What is the appropriate management for an adult patient with a high aldosterone/renin (A/R) ratio, suspected primary aldosteronism, hypertension, and hypokalemia?

Management of High Aldosterone/Renin Ratio with Suspected Primary Aldosteronism

For an adult with elevated aldosterone/renin ratio, hypertension, and hypokalemia, you must first confirm autonomous aldosterone secretion with a suppression test, then determine laterality with adrenal venous sampling before proceeding to either unilateral laparoscopic adrenalectomy (for unilateral disease) or lifelong mineralocorticoid receptor antagonist therapy with spironolactone (for bilateral disease). 1, 2

Step 1: Confirm the Diagnosis with Suppression Testing

Your positive screening ARR requires mandatory confirmatory testing to demonstrate autonomous aldosterone production that cannot be suppressed. 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 the diagnosis 2
• Oral sodium loading test: Liberal salt intake with 24-hour urine aldosterone measurement 1, 2

Critical preparation requirements:

• Ensure serum potassium is normal (4.0-5.0 mEq/L) before testing, as hypokalemia suppresses aldosterone production and causes false-negatives 2, 3
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing 2
• Maintain unrestricted salt intake during the testing period 1, 2

Step 2: Determine Unilateral vs. Bilateral Disease

This distinction is mandatory because it determines surgical candidacy versus lifelong medical therapy. 2

Imaging first:

• Obtain non-contrast CT scan of adrenal glands as initial subtype evaluation 2

Adrenal venous sampling (AVS) is mandatory before surgery:

• AVS is required in all patients being considered for adrenalectomy to distinguish unilateral from bilateral aldosterone production 2
• Do not proceed to surgery based on CT findings alone—up to 25% of patients would undergo unnecessary adrenalectomy without AVS, as CT adenomas can represent bilateral hyperplasia 2
• Exception: AVS may be omitted only in patients <40 years old with imaging showing a single affected gland, as bilateral hyperplasia is rare in this age group 2

Step 3: Treatment Based on Subtype

For Unilateral Disease (Adenoma or Unilateral Hyperplasia):

Laparoscopic unilateral adrenalectomy is the treatment of choice. 2, 4

• Improves blood pressure in virtually 100% of patients 2
• Achieves complete cure of hypertension in approximately 50% of cases 2, 4
• Normalizes hypokalemia and reduces antihypertensive medication requirements 2
• Improves cardiac and kidney function parameters 2, 4

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

For Bilateral Disease (Bilateral Adrenal Hyperplasia):

Medical therapy with mineralocorticoid receptor antagonists is the cornerstone of lifelong treatment. 2, 3

Spironolactone dosing (first-line): 2, 3

• Start 50-100 mg once daily 2
• Titrate up to 300-400 mg once daily if necessary 2
• FDA-approved dosing for primary hyperaldosteronism: 100-400 mg daily 3
• Can be taken with or without food, but establish a consistent pattern 3

Eplerenone (alternative):

• Less potent than spironolactone and requires twice-daily dosing 2
• Fewer anti-androgenic side effects (less gynecomastia, breast tenderness) 2

Critical Monitoring and Safety Considerations

Monitor for hyperkalemia and renal function deterioration: 5

• Patients with severe hypertension and renal damage may respond to spironolactone with marked increases in serum creatinine and potassium 5
• This occurs due to decreased filtered sodium load and spironolactone-induced reduction in mineralocorticoid function 5
• Risk is highest in patients with baseline renal impairment (elevated creatinine) 5

Avoid concomitant potassium-raising agents: 3

• Do not combine with potassium supplementation, salt substitutes containing potassium, ACE inhibitors, ARBs, NSAIDs, or heparin without close monitoring 3
• These combinations can lead to severe hyperkalemia 3

Common Diagnostic Pitfalls to Avoid

Do not rely on hypokalemia as a screening trigger: Only 50% of primary aldosteronism patients have hypokalemia—normal potassium does not exclude the diagnosis. 2, 6

Do not skip confirmatory testing: A positive ARR alone is insufficient due to variable sensitivity (22-66%) and specificity (67-99%) depending on medications and population. 2

Do not proceed to surgery without AVS: CT findings alone are unreliable for determining laterality. 2

Recognize that severe hypertension with renal damage can cause PRA to escape suppression: In patients with hypertensive kidney damage, PRA may be normal or high-normal despite primary aldosteronism, but the ARR remains elevated due to disproportionately high aldosterone. 5

Why Early Treatment Matters

Primary aldosteronism causes target organ damage beyond what blood pressure elevation alone would cause, including 12-fold increased risk of kidney injury, widespread tissue fibrosis, and increased cardiovascular events. 4, 7 These toxic effects of aldosterone are often reversible with appropriate treatment (surgery or mineralocorticoid receptor antagonists). 2, 4