Aldosterone: How to Interpret Your Result

What Is Aldosterone and Why Is It Tested?

Aldosterone is a mineralocorticoid hormone secreted by the zona glomerulosa of the adrenal cortex. Its job is to signal the kidneys to retain sodium and excrete potassium, which in turn raises blood volume and blood pressure. Clinicians order it when a patient has resistant hypertension, unexplained low potassium, or an incidentally discovered adrenal mass.

The Renin-Angiotensin-Aldosterone System

Aldosterone does not act alone. Renin, released by the kidney when blood pressure drops, cleaves angiotensinogen into angiotensin I, which converts to angiotensin II, which then stimulates aldosterone release. Testing aldosterone in isolation misses half the picture, which is why most guidelines recommend measuring plasma renin activity (PRA) or direct renin concentration (DRC) at the same time. The Endocrine Society's 2016 Clinical Practice Guideline on Primary Aldosteronism states: "We recommend using the aldosterone-to-renin ratio (ARR) as a case-detection test in patients with hypertension and hypokalemia, adrenal incidentaloma, or early-onset hypertension." [1]

Specimen Type and Posture

Aldosterone is measured in serum or plasma, and sometimes in a 24-hour urine collection. The patient's posture at the time of the draw changes the result significantly. Levels in an upright patient are typically 2 to 4 times higher than in someone who has been lying down for two hours. [2] Most outpatient draws are done after the patient has been seated or standing for at least 15 minutes, and the lab report should reflect that.

Normal Aldosterone Range

Reference ranges differ by lab, by posture, and by whether the sample is serum or urine, so always compare your result to the range printed on your own lab report.

Serum Reference Ranges

For adults, the widely cited reference intervals are:

• Supine (recumbent): 3 to 16 ng/dL
• Upright (seated or standing): 4 to 31 ng/dL

These figures align with the ranges reported by Mayo Clinic Laboratories and Cleveland Clinic for adult patients not on interfering medications. [3] Converting to SI units: multiply ng/dL by 27.7 to get pmol/L, so 31 ng/dL equals roughly 859 pmol/L.

Urine Reference Ranges

A 24-hour urine aldosterone collected during high sodium intake (greater than 200 mEq/day) should normally be below 12 mcg/24 hours. Values above that threshold on a high-salt diet are a positive confirmatory result for primary aldosteronism per Endocrine Society criteria. [1]

The Aldosterone-to-Renin Ratio

A single aldosterone value cannot diagnose primary aldosteronism on its own. The ARR combines aldosterone (ng/dL) with PRA (ng/mL/hr). An ARR above 30 has a reported sensitivity of roughly 64 to 90% and specificity of 61 to 85% for primary aldosteronism depending on the cutoff used. [4] Some centers use a cutoff of 20 when PRA is expressed as ng/mL/hr and aldosterone as ng/dL. The Endocrine Society guideline recommends confirming any positive ARR with at least one of four confirmatory tests before moving to adrenal imaging. [1]

What a High Aldosterone Result Means

A serum aldosterone above 31 ng/dL on an upright draw, combined with an ARR above 30, is the starting point for a primary aldosteronism workup. PA is not rare. A 2020 meta-analysis in the Journal of the American Heart Association (N=3,801 hypertensive patients) estimated the prevalence of PA at approximately 6.1% across primary care settings, rising to more than 20% in resistant hypertension clinics. [5]

Primary Aldosteronism

Primary aldosteronism means the adrenal gland is making too much aldosterone independent of renin signaling. The two main subtypes are unilateral adrenal adenoma (Conn syndrome, accounting for roughly 35% of PA cases) and bilateral adrenal hyperplasia (accounting for about 60%). [1] The distinction matters because an adenoma can be removed surgically, while hyperplasia is managed medically.

Symptoms are often absent or nonspecific. Hypertension is present in virtually all cases. Hypokalemia (potassium below 3.5 mEq/L) occurs in only 9 to 37% of confirmed PA patients, so a normal potassium does not rule out the diagnosis. [1]

Confirmatory Testing Steps

After a positive ARR, the Endocrine Society recommends one of these confirmatory tests: [1]

1. Oral sodium loading (200 mEq/day for 3 days, then 24-hour urine aldosterone)
2. Saline infusion test (2 liters of 0.9% NaCl over 4 hours IV; PA is confirmed if post-infusion aldosterone exceeds 10 ng/dL)
3. Fludrocortisone suppression test
4. Captopril challenge test

If confirmatory testing is positive, CT of the adrenal glands follows. Adrenal vein sampling (AVS) is the gold standard for lateralizing PA before surgery and is recommended whenever a patient is a surgical candidate. [1]

Secondary Causes of High Aldosterone

When both aldosterone and renin are elevated, the cause is secondary aldosteronism. Common drivers include renal artery stenosis, heart failure, cirrhosis, and nephrotic syndrome. In these cases, the kidney signals low perfusion, renin climbs, and aldosterone follows. Treatment targets the underlying condition, not the aldosterone itself. [6]

What a Low Aldosterone Result Means

A serum aldosterone below 3 to 4 ng/dL (supine) paired with elevated renin points toward adrenal insufficiency. Low aldosterone with low renin suggests hyporeninemic hypoaldosteronism, a pattern common in type 2 diabetes and chronic kidney disease.

Adrenal Insufficiency

Primary adrenal insufficiency (Addison disease) destroys the zona glomerulosa along with the cortisol-producing layers of the adrenal cortex. Aldosterone, cortisol, and androgens all fall. A landmark NIH study estimated the prevalence of Addison disease at 100 to 140 cases per million in Western populations. [7] The clinical picture includes hypotension, hyperkalemia, hyponatremia, and fatigue.

Diagnosis involves an 8 a.m. Cortisol, ACTH stimulation testing, and measurement of plasma aldosterone and renin. The Endocrine Society's 2016 guideline on adrenal insufficiency recommends the 250-mcg cosyntropin stimulation test as the standard first-line diagnostic tool. [8]

Hyporeninemic Hypoaldosteronism

This pattern shows low aldosterone alongside low renin activity, meaning the problem starts upstream in the kidney's renin-producing cells. It is especially common in diabetic nephropathy. Patients typically present with hyperkalemia out of proportion to their kidney function. NSAIDs, calcineurin inhibitors, and beta-blockers can all suppress renin and precipitate this picture. [9]

Drug-Induced Low Aldosterone

ACE inhibitors and ARBs lower aldosterone by blocking the angiotensin II signal. Heparin and low-molecular-weight heparin directly suppress adrenal aldosterone synthesis with as little as 6 days of exposure. If a patient on any of these agents has a low aldosterone result, the medication effect must be considered before attributing the finding to a primary adrenal problem.

Medications That Interfere With Aldosterone Testing

Several drugs change aldosterone or renin enough to produce false-positive or false-negative results. The Endocrine Society recommends a washout period before confirmatory testing: [1]

| Medication Class | Effect on Aldosterone/Renin | Recommended Washout | |---|---|---| | Spironolactone, eplerenone | Raises renin, raises aldosterone | 4 to 6 weeks | | ACE inhibitors, ARBs | Raises renin, lowers aldosterone | 2 weeks | | Beta-blockers | Lowers renin (may falsely lower ARR) | 2 weeks | | Dihydropyridine calcium channel blockers | Minimal effect; acceptable during testing | None required | | Oral contraceptives | May lower DRC (less effect on PRA) | 4 weeks if using DRC |

Verapamil (non-dihydropyridine) and doxazosin are considered the least interfering antihypertensives during aldosterone evaluation and are often substituted during the washout period. [1]

How to Lower High Aldosterone

Treatment depends on whether the cause is unilateral or bilateral.

Surgical Approach for Adrenal Adenoma

Unilateral laparoscopic adrenalectomy is the definitive treatment for a unilateral adenoma confirmed by AVS. The SPARTACUS trial (N=200) compared AVS-guided care versus CT-guided care and found that blood pressure outcomes were similar at 1 year, though AVS correctly identified bilateral disease in a proportion of patients whose CT suggested unilateral adenoma. [10] After successful surgery, 30 to 72% of patients achieve complete biochemical resolution, meaning aldosterone and potassium normalize without medication. [1]

Mineralocorticoid Receptor Antagonists

For bilateral adrenal hyperplasia or patients who are not surgical candidates, spironolactone is the first-line drug. The typical starting dose is 12.5 to 25 mg/day, titrated to blood pressure control and potassium normalization, with a maximum of 100 to 200 mg/day. Eplerenone (25 to 50 mg twice daily) is an alternative with fewer anti-androgenic side effects, though it is somewhat less potent per milligram. [1]

A 2021 analysis in Hypertension (N=602 PA patients followed for a median 7.4 years) found that mineralocorticoid receptor antagonist therapy reduced cardiovascular event rates to levels comparable to essential hypertension controls, provided blood pressure was well-controlled. [11]

Dietary Sodium Restriction

Reducing sodium intake below 2,300 mg/day reduces the physiologic stimulus for aldosterone secretion in secondary aldosteronism. For primary aldosteronism, sodium restriction alone cannot normalize aldosterone production but does reduce its downstream blood pressure effect and potassium loss. The American Heart Association recommends below 1,500 mg/day for patients with resistant hypertension. [12]

How to Raise Low Aldosterone

Fludrocortisone Replacement

For primary adrenal insufficiency, fludrocortisone is the standard mineralocorticoid replacement. The usual adult dose is 50 to 200 mcg once daily in the morning, adjusted based on blood pressure, serum potassium, and plasma renin activity. The Endocrine Society guideline states: "We suggest monitoring fludrocortisone replacement by clinical assessment of postural hypotension and by measuring serum electrolytes and plasma renin activity or concentration." [8] Renin in the upper-normal range generally indicates adequate replacement.

Sodium and Fluid Intake

Patients on fludrocortisone are encouraged to maintain a liberal sodium intake (at least 3 to 4 grams of sodium per day) to support blood volume. During illness, fever, or surgery, the stress-dosing protocol for hydrocortisone also reduces aldosterone-related losses; patients should be counseled to increase fluid and sodium intake and contact their care team early. [8]

Managing Hyporeninemic Hypoaldosteronism

When low renin drives low aldosterone in a diabetic or CKD patient, small doses of fludrocortisone (50 to 100 mcg/day) can correct hyperkalemia. The tradeoff is sodium retention and possible blood pressure elevation, so dose titration requires close monitoring of potassium, blood pressure, and renal function. [9] Dietary potassium restriction below 2,000 mg/day is often added as an adjunct.

Collecting an Aldosterone Sample: Practical Preparation

Getting an accurate aldosterone result requires some preparation on the patient's part.

• Posture before the draw. Sit or stand for at least 15 to 30 minutes before the venipuncture. Document the position on the lab order so the result can be compared to the correct reference range.
• Salt intake. Avoid deliberate salt restriction for at least three days before the draw. A very low-sodium diet raises renin and aldosterone and can produce a false-positive ARR.
• Time of day. Draw early in the morning (between 8 and 10 a.m.) when the renin-angiotensin-aldosterone system is near its daily peak. Afternoon draws tend to produce lower aldosterone values.
• Medication review. Confirm with your clinician whether any antihypertensives, diuretics, or oral contraceptives need to be paused in advance.
• Potassium correction. The Endocrine Society recommends correcting hypokalemia before aldosterone testing because low potassium independently suppresses aldosterone secretion and can mask a positive ARR. [1]

An uncorrected potassium below 3.0 mEq/L on the day of the draw should prompt specimen collection to be postponed or results to be interpreted with caution.