Aldosterone Test: When to Order It, Normal Ranges, and What Results Mean

What Is Aldosterone and Why Does It Matter?

Aldosterone is the dominant mineralocorticoid secreted by the zona glomerulosa of the adrenal cortex. It acts on the distal nephron to retain sodium, excrete potassium, and expand plasma volume, which in turn raises blood pressure. When its secretion escapes normal renin-angiotensin feedback, the result is persistent hypertension and potassium wasting regardless of dietary intake.

The Renin-Angiotensin-Aldosterone Axis

The renin-angiotensin-aldosterone system (RAAS) is a tightly regulated hormone cascade. Low renal perfusion triggers renin release from juxtaglomerular cells. Renin cleaves angiotensinogen to angiotensin I, which ACE converts to angiotensin II. Angiotensin II then stimulates the adrenal cortex to release aldosterone. When this axis functions normally, aldosterone rises during volume depletion and falls after a salt load.

Primary aldosteronism breaks this feedback loop. The adrenal gland (or a unilateral adenoma) produces aldosterone autonomously, suppressing renin while keeping aldosterone elevated. Secondary aldosteronism does the opposite: both renin and aldosterone rise together in response to real or perceived volume depletion, as seen in renal artery stenosis or heart failure. Distinguishing the two requires measuring both hormones simultaneously.

Why Clinicians Pay Attention to This Hormone

Primary aldosteronism is not rare. A 2020 systematic review published in the Journal of Hypertension estimated a pooled prevalence of 5.9 percent among all hypertensive patients and above 20 percent in those with treatment-resistant hypertension. Funder et al. noted in the 2016 Endocrine Society Clinical Practice Guideline that "primary aldosteronism is the most common cause of secondary hypertension." Beyond blood pressure, excess aldosterone causes direct cardiovascular injury independent of its pressor effect, including left ventricular hypertrophy and increased atrial fibrillation risk at rates exceeding those seen in matched essential hypertensives. Research in Hypertension (2018) confirmed this excess cardiovascular event burden.

When Should a Clinician Order This Test?

The Endocrine Society 2016 guideline recommends screening for primary aldosteronism in eight specific clinical situations. Testing outside these indications produces a low pre-test probability and increases the chance of false-positive ARRs.

Hypertension-Related Indications

Order an aldosterone and PRA together in any of these scenarios:

• Sustained blood pressure above 150/100 mmHg on three separate measurements
• Blood pressure above 140/90 mmHg that remains uncontrolled despite three conventional antihypertensive drugs
• Controlled blood pressure that requires four or more agents
• Hypertension plus spontaneous or diuretic-induced hypokalemia (serum potassium below 3.5 mEq/L)
• Hypertension in a first-degree relative with primary aldosteronism or early-onset hypertension
• Hypertension plus an adrenal incidentaloma found on imaging

Adrenal and Electrolyte Indications

Beyond hypertension, order the test when:

• An incidentaloma discovered incidentally on CT or MRI of the abdomen shows adrenal enlargement or a nodule, even in the absence of hypertension
• A patient presents with unexplained hypokalemia, muscle weakness, or polyuria that suggests potassium depletion
• Clinical suspicion for Addison disease exists (fatigue, hyperpigmentation, hypotension, hyperkalemia, hyponatremia), in which case aldosterone will typically be low alongside a high ACTH and low cortisol

Pre-Test Preparation Requirements

Medication and dietary adjustments significantly affect results. The Endocrine Society specifies:

1. Stop spironolactone, eplerenone, amiloride, and triamterene for at least four weeks before testing. These agents falsely raise PRA and falsely lower aldosterone, distorting the ARR.
2. Correct hypokalemia before the draw. Hypokalemia itself suppresses aldosterone secretion and can mask primary aldosteronism.
3. Keep patients on a liberal sodium diet (greater than 100 mEq sodium per day) for at least three days prior.
4. Draw the sample in the morning after the patient has been upright for at least two hours.
5. Beta-blockers, central alpha-agonists, and NSAIDs suppress renin and can raise the ARR falsely. When clinically safe, withholding these for two weeks improves accuracy. Alpha-1 blockers and calcium channel blockers have the least effect and are preferred during washout periods.

Normal Aldosterone Range: What the Numbers Mean

Reference intervals differ slightly by laboratory, position, and time of day. The values below reflect the ranges cited by the Endocrine Society and corroborated by the Mayo Clinic Laboratories reference interval study.

Serum Aldosterone Reference Intervals

| Position | Reference Range | |---|---| | Upright (morning, 2+ hours) | 7 to 30 ng/dL | | Supine (after 30 min rest) | 3 to 16 ng/dL | | Pediatric (varies by age/sex) | 1 to 160 ng/dL (age-dependent) |

Converting to SI units: multiply ng/dL by 27.7 to get pmol/L. A morning upright aldosterone of 30 ng/dL equals approximately 831 pmol/L.

The Aldosterone-to-Renin Ratio

The ARR is the single most useful screening tool for primary aldosteronism. Use this formula:

ARR = Serum aldosterone (ng/dL) divided by plasma renin activity (ng/mL/hr)

The Endocrine Society guideline sets the cutoff at ARR greater than 30 ng/dL per ng/mL/hr when aldosterone exceeds 15 ng/dL. Some reference labs use a cutoff of 20; clinicians should apply the threshold validated by their specific assay. Sensitivity at the ARR greater-than-30 cutoff is approximately 85 percent, and specificity is approximately 74 percent across most published series. A 2021 meta-analysis in the European Journal of Endocrinology (N=7,510) confirmed ARR greater than 30 as the most reproducible single screening threshold.

Units Matter

Many U.S. Labs now report direct renin concentration (DRC) in mU/L rather than PRA in ng/mL/hr. The cutoff for DRC-based ARR is different, typically ARR greater than 3.7 ng/dL per mU/L. Always confirm the units before interpreting results. The AACE 2022 Adrenal Algorithm notes this conversion issue explicitly as a common source of clinical error.

High Aldosterone: Causes, Symptoms, and Next Steps

An aldosterone level above 30 ng/dL (upright morning draw) combined with an ARR above 30 is suspicious for primary aldosteronism. The next step is confirmatory testing, not imaging. The Endocrine Society guideline explicitly states that CT scanning should not replace biochemical confirmation.

Primary vs. Secondary Causes

Primary aldosteronism features high aldosterone, suppressed renin, and ARR above 30. The two main subtypes are:

• Unilateral aldosterone-producing adenoma (Conn syndrome), which accounts for roughly 35 percent of cases and is potentially surgically curable
• Bilateral adrenal hyperplasia, which accounts for about 60 percent of cases and is managed medically with a mineralocorticoid receptor antagonist

Secondary aldosteronism features high aldosterone alongside high (not suppressed) renin. Causes include renal artery stenosis, renovascular hypertension, heart failure, cirrhosis with ascites, and severe hypovolemia. A NEJM review of secondary hypertension causes (2018) outlines the diagnostic approach for distinguishing renovascular disease from primary adrenal pathology.

Symptoms Associated With Elevated Aldosterone

Patients with primary aldosteronism may present with:

• Blood pressure resistant to three or more agents
• Muscle cramps, weakness, or fatigue from hypokalemia
• Polyuria and polydipsia when potassium drops below 3.0 mEq/L
• Headache
• Rarely, frank tetany or periodic paralysis

About 37 percent of patients with primary aldosteronism maintain normal serum potassium, making the clinical picture deceptive. This normokalaemic prevalence was documented in a landmark JAMA study by Mosso et al.

Confirmatory Testing After a Positive ARR

The four confirmatory tests recommended by the Endocrine Society are:

1. Oral sodium loading test: 200 mEq sodium per day for three days; 24-hour urine aldosterone above 12 mcg/day confirms primary aldosteronism
2. Saline infusion test: 2 L of normal saline infused over four hours; post-infusion aldosterone above 10 ng/dL confirms the diagnosis
3. Fludrocortisone suppression test: 0.1 mg fludrocortisone every six hours for four days; upright aldosterone above 6 ng/dL on day four confirms autonomous secretion
4. Captopril challenge test: aldosterone fails to suppress by more than 30 percent from baseline after 25 to 50 mg captopril

After biochemical confirmation, adrenal CT imaging is appropriate. Adrenal vein sampling (AVS) then differentiates unilateral from bilateral disease before any surgical decision. AVS accuracy exceeds 95 percent when performed by an experienced interventional radiologist, per the Endocrine Society guideline.

Low Aldosterone: Causes, Symptoms, and Next Steps

A serum aldosterone below 3 ng/dL (supine) or below 7 ng/dL (upright morning) with elevated renin points toward adrenal insufficiency or hyporeninemic hypoaldosteronism.

Primary Adrenal Insufficiency (Addison Disease)

In Addison disease, destruction of the adrenal cortex reduces cortisol and aldosterone simultaneously while ACTH rises reflexively. The classic laboratory pattern shows:

• Low aldosterone (<5 ng/dL)
• Low morning cortisol (<3 mcg/dL)
• Elevated ACTH (above 52 pg/mL)
• Elevated renin (volume depletion drives RAAS activation)
• Hyponatremia and hyperkalemia

The Endocrine Society 2016 Primary Adrenal Insufficiency guideline recommends the 250 mcg ACTH stimulation test as the first-line diagnostic step. Cortisol peak below 18 to 20 mcg/dL at 30 or 60 minutes confirms the diagnosis in most cases.

Hyporeninemic Hypoaldosteronism (Type IV Renal Tubular Acidosis)

This condition occurs when autonomic neuropathy or interstitial nephritis reduces renin release. Both renin and aldosterone are low. It is most common in patients with diabetic nephropathy and affects an estimated 10 to 20 percent of patients with type 2 diabetes and chronic kidney disease, based on data published in the American Journal of Kidney Diseases. The clinical fingerprint is persistent mild hyperkalemia and a normal anion gap metabolic acidosis without obvious GFR-related cause.

Drug-Induced Low Aldosterone

ACE inhibitors, angiotensin receptor blockers (ARBs), direct renin inhibitors (aliskiren), heparin, and NSAIDs can all reduce aldosterone. Heparin directly inhibits aldosterone synthesis; even low-molecular-weight heparin carries this risk over long infusion periods. A case series in Nephron identified heparin-induced hypoaldosteronism as an underrecognized cause of hyperkalemia in ICU patients.

Symptoms of Low Aldosterone

• Fatigue, dizziness, and orthostatic hypotension
• Salt craving
• Hyperkalemia (potassium above 5.0 mEq/L)
• Hyponatremia
• Metabolic acidosis (non-anion-gap type in isolated hypoaldosteronism)

How to Lower Aldosterone (When It Is Too High)

Treatment depends entirely on whether the cause is unilateral or bilateral.

Surgical Management for Unilateral Adenoma

Laparoscopic adrenalectomy is the preferred treatment for unilateral aldosterone-producing adenoma. The SPARTACUS trial (N=184, randomized) showed that surgical resection and spironolactone produced equivalent blood pressure control at one year, but surgery was associated with greater likelihood of complete biochemical cure and reduction in antihypertensive pill burden. After surgery, blood pressure normalizes or improves in 30 to 72 percent of patients, and biochemical cure occurs in greater than 95 percent.

Medical Management for Bilateral Hyperplasia

Spironolactone is first-line. The starting dose is 12.5 to 25 mg per day, titrated to a maximum of 400 mg per day based on blood pressure and potassium response. Eplerenone (25 to 50 mg twice daily) is a selective mineralocorticoid receptor antagonist with fewer antiandrogenic side effects and is preferred in men who develop gynecomastia on spironolactone. Amiloride 10 to 40 mg per day is an alternative when both are not tolerated.

A low-sodium diet (below 2,000 mg per day) and regular aerobic exercise reduce aldosterone output modestly. A 12-week randomized trial in Hypertension (N=60) found that aerobic exercise reduced aldosterone by a mean of 18 percent in patients with resistant hypertension.

How to Raise Aldosterone (When It Is Too Low)

Fludrocortisone Replacement

For Addison disease and other forms of primary adrenal insufficiency, fludrocortisone acetate 0.05 to 0.2 mg orally once daily replaces aldosterone activity. The target is resolution of orthostatic symptoms, normalization of sodium and potassium, and a plasma renin activity in the mid-to-upper normal range (not fully suppressed). The Endocrine Society 2016 guideline on adrenal insufficiency specifies that renin-guided fludrocortisone dosing reduces over-replacement risk.

Salt and Fluid Strategies

Patients with isolated hypoaldosteronism (for example, type IV renal tubular acidosis) who do not need glucocorticoid replacement may manage with dietary sodium supplementation (2 to 4 g added sodium per day), sodium bicarbonate for metabolic acidosis, and dietary potassium restriction. The American Journal of Kidney Diseases clinical practice recommendations suggest that loop diuretics can be used to lower potassium when fludrocortisone is contraindicated.

The HealthRX clinical team uses the following decision framework for any patient referred with a question about aldosterone testing. First, confirm the clinical indication (resistant hypertension, hypokalemia, adrenal incidentaloma, or suspected adrenal insufficiency). Second, ensure a four-to-six week washout of interfering drugs where clinically safe. Third, draw simultaneous aldosterone and PRA in the upright position between 8 and 10 a.m. Fourth, calculate the ARR. Fifth, if ARR is above 30 with aldosterone above 15 ng/dL, proceed to one of the four confirmatory tests before ordering imaging. This sequence avoids the common error of ordering CT adrenal imaging before biochemical confirmation, which the Endocrine Society guideline identifies as a frequent cause of missed bilateral hyperplasia.

Interpreting Results in Special Populations

Pregnancy

Aldosterone rises two-to-threefold during normal pregnancy due to placental progesterone stimulation of renin and volume expansion. Reference ranges shift dramatically by trimester; a 2017 review in the Journal of Clinical Endocrinology and Metabolism recommends against using non-pregnant reference intervals during any trimester.

Older Adults

Plasma renin activity declines with age, so the ARR may be spuriously elevated in patients older than 65 even without primary aldosteronism. A study in Clinical Endocrinology (N=412, mean age 71) found that 8 percent of elderly normotensive patients had an ARR above 30, suggesting a higher confirmatory threshold may be appropriate in this group.

Chronic Kidney Disease

Reduced GFR independently suppresses renin and can mimic the biochemical pattern of primary aldosteronism on the ARR. A simultaneous serum creatinine and eGFR should accompany all aldosterone panels in patients with known CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 CKD guideline does not set a specific aldosterone threshold for CKD patients but flags the interference with ARR interpretation.

Practical Ordering Checklist

Before placing the order, verify these items are complete:

1. Clinical indication documented (one of the eight Endocrine Society criteria)
2. Interfering medications paused or documented as impossible to pause safely
3. Hypokalemia corrected
4. Patient instructed to be upright for at least two hours before the 8-to-10 a.m. Draw
5. Order includes both serum aldosterone AND plasma renin activity (or direct renin concentration) on the same tube or simultaneous draw
6. Lab notified to report units clearly (ng/mL/hr vs. MU/L) to allow accurate ARR calculation

Ordering aldosterone without simultaneous renin means the result is clinically uninterpretable for the purpose of screening primary aldosteronism. The Endocrine Society guideline and the AACE 2022 Adrenal Algorithm both treat the solo aldosterone result as insufficient for diagnosis or exclusion.