What is the best management approach for primary aldosteronism?

Management of Primary Aldosteronism

For unilateral disease, laparoscopic adrenalectomy is the definitive treatment, curing hypertension in approximately 50% and improving blood pressure in virtually 100% of patients; for bilateral disease, spironolactone (starting 25-100 mg daily) is first-line medical therapy. 1, 2

Diagnostic Confirmation Before Treatment

Before initiating treatment, you must complete the three-phase diagnostic workup:

• Screen with aldosterone-to-renin ratio (ARR ≥30 with plasma aldosterone ≥10 ng/dL) 1
• Confirm with saline suppression test or oral sodium loading (failure to suppress aldosterone below 5 ng/dL confirms autonomous secretion) 1
• Determine subtype with adrenal venous sampling (AVS) to distinguish unilateral from bilateral disease—this step is mandatory before offering surgery 1, 3

Critical caveat: CT imaging alone is insufficient for treatment decisions, as adenomas on imaging can represent bilateral hyperplasia and false positives are common; AVS is essential except in patients <40 years with a single affected gland on imaging 1, 4

Treatment Algorithm Based on Subtype

Unilateral Disease (Aldosterone-Producing Adenoma or Unilateral Hyperplasia)

Laparoscopic unilateral adrenalectomy is the treatment of choice 1, 2, 3:

• Improves blood pressure in virtually 100% of patients 1, 2
• Achieves complete cure of hypertension in approximately 50% of cases 1, 2
• Normalizes hypokalemia in all patients 1
• Reduces cardiovascular and renal complications by reversing aldosterone-mediated organ damage 2

For patients unsuitable for surgery, use mineralocorticoid receptor antagonists as described below 3, 5

Bilateral Disease (Idiopathic Hyperaldosteronism)

Medical therapy with mineralocorticoid receptor antagonists is the cornerstone of treatment 1, 3:

First-Line: Spironolactone 3, 5

• Starting dose: 25-100 mg daily (single or divided doses) 5
• Titration: Can increase to 50 mg daily after tolerating 25 mg; doses >100 mg/day generally provide no additional benefit 5
• For primary aldosteronism specifically: 100-400 mg daily for long-term maintenance 5
• Monitoring: Check potassium and creatinine at 3 days, 1 week, then monthly for 3 months, then every 3 months if stable 3

Alternative: Eplerenone 3

• Indication: Use for patients who develop gynecomastia, breast tenderness, or sexual dysfunction on spironolactone 3
• Dosing: 50-100 mg daily in 1-2 doses 3
• Efficacy: Equal effectiveness to spironolactone for blood pressure control 3

Safety Requirements and Monitoring

Before Initiating Mineralocorticoid Receptor Antagonists 3

• Verify serum potassium ≤5.0 mEq/L 3
• Confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 3
• Discontinue potassium supplements 3

Contraindications and Drug Interactions 3

Avoid combining with:

• Potassium supplements or potassium-sparing diuretics (increased hyperkalemia risk) 3
• ACE inhibitors or ARBs without close monitoring (increased hyperkalemia risk) 3
• NSAIDs or COX-2 inhibitors (increased hyperkalemia and renal dysfunction risk) 3

Special Populations 5

• eGFR 30-50 mL/min: Consider initiating at 25 mg every other day due to hyperkalemia risk 5
• Cirrhosis: Initiate therapy in hospital setting with slow titration 5

Special Consideration: Familial Hyperaldosteronism Type 1

For glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1), low-dose dexamethasone is the recommended treatment rather than surgery or standard mineralocorticoid receptor antagonists 3

Treatment Goals and Outcomes

The primary aims of treatment are 2:

• Normalize blood pressure 2
• Normalize excessive aldosterone production 2
• Reduce cardiovascular and renal comorbidities (patients have 12-fold increased risk of target organ damage) 2
• Improve quality of life and reduce mortality 6

Important: Delayed diagnosis and treatment may lead to irreversible vascular remodeling and target organ damage, resulting in residual hypertension even after appropriate treatment 3. The toxic effects of aldosterone produce widespread tissue fibrosis and kidney damage beyond what occurs from hypertension alone, but these effects are often reversible with timely treatment 2

Common Pitfalls to Avoid

• Do not rely on hypokalemia as a marker for disease severity or treatment urgency—it is absent in 50% of cases, yet organ damage still occurs 2, 3
• Do not proceed to surgery based on CT findings alone—AVS is mandatory to prevent unnecessary adrenalectomy (up to 25% would undergo inappropriate surgery) 1
• Do not use mineralocorticoid receptor antagonists in patients with significant renal dysfunction (eGFR <30 mL/min) without extreme caution 3