Aldosterone: What Your Number Changes About Your Treatment

What Aldosterone Is and Why It Gets Measured

Aldosterone is a steroid hormone secreted by the zona glomerulosa of the adrenal cortex. Its primary job is to tell the kidneys to retain sodium and excrete potassium, which pulls water along and raises blood pressure. When the renin-angiotensin-aldosterone system (RAAS) is working correctly, aldosterone rises when blood pressure drops and falls when blood pressure is adequate.

Clinicians order a plasma aldosterone concentration (PAC) when a patient has hard-to-control hypertension, unprovoked hypokalemia, an adrenal incidentaloma, or symptoms consistent with adrenal insufficiency such as fatigue, salt craving, and orthostatic dizziness. The result almost never travels alone. It is always interpreted alongside plasma renin activity (PRA) or direct renin concentration (DRC) to calculate the aldosterone-to-renin ratio (ARR), which is the primary screening tool recommended by the 2016 Endocrine Society Clinical Practice Guideline on primary aldosteronism. [1]

How the Test Is Performed

Blood is drawn in the morning after the patient has been seated for 5 to 15 minutes. Posture matters: aldosterone can be 2 to 3 times higher standing than supine. [2] Most reference labs report PAC in ng/dL; some use pmol/L (multiply ng/dL by 27.7 to convert).

Medications that suppress the RAAS, including spironolactone, eplerenone, amiloride, and high-dose potassium supplements, should be held for four weeks before testing. Beta-blockers and NSAIDs can artificially lower renin, which falsely elevates the ARR. The Endocrine Society guideline specifically recommends switching to verapamil slow-release, hydralazine, prazosin, or doxazosin as bridge antihypertensives during the washout period. [1]

Units and Lab-Specific Variation

Reference intervals vary by laboratory. Mayo Clinic Laboratories reports a seated morning PAC reference of 3 to 21 ng/dL for adults not on confounding medications. Cleveland Clinic uses a similar range of 2 to 9 ng/dL for supine draws and 2 to 21 ng/dL for upright draws. Because posture and sodium intake shift results, always confirm which collection conditions your lab used before interpreting a borderline value.

Normal Aldosterone Range: What the Numbers Mean

A normal aldosterone result for a seated adult in the morning is approximately 3 to 21 ng/dL, though most healthy adults cluster between 5 and 12 ng/dL. [2] Outside that range, the clinical path branches sharply.

The number alone rarely drives a treatment decision. Context determines everything: the patient's sodium intake, potassium level, time of day, posture, concurrent medications, and the renin result drawn at the same time.

The Aldosterone-to-Renin Ratio Explained

The ARR is calculated by dividing PAC (in ng/dL) by PRA (in ng/mL/hr). An ARR above 30 with a PAC above 15 ng/dL meets the Endocrine Society's screening threshold for primary aldosteronism. [1] Some centers use a lower ARR cutoff of 20 when the PAC is above 20 ng/dL. A suppressed renin below 0.5 to 1.0 ng/mL/hr with a normal-to-high aldosterone is the hallmark pattern.

Why Potassium Changes the Interpretation

Hypokalemia suppresses aldosterone secretion even in autonomous-producing adenomas, which means a patient with an aldosterone-producing adenoma (APA) and severe hypokalemia may have a PAC that looks only modestly elevated. Correcting the potassium before re-drawing often reveals a higher true PAC and makes the ARR more clearly positive. The Endocrine Society guideline emphasizes potassium repletion prior to testing for exactly this reason. [1]

High Aldosterone: Causes, Diagnosis, and Treatment Changes

A PAC above 21 ng/dL with a suppressed renin almost always means primary aldosteronism (PA). PA affects an estimated 5 to 10% of all hypertensive patients, making it the most common secondary cause of hypertension. [3]

This is not a rare condition found only in academic centers. A 2020 analysis published in the Annals of Internal Medicine estimated that PA may account for about 11% of hypertension cases when systematic screening is applied, compared with only 1 to 2% when testing is reserved for hypokalemia alone. [4]

Confirming Primary Aldosteronism

A positive ARR screen requires confirmatory testing before treatment begins. Four tests are accepted by the Endocrine Society guideline:

1. Oral sodium loading test (200 mmol/day for 3 days; 24-hour urine aldosterone >12 mcg confirms PA)
2. Saline infusion test (2 L normal saline over 4 hours; post-infusion PAC >10 ng/dL confirms PA)
3. Fludrocortisone suppression test (0.1 mg every 6 hours for 4 days; standing PAC >6 ng/dL on day 4 confirms PA)
4. Captopril challenge (25 to 50 mg captopril orally; PAC >11 ng/dL at 1 to 2 hours confirms PA) [1]

The saline infusion test is the most widely used in outpatient endocrinology clinics in North America because it can be completed in a single visit.

Subtype Workup and the Surgical Decision

Once PA is confirmed, the next question is whether aldosterone is coming from one adrenal gland (unilateral, usually an APA) or both (bilateral adrenal hyperplasia, BAH). CT imaging misidentifies the source in up to 37.8% of cases, according to a pooled analysis of adrenal venous sampling (AVS) studies. [5] For this reason, AVS is the standard of care before any surgical referral in patients who are operative candidates.

The treatment pivot depends entirely on subtype:

• Unilateral APA confirmed by AVS: Laparoscopic adrenalectomy is the preferred treatment. Blood pressure normalizes completely in 30 to 72% of patients at 12 months, and hypertension improves in more than 90%, per a 2020 systematic review in The Lancet Diabetes and Endocrinology. [6]
• Bilateral adrenal hyperplasia or patient not a surgical candidate: Mineralocorticoid receptor antagonist (MRA) therapy. Spironolactone 25 mg/day is the first-line agent, titrated to a maximum of 100 mg/day based on blood pressure and potassium response. Eplerenone 25 to 50 mg twice daily is used when spironolactone causes intolerable anti-androgenic effects (gynecomastia, menstrual irregularity). [1]

What Happens to Your Other Medications

Starting an MRA changes the entire antihypertensive regimen. ACE inhibitors and ARBs must be monitored closely because combining them with spironolactone raises serum potassium meaningfully, particularly in patients with an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m². Potassium should be checked at 1 week, 4 weeks, and 3 months after initiating MRA therapy. Blood pressure often drops enough within 4 to 8 weeks to allow dose reduction or discontinuation of one or more prior antihypertensive agents.

Low Aldosterone: Causes, Diagnosis, and Treatment Changes

A PAC below 3 to 5 ng/dL, especially with high renin and low cortisol, points toward adrenal insufficiency (AI), either primary (Addison disease) or secondary (from pituitary or hypothalamic pathology). [7]

Isolated hypoaldosteronism without cortisol deficiency also occurs. Hyporeninemic hypoaldosteronism is the most common cause of type 4 renal tubular acidosis and is seen most often in diabetic nephropathy and NSAIDs overuse.

Distinguishing Primary from Secondary Adrenal Insufficiency

In primary AI, both aldosterone and cortisol are low, while renin is high (the adrenal gland cannot respond). In secondary AI, ACTH deficiency suppresses cortisol but the zona glomerulosa is partially preserved, so aldosterone may be low-normal rather than severely depressed. This distinction matters because primary AI requires fludrocortisone replacement while secondary AI typically does not. [7]

The standard diagnostic test is the short cosyntropin (ACTH) stimulation test: 250 mcg cosyntropin IV or IM, with cortisol drawn at 0, 30, and 60 minutes. A peak cortisol below 18 mcg/dL at any point is consistent with AI per Endocrine Society criteria. [7]

Fludrocortisone: The Treatment Pivot for Low Aldosterone

Confirmed primary AI triggers immediate mineralocorticoid replacement with fludrocortisone acetate 0.05 to 0.2 mg orally once daily, in addition to hydrocortisone 15 to 25 mg/day in divided doses for glucocorticoid replacement. [7] The Endocrine Society's 2016 guideline on adrenal insufficiency states: "We recommend that all patients with primary adrenal insufficiency receive mineralocorticoid replacement with fludrocortisone (starting dose 0.05 to 0.1 mg/day) together with adequate dietary sodium." [7]

Dose adequacy is monitored by PAC itself (target: low-normal range), PRA (target: upper half of normal), blood pressure, and absence of pedal edema. Over-replacement causes hypertension and hypokalemia; under-replacement causes postural hypotension and sodium wasting.

Hyporeninemic Hypoaldosteronism (Type 4 RTA)

Patients with diabetes, chronic kidney disease (CKD), or both often develop mildly low aldosterone due to low renin, not adrenal failure. The hallmark is hyperkalemia out of proportion to the degree of CKD, with a normal anion gap metabolic acidosis. Treatment focuses on the underlying cause (tight glycemic control, stopping offending drugs) and may include low-dose fludrocortisone 0.1 mg/day or a loop diuretic to drive renal potassium excretion. [8]

How to Lower Aldosterone: Lifestyle and Medication Strategies

High aldosterone from bilateral hyperplasia or mild PA can often be partially controlled through targeted interventions, though autonomous secretion from an APA rarely responds enough to lifestyle alone to avoid medication.

Dietary Sodium Restriction

Lowering sodium intake to below 2,300 mg/day activates the RAAS in normal physiology, but in PA the relationship is blunted. Moderate restriction still helps reduce total volume load and blood pressure. The American Heart Association's 2021 dietary sodium guideline recommends a target of 1,500 mg/day for hypertensive patients. [9]

Mineralocorticoid Receptor Antagonists

Spironolactone and eplerenone block aldosterone's receptor directly. A 2018 Cochrane review of spironolactone for primary aldosteronism found that patients on spironolactone achieved systolic blood pressure reductions of approximately 25 mmHg compared with baseline over a mean follow-up of 12 months. [10] Eplerenone is more selective for the mineralocorticoid receptor and carries a lower rate of sexual side effects, though it costs significantly more and requires twice-daily dosing.

Potassium Supplementation as an Adjunct

Adequate potassium intake (target serum K+ 4.0 to 4.5 mEq/L) can modestly suppress aldosterone secretion. A diet rich in potassium from whole foods (bananas, avocado, leafy greens) is a reasonable first step, but most PA patients need oral potassium chloride supplementation of 40 to 80 mEq/day until an MRA is started.

How to Raise Aldosterone: When and How Replacement Is Given

Low aldosterone requires a different approach depending on the cause and whether renin is high or low.

Fludrocortisone for Primary Adrenal Insufficiency

As noted above, fludrocortisone 0.05 to 0.2 mg/day is the standard replacement. Patients need more during illness, surgery, or heat exposure, because sweating and gastrointestinal losses increase sodium and fluid demand. The Endocrine Society advises patients to carry a medical alert identification and an emergency injection kit of hydrocortisone 100 mg IM for adrenal crisis prevention. [7]

Salt and Volume Expansion for Mild Cases

In hyporeninemic hypoaldosteronism without frank AI, simply increasing dietary sodium and correcting the underlying cause (optimizing diabetes management, stopping NSAIDs) may normalize electrolytes without hormone replacement. [8]

Avoiding Drugs That Suppress the RAAS

Patients with borderline-low aldosterone who are asymptomatic should avoid ACE inhibitors, ARBs, direct renin inhibitors, and NSAIDs if clinically feasible, because all four drug classes further suppress aldosterone synthesis or action. Beta-blockers reduce renin release, which secondarily lowers aldosterone, and should also be reviewed in this population.

Medications That Interfere With Aldosterone Testing

Getting a reliable aldosterone result requires careful medication management. The following drug classes alter PAC, PRA, or both, and must be considered before interpreting any result.

| Drug Class | Effect on PAC | Effect on PRA | Net Effect on ARR | |---|---|---|---| | Spironolactone / eplerenone | Raise PAC (reflex) | Raise PRA | Falsely lower ARR | | ACE inhibitors / ARBs | Lower PAC (modestly) | Raise PRA | Falsely lower ARR | | Beta-blockers | Lower PAC (modestly) | Suppress PRA | Falsely raise ARR | | NSAIDs | Lower PAC (modestly) | Suppress PRA | Falsely raise ARR | | Oral contraceptives | Variable | Lower PRA | Falsely raise ARR | | Potassium-wasting diuretics | Raise PAC (reflex) | Raise PRA | Variable |

The Endocrine Society guideline recommends a minimum four-week washout for spironolactone, eplerenone, and amiloride, and a two-week washout for all other interfering medications. [1]

Aldosterone in Specific Populations

Pregnancy

Aldosterone rises two- to threefold during normal pregnancy due to placental estrogen stimulating angiotensinogen production. A PAC of 40 to 100 ng/dL in the third trimester can be physiologically normal. PA during pregnancy requires careful management because spironolactone is contraindicated (anti-androgenic effects on the fetal male genitalia). Eplerenone has been used off-label in case series, and nifedipine with potassium supplementation is often used to bridge to delivery. [11]

Older Adults

Renin and aldosterone both decline with age due to reduced renal renin secretion. Older patients, especially those with CKD or diabetes, are predisposed to hyporeninemic hypoaldosteronism and hyperkalemia. Starting an ACE inhibitor or ARB in a patient over 70 with an eGFR below 45 mL/min/1.73 m² warrants baseline and follow-up potassium and aldosterone assessment within 1 to 2 weeks.

Patients on Telehealth TRT or HRT

Testosterone and estrogen both modulate the RAAS. Supraphysiologic testosterone can increase hematocrit and blood pressure, indirectly affecting renin and aldosterone output. Exogenous estrogen (oral formulation specifically) raises angiotensinogen and can drive a secondary increase in aldosterone. Patients on telehealth hormone protocols who develop new-onset hypertension or hypokalemia should have PAC, PRA, and a basic metabolic panel drawn before adding or escalating antihypertensive medications.