Aldosterone: What This Lab Test Actually Measures

What Aldosterone Is and Why It Matters

Aldosterone is a mineralocorticoid hormone synthesized in the zona glomerulosa, the outermost layer of the adrenal cortex. Its primary job is straightforward: signal the kidneys to hold onto sodium and water while excreting potassium. That exchange directly governs blood volume and, by extension, blood pressure 1.

The renin-angiotensin-aldosterone system (RAAS) is the feedback loop that controls aldosterone secretion. When blood pressure drops or sodium delivery to the distal nephron falls, the kidneys release renin. Renin converts angiotensinogen to angiotensin I, which angiotensin-converting enzyme (ACE) then converts to angiotensin II. Angiotensin II stimulates aldosterone release 2. Potassium concentration also directly stimulates the zona glomerulosa. Even a 0.1 mEq/L rise in serum potassium can measurably increase aldosterone output 3.

When this system malfunctions, the consequences are clinically significant. Excess aldosterone raises blood pressure, depletes potassium, and over years accelerates cardiac fibrosis, kidney damage, and vascular inflammation at rates that exceed what blood pressure alone would predict 4.

What the Aldosterone Blood Test Specifically Measures

The test quantifies the concentration of aldosterone circulating in serum or plasma, reported in nanograms per deciliter (ng/dL) or picomoles per liter (pmol/L). Most labs use liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay platforms. LC-MS/MS is considered the reference standard because immunoassays can cross-react with other steroids and overestimate levels by 10 to 20 percent in some patients 5.

The test is almost never interpreted alone. Clinicians pair it with plasma renin activity (PRA) or direct renin concentration (DRC) to calculate the aldosterone-to-renin ratio (ARR). The Endocrine Society's 2016 Clinical Practice Guideline recommends an ARR cutoff of 30 ng/dL per ng/mL/hr (when using PRA) as the threshold that should prompt confirmatory testing for primary aldosteronism 6.

A 24-hour urine aldosterone collection is the alternative specimen type. It captures total daily aldosterone excretion (reported as micrograms per 24 hours) and reduces the impact of moment-to-moment fluctuations. Urine collection is most often used during confirmatory salt-loading protocols rather than initial screening 6.

Normal Aldosterone Ranges

Reference intervals shift depending on posture, sodium intake, time of day, and the assay method used. These are commonly cited ranges from major reference laboratories.

Upright (seated or standing for 2 or more hours): 7 to 30 ng/dL. Supine (lying down for at least 30 minutes): 3 to 16 ng/dL. 24-hour urine: 6 to 25 mcg per 24 hours on an unrestricted sodium diet 7.

Posture matters because standing activates the RAAS. A patient measured supine will have substantially lower values than the same patient measured upright, which is why the Endocrine Society guidelines specify that screening should occur mid-morning after the patient has been upright for at least two hours 6.

Age also influences the range. Aldosterone levels decline with aging; healthy adults over 65 may run 30 to 50 percent lower than younger cohorts 8. Sodium intake plays an equally large role. A high-sodium diet suppresses aldosterone, while sodium restriction raises it. Labs typically note that reference ranges assume a normal-sodium diet (roughly 100 to 200 mEq sodium per day).

Dr. John W. Funder, lead author of the Endocrine Society guideline, has stated: "The ARR is recommended as the most reliable screening test for primary aldosteronism, but its interpretation requires standardized conditions, including posture, time of day, and medication status" 6.

When and Why Clinicians Order This Test

The primary clinical indication is screening for primary aldosteronism (PA). The Endocrine Society recommends screening in patients who meet any of the following criteria: sustained blood pressure above 150/100 mmHg, hypertension resistant to three conventional drugs, hypertension with spontaneous or diuretic-induced hypokalemia, hypertension with an adrenal incidentaloma, or hypertension with a family history of early-onset hypertension or stroke before age 40 6.

PA is far more common than previously assumed. A 2020 cross-sectional analysis of 1,015 normotensive and hypertensive participants found that the prevalence of biochemically confirmed PA ranged from 11.3 percent in stage 1 hypertension to 22 percent in treatment-resistant hypertension 9. That finding challenged the older textbook estimate of <1 percent prevalence.

Aldosterone testing also helps evaluate:

• Secondary aldosteronism: High aldosterone with high renin, pointing to conditions like renal artery stenosis, heart failure, or cirrhosis.
• Adrenal insufficiency: Low aldosterone with clinical signs such as hyperkalemia, salt wasting, and hypotension.
• Congenital adrenal hyperplasia: Specific enzyme deficiencies (21-hydroxylase, 11-beta-hydroxylase) alter aldosterone production in predictable patterns 10.

What High Aldosterone Means

Elevated aldosterone signals one of two broad categories. The distinction between them depends entirely on whether renin is suppressed or elevated.

Primary aldosteronism (high aldosterone, low renin). The adrenal glands overproduce aldosterone independently of the RAAS. The two most common subtypes are bilateral adrenal hyperplasia (about 60 percent of cases) and aldosterone-producing adenoma (about 35 percent). Rare causes include unilateral hyperplasia, adrenal carcinoma, and familial hyperaldosteronism types I through IV 6.

Patients with PA experience sodium retention, volume expansion, potassium wasting, and metabolic alkalosis. Hypokalemia is the classic textbook finding, but only 9 to 37 percent of PA patients present with low potassium. Normal potassium does not exclude the diagnosis 11.

The PASO study (Primary Aldosteronism Surgical Outcome), which followed 705 patients after adrenalectomy across 31 centers, reported complete biochemical success in 94 percent of cases and complete clinical success (blood pressure normalization without medication) in 37 percent 12.

Secondary aldosteronism (high aldosterone, high renin). Renin drives the aldosterone excess. Renal artery stenosis, decompensated heart failure, nephrotic syndrome, and cirrhosis with ascites all trigger this pattern. Treatment targets the underlying cause rather than aldosterone directly 2.

What Low Aldosterone Means

Low aldosterone creates the opposite clinical picture: sodium wasting, potassium retention, low blood volume, and a tendency toward hypotension. Several conditions produce this pattern.

Primary adrenal insufficiency (Addison disease). Autoimmune destruction of the adrenal cortex reduces both cortisol and aldosterone. Patients present with hyperkalemia, hyponatremia, hypotension, and fatigue. The incidence in Western countries is approximately 0.8 per 100,000 person-years 13.

Hyporeninemic hypoaldosteronism (type IV renal tubular acidosis). Common in diabetic nephropathy and chronic kidney disease. Renin production is impaired, leading to low aldosterone. Patients develop mild hyperkalemia and a non-anion-gap metabolic acidosis 14.

Drug-induced suppression. ACE inhibitors, angiotensin receptor blockers (ARBs), direct renin inhibitors, and heparin all lower aldosterone through different mechanisms. This is therapeutically intentional in heart failure and hypertension but must be accounted for during diagnostic testing 6.

Dr. William F. Young Jr., writing in the New England Journal of Medicine, noted: "Hypoaldosteronism is often overlooked in patients with unexplained hyperkalemia, particularly in those with diabetes mellitus and mild to moderate renal impairment" 15.

How to Lower Aldosterone

Lowering aldosterone is a treatment goal in primary aldosteronism, resistant hypertension, and heart failure. The approach depends on the underlying diagnosis.

Mineralocorticoid receptor antagonists. Spironolactone (starting dose 12.5 to 25 mg daily, titrated up to 100 mg) is the first-line medical therapy for bilateral adrenal hyperplasia. Eplerenone (starting dose 25 mg twice daily) is the alternative when spironolactone's anti-androgenic side effects (gynecomastia, breast tenderness, menstrual irregularities) are intolerable. In the RALES trial (N=1,663), spironolactone 25 mg daily reduced all-cause mortality by 30 percent in severe heart failure patients, driven in part by aldosterone blockade 16.

Surgery. For unilateral aldosterone-producing adenomas confirmed by adrenal vein sampling, laparoscopic adrenalectomy is the definitive treatment. The Endocrine Society recommends adrenal vein sampling (AVS) before surgery to confirm lateralization, since CT imaging alone misclassifies the source in up to 37.8 percent of cases 6.

Dietary sodium restriction. A high-sodium diet does not cause primary aldosteronism, but reducing sodium intake to <2,000 mg per day can partially mitigate the downstream effects of aldosterone excess on blood pressure 17.

Potassium supplementation. Maintaining serum potassium above 4.0 mEq/L helps counteract aldosterone-driven potassium wasting and reduces the risk of arrhythmia in PA patients awaiting definitive treatment 6.

How to Raise Aldosterone

Raising aldosterone is rarely a standalone therapeutic goal. When aldosterone is low because of adrenal insufficiency, the treatment is replacement with fludrocortisone, a synthetic mineralocorticoid.

Fludrocortisone. The standard replacement dose is 0.05 to 0.2 mg daily. The Endocrine Society's 2016 guideline on adrenal insufficiency recommends monitoring adequacy by tracking blood pressure (both supine and standing), serum potassium, and plasma renin activity. A renin level in the upper-normal range suggests appropriate mineralocorticoid replacement 18.

Correcting reversible causes. In hyporeninemic hypoaldosteronism from diabetic nephropathy, optimizing glycemic control and discontinuing drugs that suppress the RAAS (when clinically safe) may partially restore aldosterone production 14.

Addressing posture and volume status. Patients with orthostatic hypotension from low aldosterone benefit from increasing salt intake (if not contraindicated), wearing compression stockings, and elevating the head of the bed to stimulate overnight renin release 18.

Medications That Interfere with Aldosterone Testing

Testing accuracy depends heavily on medication status. The Endocrine Society guideline lists specific drugs that must be managed before screening.

Must be withdrawn (ideally 4 weeks before testing): Spironolactone, eplerenone, amiloride, triamterene, potassium-wasting diuretics (hydrochlorothiazide, furosemide, chlorthalidone), and licorice-derived products. These agents directly alter aldosterone or renin levels enough to produce false-positive or false-negative ARR results 6.

May be continued with caution: Verapamil slow-release and alpha-adrenergic blockers (doxazosin, prazosin) have minimal effects on the ARR and are recommended as interim antihypertensive therapy during the washout period 6.

Beta-blockers and central alpha-2 agonists (clonidine) suppress renin and can produce a falsely elevated ARR, mimicking primary aldosteronism. The guideline recommends withdrawal for at least two weeks when feasible 6.

Oral contraceptives containing estrogen also lower direct renin concentration while raising aldosterone-binding proteins, which can skew immunoassay results. Switching to a progestin-only method or using LC-MS/MS can reduce this interference 19.

Confirmatory Testing After a Positive Screen

A positive ARR screen is not a diagnosis. Confirmation requires demonstrating that aldosterone fails to suppress under conditions that should suppress it. The Endocrine Society recognizes four confirmatory protocols 6.

Oral sodium loading test. The patient consumes more than 200 mEq sodium per day for 3 days, then collects a 24-hour urine. Urinary aldosterone above 12 mcg per 24 hours (with urinary sodium above 200 mEq confirming adequate sodium loading) confirms autonomous aldosterone secretion.

Intravenous saline infusion test. Two liters of 0.9% saline are infused over 4 hours while the patient remains recumbent. Post-infusion plasma aldosterone above 10 ng/dL confirms the diagnosis; values between 5 and 10 ng/dL are indeterminate.

Fludrocortisone suppression test. The patient takes 0.1 mg fludrocortisone every 6 hours for 4 days with sodium chloride supplementation. An upright aldosterone above 6 ng/dL on day 4 confirms the diagnosis. This test is the most sensitive but logistically demanding and carries a risk of severe hypokalemia.

Captopril challenge test. The patient takes 25 to 50 mg captopril orally, with aldosterone measured at baseline and 1 to 2 hours later. Failure of aldosterone to suppress below 30 percent of baseline (or to fall below 8.5 ng/dL) supports PA. This test is the simplest to perform but has the lowest sensitivity 6.

Subtype Differentiation and Adrenal Vein Sampling

Once PA is confirmed, determining the subtype dictates treatment. Bilateral hyperplasia is managed medically; unilateral adenoma is managed surgically.

Adrenal vein sampling (AVS) is the gold standard for lateralization. A systematic review of 47 studies found that AVS changed the surgical decision in 37.8 percent of patients compared to CT alone 20. CT can miss sub-centimeter adenomas and, conversely, can identify non-functioning adrenal incidentalomas that have no connection to aldosterone production.

AVS requires catheterization of both adrenal veins, with cortisol measurements to confirm successful cannulation. A lateralization index (aldosterone/cortisol ratio from one side divided by the other) of 4:1 or greater indicates unilateral disease 6. The procedure is technically challenging, with reported bilateral cannulation success rates ranging from 43 to 97 percent depending on institutional experience 20.

For patients under age 35 with a clear unilateral adenoma on CT, spontaneous hypokalemia, and marked aldosterone excess, the 2016 guideline states that proceeding directly to adrenalectomy without AVS is reasonable 6.