What is the diagnostic algorithm for primary aldosteronism patients?

Diagnostic Algorithm for Primary Aldosteronism

The diagnostic algorithm for primary aldosteronism begins with screening high-risk patients using the aldosterone-to-renin ratio (ARR), followed by confirmatory testing, and then subtype differentiation through adrenal venous sampling to determine appropriate treatment. 1, 2

Who to Screen

Screen patients with:

• Resistant hypertension (requiring 3+ medications)
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Adrenal incidentaloma with hypertension
• Early-onset hypertension (< 40 years)
• Family history of early-onset hypertension or cerebrovascular accident at young age
• First-degree relative with primary aldosteronism 1, 2

Screening Process

1. Aldosterone-to-Renin Ratio (ARR):

   • Most accurate and reliable screening test 1
   • Cutoff value: ≥30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h 1, 2
   • Plasma aldosterone should be at least 10 ng/dL (or 240 pmol/L) to interpret the test as positive 1, 3

2. Testing Conditions:

   • Morning measurement (preferably 8-10 AM)
   • Patient seated for 5-15 minutes
   • Unrestricted salt intake
   • Normal serum potassium levels
   • Withdraw interfering medications when possible:
     • Mineralocorticoid receptor antagonists (spironolactone, eplerenone): withdraw for at least 4 weeks
     • Beta-blockers, central alpha-2 agonists: can cause false positives
     • ACE inhibitors, ARBs: can cause false negatives 1, 2, 3

Confirmatory Testing

If ARR is elevated, proceed with one of these confirmatory tests:

• Intravenous saline suppression test: Infuse 2L of normal saline over 4 hours and measure aldosterone; failure to suppress aldosterone below 10 ng/dL confirms diagnosis
• Oral salt loading test: Measure 24-hour urinary aldosterone after salt loading; excretion >12-14 μg/24h confirms diagnosis
• Fludrocortisone suppression test: Administer fludrocortisone for 4 days; failure to suppress plasma aldosterone confirms diagnosis 1, 2

Subtype Differentiation

1. Imaging:

   • Non-contrast CT scan of adrenal glands as first-line imaging 2
   • MRI if CT is contraindicated or results are indeterminate

2. Adrenal Venous Sampling (AVS):

   • Gold standard for distinguishing unilateral from bilateral disease
   • Recommended before adrenalectomy, especially in:
     • Patients >40 years
     • Normal-appearing adrenals on imaging
     • Discordance between biochemical and imaging results 1, 2

Treatment Based on Subtype

1. Unilateral Disease (usually aldosterone-producing adenoma):

   • Laparoscopic adrenalectomy is first-line treatment
   • Improves BP in virtually 100% of patients
   • Complete cure of hypertension in approximately 50% 1, 2

2. Bilateral Disease (idiopathic hyperaldosteronism) or Patients Unsuitable for Surgery:

   • Mineralocorticoid receptor antagonists (spironolactone or eplerenone)
   • Starting dose: spironolactone 25-100 mg daily
   • Can titrate up to 400 mg daily as needed
   • Monitor for hyperkalemia, especially in patients with reduced renal function 1, 2

Common Pitfalls to Avoid

• Not screening high-risk patients: Primary aldosteronism affects 10-35% of hypertensive patients and up to 50% with resistant hypertension 2
• Assuming hypokalemia must be present: Only a minority of patients have hypokalemia at early stages 1, 2
• Relying solely on ARR without confirmatory testing: Can lead to false positives/negatives 2
• Proceeding to adrenalectomy without AVS: May lead to unnecessary surgery in 25% of patients 1

Follow-up and Monitoring

• Regular monitoring of blood pressure, serum potassium, and renal function
• For patients on mineralocorticoid receptor antagonists, monitor for hyperkalemia
• Assess for regression of target organ damage (left ventricular hypertrophy, etc.) 2

Early diagnosis and appropriate treatment significantly reduce cardiovascular and renal complications associated with primary aldosteronism, making this diagnostic algorithm essential for optimal patient outcomes 1, 2.