What is the best management approach for primary hyperaldosteronism?

Management of Primary Hyperaldosteronism

The optimal management of primary hyperaldosteronism depends critically on whether the disease is unilateral or bilateral: unilateral disease should be treated with laparoscopic adrenalectomy (which cures hypertension in ~50% and improves blood pressure in virtually 100% of patients), while bilateral disease requires lifelong mineralocorticoid receptor antagonist therapy with spironolactone or eplerenone. 1

Why This Matters: The Stakes Are High

Primary aldosteronism is far from benign—it causes substantially worse outcomes than primary hypertension at equivalent blood pressure levels. Patients face a 3.7-fold increase in heart failure, 4.2-fold increase in stroke, 6.5-fold increase in myocardial infarction, and 12.1-fold increase in atrial fibrillation compared to matched primary hypertension patients. 1 The good news: these deleterious effects are often reversible with appropriate treatment. 1

Step 1: Confirm the Diagnosis

Screening

• Use the aldosterone-to-renin activity ratio as your screening test—it's the most accurate and reliable method available. 1
• A ratio >30 (with aldosterone in ng/dL and renin activity in ng/mL/h) suggests primary aldosteronism. 1
• Critical caveat: The plasma aldosterone concentration must be ≥10 ng/dL to interpret a positive test, as very low renin levels can falsely elevate the ratio. 1

Pre-test Preparation

Before testing, ensure: 1

• Unrestricted salt intake
• Normal serum potassium
• Mineralocorticoid receptor antagonists withdrawn for ≥4 weeks

Confirmation Testing

• Perform a confirmatory test (intravenous saline suppression test or oral salt-loading test) before proceeding to subtype differentiation. 1

Step 2: Determine Unilateral vs. Bilateral Disease

This is the critical decision point that determines treatment strategy. 1

Adrenal Venous Sampling

• Adrenal venous sampling is the gold standard for distinguishing unilateral from bilateral aldosterone hypersecretion. 1
• Perform this procedure if the patient is a surgical candidate and agrees that surgery would be desirable. 1
• Exception: In patients <40 years with imaging showing only one affected gland, you may reasonably skip adrenal venous sampling, as bilateral hyperplasia is rare in this population. 1

Imaging Considerations

• CT or MRI imaging alone is not reliable for determining lateralization—don't skip adrenal venous sampling based on imaging alone in most cases. 1
• In the 2024 ESC guidelines, functional imaging with radiolabeled tracers is mentioned as an alternative to adrenal venous sampling in sporadic forms. 1

Step 3: Treatment Based on Subtype

For Unilateral Disease: Surgery First

Unilateral laparoscopic adrenalectomy is the treatment of choice. 1

Outcomes you can expect: 1

• Blood pressure improvement in virtually 100% of patients
• Complete cure of hypertension in approximately 50% of patients
• Reversal of left ventricular hypertrophy
• Reduction in cardiovascular and renal complications

When to consider medical therapy instead: 1

• Older patients with significant comorbidities
• Patients who decline surgery

For Bilateral Disease: Medical Management

Spironolactone is the first-line agent. 1, 2

Dosing algorithm: 1, 2

• Start with 50-100 mg once daily
• Titrate up to 300-400 mg daily if needed for blood pressure control
• For primary hyperaldosteronism specifically, FDA labeling supports 100-400 mg daily 2

Alternative: Eplerenone 1

• Use when spironolactone causes intolerable side effects (particularly gynecomastia and erectile dysfunction in men) 1
• Less potent than spironolactone and requires twice-daily dosing 1
• Typical dose: 50-100 mg daily 3

Emerging options: 1

• Non-steroidal MRAs (finerenone, exarenone) are being tested
• Aldosterone synthase inhibitor (baxdrostat) shows promise in resistant hypertension

Additional Antihypertensive Therapy

If blood pressure remains uncontrolled on maximum MRA doses: 3

• Add potassium-sparing diuretics (amiloride or triamterene)
• Or add calcium channel antagonists

Step 4: Monitoring During Treatment

Essential monitoring parameters: 4

• Serum potassium, sodium, and creatinine at initiation and with each dose adjustment
• Blood pressure at each visit
• Fluid status assessment

Common pitfall: Hyperkalemia can develop, especially in patients with reduced kidney function. 2 In heart failure patients on spironolactone 25 mg daily who develop hyperkalemia, reduce to 25 mg every other day. 2

Special Consideration: Familial Forms

Glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1) is unique: 1

• Can be corrected with low-dose dexamethasone
• Safe during pregnancy
• Requires family history and genetic testing for diagnosis 1

Critical Timing Issue

Early diagnosis and treatment are crucial. 1 Delayed diagnosis leads to vascular remodeling that can cause persistent hypertension even after successful treatment—whether surgical or medical. The rate of cure is higher when diagnosis is made early in the disease course. 1

Who Should You Screen?

Target these high-risk populations: 1

• Patients with resistant hypertension (20% prevalence in this group)
• Adrenal incidentaloma discovered on imaging
• Early-onset hypertension or stroke at young age
• Unprovoked or excessive hypokalemia
• Stage 2 hypertension (≥160/100 mmHg)