximately 6% of primary care hypertension and is more frequent in resistant hypertension. [16][21] The practical threshold for testing should therefore be low when renin is suppressed, hypertension is difficult to control, or a potentially curable adrenal cause would alter management.
- Screen patients with resistant hypertension, including blood pressure above 140/90 mm Hg despite three drugs that include a diuretic. [17]
- Screen patients with spontaneous or diuretic-associated hypokalemia, even if blood pressure is controlled. [16][21]
- Screen patients with hypertension plus an adrenal incidentaloma, atrial fibrillation, obstructive sleep apnea, or relevant family history. [16][21]

*Clinical settings that should lower the threshold for paired aldosterone-renin testing. [8][16][21]*

| Clinical context | Why screening changes management |
| --- | --- |
| Resistant hypertension | Primary aldosteronism is enriched in this population; a positive evaluation identifies candidates for targeted mineralocorticoid receptor antagonism or subtype-directed treatment. [17][21] |
| Hypokalemia with hypertension | Hypokalemia may reflect clinically important mineralocorticoid excess and should be corrected before interpreting the ARR. [16][24] |
| Hypertension plus adrenal nodule | A positive biochemical screen determines whether the lesion requires primary aldosteronism confirmation and subtype evaluation rather than imaging-based attribution alone. [21][23] |
| Hypertension with atrial fibrillation, obstructive sleep apnea, or family history of early hypertension or stroke | These associated phenotypes identify patients in whom case detection is recommended. [16][21] |

## How to obtain an interpretable screening sample

A technically valid sample reduces false reassurance from stimulated renin or suppressed aldosterone.

Measure plasma aldosterone concentration and either plasma renin activity or direct renin concentration at the same draw, then calculate the ARR using the laboratory's assay-specific units and reference framework. [8][20] For higher sensitivity, collect blood in the morning after the patient has been out of bed for at least 2 hours and seated for 5 to 15 minutes. [24]

Before testing, correct hypokalemia and avoid dietary sodium restriction; potassium depletion can reduce aldosterone secretion, while sodium and potassium status alter both components of the ARR. [20][24] A low potassium value accompanying a low or modest aldosterone concentration should trigger potassium repletion and repeat paired testing rather than dismissal of the diagnosis.

Medication withdrawal is a tradeoff between analytic purity and blood pressure safety. Mineralocorticoid receptor antagonists and other diuretics are ideally withdrawn for at least 4 weeks before testing; one review recommends 4 to 6 weeks for spironolactone or eplerenone because these agents increase renin and can obscure renin suppression. [23][24] If withdrawal is unsafe, suppressed renin with high aldosterone remains strongly suggestive of primary aldosteronism. [24]
- Document the renin method—plasma renin activity versus direct renin concentration—before applying an ARR cutoff. [20]
- If feasible, discontinue beta-blockers because renin suppression can produce a false-positive ARR; withdrawal often does not critically compromise blood pressure control. [20]
- ACE inhibitors, angiotensin receptor blockers, and diuretics tend to increase renin and may lower the ARR, creating potential false-negative screening results. [23]
- When a temporary regimen is needed during medication adjustment, calcium channel blockers and alpha-adrenergic blockers are used in standardized testing strategies; prazosin may be started at 0.5 to 1 mg two or three times daily, doxazosin at 1 to 2 mg daily, or terazosin at 1 to 2 mg daily, with monitoring for postural hypotension. [7][10]

### Testing while the patient takes a mineralocorticoid receptor antagonist

Do not automatically abandon screening because a patient is receiving spironolactone or eplerenone. If renin remains suppressed despite an MRA, proceed with case detection; persistent suppression indicates that mineralocorticoid receptor blockade is incomplete or that autonomous aldosterone physiology remains demonstrable. [14] Conversely, an unsuppressed renin concentration or activity while receiving an MRA may require MRA discontinuation for 6 weeks before retesting if formal diagnostic clarification is needed. [14]

*Common medication effects that change ARR interpretation. [20][23][24]*

| Medication class | Expected screening distortion | Interpretive response |
| --- | --- | --- |
| Beta-blocker | Suppresses renin and may cause a false-positive ARR. [20][23] | Discontinue when clinically feasible and repeat paired aldosterone-renin testing. [20] |
| ACE inhibitor or ARB | Raises renin and may suppress aldosterone, tending toward a falsely low ARR. [23] | A high ARR despite therapy remains concerning; a non-diagnostic result may require repeat testing under a modified regimen. [23] |
| Non-MRA diuretic | Raises renin and can lower the ARR. [23][24] | Withdraw for at least 4 weeks when clinically safe before repeat testing. [24] |
| Spironolactone or eplerenone | Raises renin and can obscure renin suppression. [14][23] | If renin is suppressed, testing can proceed; if renin is not suppressed and definitive testing is required, discontinue and retest after an adequate washout. [14] |

## What constitutes a positive primary aldosteronism screen

Interpret the ARR as a paired hormone pattern, not as an isolated numeric diagnosis.

A positive screen requires renin suppression with aldosterone that is inappropriately elevated for the renin state. A commonly applied screening pattern is ARR greater than 30 when aldosterone is greater than 10 ng/dL, using aldosterone in ng/dL and plasma renin activity in ng/mL/hour. [18][19][21] This is a screening threshold, not a universal diagnostic cutoff: ARR thresholds vary by assay and unit system, and no single cutoff has uniform sensitivity or specificity. [5][20]

A high ARR driven only by very low renin is less persuasive when aldosterone is not clearly elevated, particularly during beta-blocker treatment, sodium excess, or uncorrected testing conditions. [20][23] Repeat a borderline or discordant result after correcting potassium, ensuring unrestricted salt intake, and modifying interfering antihypertensive therapy when feasible. [20][24]

A low or non-elevated ARR does not reliably exclude primary aldosteronism when renin has been pharmacologically stimulated by ACE inhibitors, ARBs, or diuretics. [23] In a patient with resistant hypertension or hypokalemia, repeat under more interpretable conditions or proceed to an alternative diagnostic strategy based on the total phenotype; ARR reproducibility and sensitivity are limited under some testing conditions. [10][18]
- Positive pattern: suppressed renin plus ARR greater than 30 and aldosterone greater than 10 ng/dL using the cited conventional units. [18][19][21]
- High-confidence pattern: spontaneous hypokalemia, suppressed renin, and aldosterone greater than 20 ng/dL; confirmatory suppression testing can be omitted. [19]
- Discordant pattern: low renin with low aldosterone, or borderline ARR obtained during potassium depletion or major medication interference; correct conditions and repeat rather than label primary aldosteronism. [20][23][24]

### Why an elevated ARR is not sufficient by itself

The ARR is vulnerable to assay variation, medication effects, and biologic variability. Prospective testing in patients with persistent hypertension found limited sensitivity and poor reproducibility at a recommended ARR cutoff, supporting repeat or dynamic testing when clinical suspicion remains high despite a non-diagnostic screening result. [10] Confirmatory testing should therefore be selected by local expertise, patient safety, and whether the biochemical phenotype is already unequivocal.

*Actionable interpretation of paired aldosterone-renin screening results. [18][19][20][23][24]*

| Biochemical pattern | Most likely interpretation | Next action |
| --- | --- | --- |
| ARR >30 with aldosterone >10 ng/dL and suppressed renin | Positive case-detection result compatible with renin-independent aldosterone excess. [18][19][21] | Perform confirmatory suppression testing unless the unequivocal exception applies. [19] |
| Spontaneous hypokalemia, suppressed renin, aldosterone >20 ng/dL | Primary aldosteronism can be diagnosed without confirmatory testing. [19] | Proceed to adrenal CT and determine candidacy for subtype evaluation and treatment. [20][23][24] |
| Elevated ARR during beta-blocker treatment with modest aldosterone elevation | Possible false-positive ratio due to drug-induced renin suppression. [20][23] | Stop beta-blocker when safe or repeat after regimen adjustment; interpret aldosterone and renin separately. [20] |
| Low or non-diagnostic ARR during ACE inhibitor, ARB, or diuretic therapy | Possible false-negative ratio from renin stimulation. [23] | Repeat after appropriate drug adjustment when clinical suspicion remains high. [23][24] |
| Low aldosterone with low renin | Does not establish primary aldosteronism; the ratio may be misleading when aldosterone is not inappropriately elevated. [20] | Review sodium status, medications, and alternative causes of low-renin hypertension; repeat under controlled conditions if indicated. [20][24] |

## When to confirm primary aldosteronism and when to subtype

Use suppression testing to establish autonomous secretion, then distinguish potentially unilateral from bilateral disease before surgery.

For most positive screening results, confirm autonomous aldosterone secretion with an oral sodium suppression test, saline infusion suppression test, fludrocortisone suppression test, or captopril challenge test. [18][19][21] These tests evaluate whether aldosterone appropriately suppresses after sodium loading, mineralocorticoid exposure, or renin-angiotensin system manipulation; persistent secretion supports primary aldosteronism. [18]

There is no universally accepted gold-standard confirmatory test or uniform post-test cutoff. [18][24] Select the test according to local protocol and patient safety rather than treating numerical thresholds from another assay platform as interchangeable. For example, one prospective intravenous salt-loading protocol considered post-test plasma aldosterone above 235 pmol/L diagnostic, but this threshold is protocol-specific. [10]

After confirmation—or after the unequivocal hypokalemic, suppressed-renin, aldosterone-greater-than-20-ng/dL presentation—obtain thin-cut adrenal CT. [19][23] CT identifies lesions requiring malignancy consideration but does not reliably establish aldosterone lateralization because nonfunctioning adrenal nodules are common and CT specificity for aldosterone-producing adenoma is poor. [23]

Offer adrenal venous sampling (AVS) to patients considering unilateral adrenalectomy when a lateralization result would change treatment. Bilateral AVS is the reference method for subtype classification and should be performed by an experienced radiologist. [20][24] Screen for autonomous cortisol secretion with a 1-mg overnight dexamethasone suppression test before AVS or adrenalectomy because concurrent cortisol excess can distort AVS interpretation and can contribute to postoperative adrenal insufficiency. [15]
- Skip confirmatory testing only for spontaneous hypokalemia, suppressed renin, and aldosterone greater than 20 ng/dL. [19]
- Use adrenal CT after biochemical diagnosis to assess adrenal anatomy and exclude adrenocortical carcinoma; do not use CT alone to determine surgical laterality. [23][24]
- Use AVS when the patient is a surgical candidate and distinction between unilateral and bilateral secretion will guide adrenalectomy versus medical therapy. [20][24]

*Post-screen diagnostic sequence for primary aldosteronism. [15][18][19][23][24]*

| Step | Indication | Decision produced |
| --- | --- | --- |
| Confirmatory suppression test | Positive ARR with no unequivocal biochemical phenotype. [18][19] | Establishes persistent renin-independent aldosterone secretion. [18] |
| Adrenal CT | Biochemically confirmed primary aldosteronism or confirmatory testing bypassed by the unequivocal phenotype. [19][23] | Assesses adrenal anatomy and excludes concerning mass lesions; does not establish lateralization. [23] |
| 1-mg overnight dexamethasone suppression test | Before AVS or adrenalectomy. [15] | Detects autonomous cortisol secretion that can affect AVS interpretation and perioperative risk. [15] |
| Adrenal venous sampling | Surgical candidate in whom lateralization will change treatment. [20][24] | Distinguishes unilateral from bilateral aldosterone secretion for treatment selection. [20][24] |

## How screening interpretation changes treatment

The purpose of case detection is to identify patients who need aldosterone-directed therapy rather than nonspecific escalation alone.

Unilateral primary aldosteronism is generally treated with laparoscopic adrenalectomy when the patient is an operative candidate and lateralization supports unilateral disease. [20][24] Patients with bilateral hyperplasia, nonlateralized AVS, operative contraindications, or preference against surgery should receive a mineralocorticoid receptor antagonist. [20][22][24]

Spironolactone is the preferred first-line mineralocorticoid receptor antagonist in current Endocrine Society guidance because of affordability and broad availability. [3] Eplerenone is a reasonable alternative when spironolactone causes breast tenderness, gynecomastia, sexual dysfunction, or menstrual irregularities; eplerenone is less potent and generally requires higher dosing. [22][23] One practical equivalence cited in hypertension guidance is spironolactone 25 mg daily approximately equivalent to eplerenone 25 mg twice daily. [22]

During mineralocorticoid receptor antagonist therapy, monitor blood pressure, serum potassium, and creatinine while titrating to the maximum tolerated dose needed for normokalemia and blood pressure control. [22] Amiloride 5 to 40 mg/day may be used as a substitute for or adjunct to an MRA when MRA intolerance prevents adequate treatment. [22]
- Lateralized unilateral disease: consider unilateral laparoscopic adrenalectomy. [20][24]
- Bilateral disease or no surgery: use spironolactone first line; consider eplerenone for spironolactone intolerance. [3][22][23]
- Monitor potassium and creatinine during MRA initiation and dose escalation because hyperkalemia can occur with spironolactone or eplerenone. [22][23]

*Treatment implications after subtype assessment. [3][20][22][23][24]*

| Clinical branch | Preferred approach | Monitoring or tradeoff |
| --- | --- | --- |
| Unilateral aldosterone secretion and surgical candidate | Unilateral laparoscopic adrenalectomy. [20][24] | Obtain appropriate subtype evaluation before surgery; assess for autonomous cortisol secretion before AVS or adrenalectomy. [15][24] |
| Bilateral adrenal hyperplasia or nonoperative patient | Spironolactone as first-line MRA. [3][22][24] | Monitor blood pressure, potassium, and creatinine; antiandrogenic and progestogenic adverse effects are dose dependent. [22] |
| Spironolactone intolerance | Eplerenone; 25 mg spironolactone daily is cited as approximately equivalent to eplerenone 25 mg twice daily. [22] | Greater receptor selectivity reduces sex-hormone adverse effects, but higher doses are generally needed and hyperkalemia remains possible. [22][23] |
| MRA intolerance or inadequate control | Amiloride 5 to 40 mg/day as substitute or adjunct. [22] | Continue electrolyte, creatinine, and blood pressure monitoring. [22] |

## Common questions

### Can primary aldosteronism be excluded in a normokalemic patient with a normal ARR?

No. Many patients with primary aldosteronism are normokalemic, and ACE inhibitors, ARBs, and diuretics can stimulate renin and lower the ARR. In a high-suspicion phenotype, correct testing conditions and repeat paired aldosterone-renin measurement rather than relying on a single non-diagnostic ratio. [16][23][24]

### Should an adrenal nodule on CT be assumed to be the source of aldosterone excess?

No. Adrenal CT is required after biochemical diagnosis to assess anatomy and exclude concerning lesions, but its specificity for identifying an aldosterone-producing adenoma is poor. Use AVS when surgical lateralization will determine management. [23][24]

## References
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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.