What is the management approach for a patient with a high aldosterone renin ratio suggestive of primary aldosteronism?

Management of High Aldosterone-Renin Ratio Suggestive of Primary Aldosteronism

All patients with a positive aldosterone-renin ratio (ARR ≥30 with plasma aldosterone ≥10 ng/dL) require confirmatory testing to demonstrate autonomous aldosterone secretion, followed by subtype determination via imaging and adrenal venous sampling to guide definitive treatment—either laparoscopic adrenalectomy for unilateral disease or lifelong mineralocorticoid receptor antagonist therapy for bilateral disease. 1

Step 1: Confirm the Diagnosis with Suppression Testing

After a positive ARR screening test, you cannot proceed directly to treatment or imaging—confirmatory testing is mandatory because the ARR has limited specificity (67-99% depending on medications and population). 1

Confirmatory test options include: 1

• Oral sodium loading test: Administer high-sodium diet (>200 mEq/day) for 3 days, then collect 24-hour urine for aldosterone measurement. Failure to suppress urinary aldosterone below 12-14 mcg/24h confirms autonomous production. 1
• Intravenous saline suppression test: Infuse 2L normal saline over 4 hours. Plasma aldosterone >5 ng/dL post-infusion confirms the diagnosis. 1
• Fludrocortisone suppression test: Less commonly used but valid alternative. 1

Critical preparation requirements: 1

• Ensure unrestricted salt intake during testing
• Maintain normal serum potassium (hypokalemia suppresses aldosterone and causes false-negatives)
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before confirmatory testing 1

Step 2: Determine Unilateral vs. Bilateral Disease

This distinction is absolutely critical because it determines whether the patient undergoes surgery (curative for unilateral disease) or receives lifelong medical therapy (for bilateral disease). 1

Imaging first: 1

• Obtain non-contrast CT scan of adrenal glands to identify adenomas or hyperplasia
• Do NOT make treatment decisions based on CT alone—up to 25% of patients would undergo unnecessary adrenalectomy if CT findings were used without adrenal venous sampling 1

Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy 1, with one exception:

• Patients <40 years old with unilateral adenoma on CT can proceed directly to surgery, as bilateral hyperplasia is rare in this age group 1

Step 3: Definitive Treatment Based on Subtype

For Unilateral Disease (Aldosterone-Producing Adenoma):

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

Expected outcomes: 1

• Blood pressure improvement in virtually 100% of patients
• Complete cure of hypertension in approximately 50%
• Normalization of hypokalemia
• Reduced antihypertensive medication requirements
• Improved cardiac and kidney function parameters

Important caveat: Even after successful surgery, some patients have residual hypertension due to vascular remodeling from delayed diagnosis—cure rates are higher with early diagnosis. 1

For Bilateral Disease (Idiopathic Hyperaldosteronism):

Medical therapy with mineralocorticoid receptor antagonists is the cornerstone of lifelong treatment. 1, 2

First-line medication: 1, 2

• Spironolactone 100-400 mg daily for confirmed primary aldosteronism 2
• Start at lower doses (25-50 mg daily) if using as add-on therapy for resistant hypertension 1
• Titrate based on blood pressure response and potassium levels

Alternative option: 1

• Eplerenone: Less potent than spironolactone, requires twice-daily dosing, but has fewer anti-androgenic side effects (gynecomastia, sexual dysfunction)

Critical monitoring: 1

• Check serum potassium within 1 week of initiation and regularly thereafter
• Risk of hyperkalemia is significantly increased in patients with:
  • Chronic kidney disease
  • Diabetes
  • Concurrent use of ACE inhibitors, ARBs, or NSAIDs
  • Advanced age

Step 4: Immediate Management While Awaiting Confirmatory Testing

For patients with resistant hypertension and positive ARR, consider starting spironolactone 25-50 mg daily immediately, even before confirmatory testing is completed. 1

Rationale: 1

• Provides significant additional blood pressure reduction (25/12 mmHg) when added to multidrug regimens
• Benefits occur regardless of whether formal primary aldosteronism is ultimately confirmed
• Low doses minimize adverse effects while awaiting definitive diagnosis

Common Pitfalls to Avoid

Do not rely on hypokalemia as a screening trigger—it is absent in approximately 50% of primary aldosteronism cases. 1

Do not proceed to surgery based on CT findings alone—adrenal venous sampling is mandatory to prevent unnecessary adrenalectomy. 1

Do not perform confirmatory testing while patient is taking spironolactone—requires minimum 4-week washout period. 1

Do not skip confirmatory testing—the ARR alone has insufficient specificity to make treatment decisions. 1

Do not forget to correct hypokalemia before testing—it suppresses aldosterone production and causes false-negative results. 1

Referral Recommendations

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1 This is particularly important because:

• Adrenal venous sampling requires specialized expertise
• Interpretation of lateralization studies is complex
• Surgical candidacy assessment requires multidisciplinary input

Why This Matters: Cardiovascular Risk

Primary aldosteronism causes dramatically worse outcomes than essential hypertension at equivalent blood pressure levels: 1

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

This makes accurate diagnosis and appropriate treatment essential for reducing morbidity and mortality. 1