What is the significance of plasma renin activity (PRA) and serum aldosterone concentration in diagnosing and managing primary aldosteronism?

Plasma Renin Activity and Serum Aldosterone Concentration in Primary Aldosteronism

The aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism, with a positive result defined as ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10 ng/dL. 1

Who Should Be Screened

Screen for primary aldosteronism in hypertensive patients with any of the following: 1

• Resistant hypertension (uncontrolled on 3 medications including a diuretic) - affects up to 20% of these patients 2, 3
• Spontaneous or substantial diuretic-induced hypokalemia 1
• Incidentally discovered adrenal mass 1
• Family history of early-onset hypertension or stroke at age <40 years 1
• Severe hypertension (BP >180/110 mmHg) 3

Understanding the Pathophysiology

Primary aldosteronism involves autonomous aldosterone production that is independent of the renin-angiotensin system and cannot be suppressed with sodium loading. 2 This excess aldosterone causes: 1, 2

• Hypertension and cardiovascular damage
• Sodium retention with suppressed plasma renin activity
• Increased potassium excretion (though hypokalemia is absent in 50% of cases) 1, 2
• 12-fold increased risk of target organ damage including kidney injury compared to essential hypertension 2

Patient Preparation for Testing

Critical preparation steps to avoid false results: 3

• Ensure potassium repletion - hypokalemia suppresses aldosterone production 3
• Stop interfering medications when clinically feasible: 1, 3
  • Beta-blockers (cause false-positive ARR by suppressing renin) 4
  • Diuretics (suppress renin) 3
  • ACE inhibitors/ARBs (can cause false-negative results) 4
• Continue these medications if stopping is unsafe: 1, 3
  • Calcium channel blockers (minimal interference) 1
  • Alpha-receptor antagonists (minimal interference) 1
  • Doxazosin and fosinopril (do not interfere significantly) 4
• Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing 3

Blood Collection Technique

Proper timing and positioning are essential: 3

• Collect blood in the morning
• Patient should be out of bed for 2 hours prior to collection
• Patient should be seated for 5-15 minutes immediately before collection
• Ensure unrestricted salt intake and normal serum potassium levels 3

Interpreting the ARR

A positive screening test requires BOTH criteria: 1, 3

• ARR ≥30 (when aldosterone in ng/dL and renin activity in ng/mL/h)
• Plasma aldosterone concentration ≥10-15 ng/dL

The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1 Alternative cutoff values of ARR ≥100 provide highest specificity (99%) but lower sensitivity. 5

Critical Pitfalls to Avoid

Do not rely on hypokalemia as a screening trigger - it is absent in the majority of primary aldosteronism cases, yet significant organ damage still occurs. 1, 2, 3 This is one of the most common reasons for missed diagnoses.

Do not skip confirmatory testing - a positive ARR screening test requires confirmation with additional testing to demonstrate autonomous aldosterone secretion. 1, 3 Options include: 3

• Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress aldosterone below 5 ng/dL confirms diagnosis)
• Oral salt-loading test with 24-hour urine aldosterone measurement

Atypical Presentation: Elevated Renin with Hyperaldosteronism

If both aldosterone AND renin are elevated (not the typical suppressed renin pattern), this may represent: 6

• Early-stage primary aldosteronism before hypertension develops
• Forme fruste of primary aldosteronism
• Do not dismiss the diagnosis - proceed with confirmatory testing as the standard ARR may be less reliable in this scenario 6

Next Steps After Positive Screening

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination (unilateral vs. bilateral disease) and treatment planning. 1, 3 This typically involves: 2, 3

• Non-contrast CT scan of adrenal glands
• Adrenal venous sampling before offering adrenalectomy (CT findings alone can be misleading in up to 25% of cases) 2, 3

Treatment Implications

The distinction between unilateral and bilateral disease is critical for treatment: 2, 3

• Unilateral disease: Laparoscopic adrenalectomy improves blood pressure in virtually 100% of patients and achieves complete cure of hypertension in approximately 50% 2, 3
• Bilateral disease: Medical therapy with mineralocorticoid receptor antagonists (spironolactone first-line, eplerenone alternative) 2, 3

The deleterious effects of aldosterone overproduction are often reversible with appropriate treatment, reducing cardiovascular and renal damage. 2