What are the latest recommendations for primary aldosteronism treatment according to the 2025 guidelines?

What's New in the 2025 Approach to Primary Aldosteronism

The 2025 guidelines emphasize aggressive screening of high-risk hypertensive patients, with primary aldosteronism now recognized in up to 20% of resistant hypertension cases, making routine screening in this population a priority. 1, 2

Key Updates in Screening Approach

Expanded Screening Indications

The American College of Cardiology now recommends screening for primary aldosteronism in:

• Resistant hypertension (blood pressure uncontrolled on 3 medications including a diuretic) 1, 2
• Severe hypertension (BP >180/110 mmHg) 2
• Spontaneous or diuretic-induced hypokalemia 1
• Incidentally discovered adrenal mass 1, 2
• Family history of early-onset hypertension or stroke at age <40 years 1, 2

Critical pitfall to avoid: Do not rely on hypokalemia as a screening trigger—it is absent in 50% of primary aldosteronism cases and has low negative predictive value. 1, 2

Screening Test Protocol

• Use the plasma aldosterone-to-renin ratio (ARR) as the initial screening test 1, 2
• Positive screening criteria: ARR ≥30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10-15 ng/dL 1, 2
• Collect blood in the morning, with patient seated for 5-15 minutes after being out of bed for 2 hours 2
• Ensure patients are potassium-replete before testing, as hypokalemia suppresses aldosterone production 2

Medication Management Before Testing

• Stop when feasible: Beta-blockers, centrally acting drugs, and diuretics (cause false-positive results by suppressing renin) 2
• Safe alternatives: Long-acting calcium channel blockers and alpha-receptor antagonists minimally interfere with ARR 2
• Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing 2
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 2

Confirmatory Testing Requirements

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion. 1, 2

Confirmatory Test Options

• Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis 1
• Oral sodium loading test: 24-hour urine aldosterone measurement with unrestricted salt intake 1, 2
• Fludrocortisone suppression test: Alternative confirmatory option 2

All confirmatory testing should be performed with unrestricted salt intake and normal serum potassium levels. 1, 2

Subtype Determination: Critical for Treatment Selection

Imaging First

• Non-contrast CT scan of adrenal glands is the initial imaging modality 2
• Warning: CT findings alone are insufficient for treatment decisions—adenomas on imaging can represent hyperplasia, and false positives are common due to nodular hyperplasia 2

Adrenal Venous Sampling (AVS)

Adrenal venous sampling is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease. 1, 2

• Exception: AVS can be bypassed in patients <40 years when imaging shows a single affected gland, as bilateral hyperplasia is rare in this population 2
• Rationale: Up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 2
• AVS should be performed in specialized centers 1

Referral Pathway

All patients with confirmed primary aldosteronism should be referred to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 2

Treatment Algorithm Based on Subtype

Unilateral Disease (50% of cases)

Laparoscopic unilateral adrenalectomy is the treatment of choice for unilateral disease. 1, 2

Outcomes:

• Improves blood pressure in virtually 100% of patients 1
• Achieves complete cure of hypertension in approximately 50% 1
• Normalizes hypokalemia 2
• Improves cardiac and kidney function parameters 2

For non-surgical candidates: Medical therapy with mineralocorticoid receptor antagonists 1

Bilateral Disease (50% of cases)

Mineralocorticoid receptor antagonists (MRAs) are the cornerstone of treatment for bilateral disease. 1

First-Line: Spironolactone

• Starting dose: 25 mg once daily in patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m² 3
• Titration: May increase to 50 mg once daily as tolerated 3
• For primary hyperaldosteronism specifically: FDA-approved dosing is 100-400 mg daily 3
• Long-term maintenance: Use lowest effective dosage 3

Second-Line: Eplerenone

Eplerenone 50-100 mg daily is recommended for patients who develop gynecomastia, breast tenderness, or sexual dysfunction on spironolactone, with equal effectiveness for blood pressure control. 1

• Fewer anti-androgenic side effects compared to spironolactone 1
• Equally effective for blood pressure control in bilateral idiopathic hyperaldosteronism 1

Special Case: Familial Hyperaldosteronism Type 1

Low-dose dexamethasone treatment is recommended for familial hyperaldosteronism type 1 (glucocorticoid-remediable). 1

Safety Monitoring Protocol for MRA Therapy

Pre-Treatment Requirements

• Verify serum potassium ≤5.0 mEq/L 1
• Confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 1
• Discontinue potassium supplements 1

Monitoring Schedule

The American Heart Association recommends checking potassium and creatinine at:

• 3 days after initiation 1
• 1 week after initiation 1
• Monthly for the first 3 months 1
• Every 3 months thereafter if stable 1

Critical Drug Interactions to Avoid

Do not combine aldosterone antagonists with: 1

• Potassium supplements or potassium-sparing diuretics
• ACE inhibitors or ARBs without close monitoring
• NSAIDs or COX-2 inhibitors

All combinations increase risk of hyperkalemia and renal dysfunction. 1

Renal Impairment Considerations

• Use MRAs with caution in patients with eGFR <45 mL/min 1
• For eGFR 30-50 mL/min: Consider initiating spironolactone at 25 mg every other day due to hyperkalemia risk 3
• For patients who develop hyperkalemia on 25 mg daily: Reduce to 25 mg every other day 3

Clinical Outcomes and Importance of Early Treatment

Delayed diagnosis and treatment may lead to irreversible vascular remodeling and target organ damage, resulting in residual hypertension even after appropriate treatment. 1

Primary aldosteronism is associated with:

• Excess cardiovascular complications 1
• Renal complications 1
• Metabolic abnormalities 1

Targeted treatment with either surgery or MRAs effectively corrects metabolic abnormalities, reverses subclinical organ damage, and reduces cardiovascular and renal disease progression. 1

Major Diagnostic Pitfalls in 2025 Guidelines

1. Only 2-4% of eligible patients are currently being screened—screening rates remain unacceptably low 2
2. Normal potassium does not exclude primary aldosteronism—present in only 50% of cases 1, 2
3. Never proceed to surgery based on CT findings alone—AVS is essential for lateralization 2
4. Failure to withdraw interfering medications leads to false results 2
5. Inadequate monitoring for hyperkalemia when initiating MRA therapy 1