In an adult patient with hypertension and possible hypokalemia, how should primary aldosteronism be managed?

Treatment of Primary Aldosteronism

Immediate Treatment Decision Based on Disease Laterality

Laparoscopic unilateral adrenalectomy is the definitive treatment for unilateral disease (aldosterone-producing adenoma or unilateral hyperplasia), achieving blood pressure improvement in virtually 100% of patients and complete hypertension cure in approximately 50%. 1, 2 For bilateral adrenal hyperplasia, lifelong medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment. 1, 2

Step 1: Confirm Diagnosis and Determine Laterality

Before initiating treatment, you must distinguish unilateral from bilateral disease, as this fundamentally determines whether the patient is a surgical candidate or requires lifelong medical therapy. 3, 2

Diagnostic Pathway:

• Screen using aldosterone-to-renin ratio (ARR ≥30 with plasma aldosterone ≥10-15 ng/dL) 1, 3
• Confirm with saline suppression test or oral sodium loading with 24-hour urine aldosterone 1, 3
• Localize with non-contrast CT scan of adrenal glands 3, 2
• Lateralize with adrenal venous sampling (AVS) before any surgical decision—this is mandatory except in patients <40 years with unilateral adenoma on imaging, as CT alone leads to unnecessary adrenalectomy in up to 25% of cases 3, 2, 4

Critical pitfall: Never proceed to surgery based on CT findings alone; AVS has 95% sensitivity and 100% specificity for distinguishing unilateral from bilateral disease. 3

Step 2: Treatment Algorithm Based on Subtype

For Unilateral Disease (Aldosterone-Producing Adenoma):

Laparoscopic unilateral adrenalectomy is the treatment of choice. 1, 2, 5

Outcomes:

• Blood pressure improvement: ~100% of patients 1, 2
• Complete hypertension cure: ~50% of patients 1, 2
• Normalizes hypokalemia, reduces antihypertensive medication requirements, and improves cardiac and kidney function 3

Important caveat: Even after successful surgery, some patients have residual hypertension due to irreversible vascular remodeling from delayed diagnosis—cure rates are higher with early diagnosis. 3, 2

For Bilateral Adrenal Hyperplasia:

Medical therapy with mineralocorticoid receptor antagonists is the definitive treatment. 1, 2, 6

First-Line: Spironolactone

• Starting dose: 12.5-25 mg daily 6
• Titration: Increase to 50-100 mg daily, up to maximum 300-400 mg daily if needed 3, 6
• Goal: Maintain high-normal serum potassium (4.0-5.0 mEq/L) without oral potassium supplements 3, 4

Monitoring schedule:

• Check potassium and creatinine at 3 days, 1 week, then monthly for first 3 months 2
• Subsequently every 3 months if stable 2

Alternative: Eplerenone (for patients with spironolactone side effects)

• Dose: 50-100 mg daily in 1-2 divided doses 2, 6
• Indication: Gynecomastia, breast tenderness, or sexual dysfunction on spironolactone 2
• Efficacy: Equal blood pressure control to spironolactone but less potent, requiring twice-daily dosing 3, 2

Add-On Therapy if Blood Pressure Not Controlled:

• Potassium-sparing diuretics (amiloride or triamterene) 6
• Calcium channel blockers 6
• Low-sodium diet 4

Step 3: Critical Safety Precautions with MRA Therapy

Before initiating any MRA:

• Verify serum potassium ≤5.0 mEq/L 2
• Confirm eGFR >30 mL/min or creatinine <2.0-2.5 mg/dL 2
• Discontinue all potassium supplements 2, 4

Absolute contraindications to combining MRAs with:

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

Use with extreme caution:

• eGFR <45 mL/min 2
• Concurrent use of multiple RAAS inhibitors 2

Special Consideration: Familial Hyperaldosteronism Type 1

Low-dose dexamethasone is the treatment for glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1), which is free of glucocorticoid effects and safe during pregnancy. 3, 2

Why Treatment Matters: Cardiovascular Risk Reduction

Primary aldosteronism carries dramatically higher cardiovascular risk than essential hypertension at equivalent blood pressure levels 3:

• 12.1-fold increase in atrial fibrillation 3
• 6.5-fold increase in myocardial infarction 3
• 4.2-fold increase in stroke 3
• 3.7-fold increase in heart failure 3

Targeted treatment—either surgical or medical—reverses aldosterone-mediated target-organ damage and mitigates this excess cardiovascular risk. 3

Common Pitfalls to Avoid

• Never rely on hypokalemia alone for diagnosis or screening—it is absent in ~50% of primary aldosteronism cases 1, 3, 2
• Never proceed to adrenalectomy without AVS (except in patients <40 years with clear unilateral adenoma) 3, 2
• Never underdose MRAs—titrate to maintain high-normal potassium without supplements 3, 4
• Never combine MRAs with potassium supplements or multiple RAAS inhibitors without intensive monitoring 2
• Delayed diagnosis leads to irreversible vascular remodeling—screen aggressively in resistant hypertension 3, 2

Referral Recommendation

All patients with confirmed primary aldosteronism should be referred to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 3