How do you investigate for primary aldosteronism?

Investigation Protocol for Primary Aldosteronism

The investigation for primary aldosteronism should begin with plasma aldosterone-to-renin activity ratio (ARR) as the first-line screening test, followed by confirmatory testing and subtype evaluation to guide treatment decisions. 1

Who to Screen

Screen for primary aldosteronism in patients with:

• Resistant hypertension (poor control on ≥3 antihypertensive medications)
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Hypertension with adrenal incidentaloma
• Early-onset hypertension or family history of early-onset hypertension 1

Important: Do not rule out primary aldosteronism based on normal potassium levels, as hypokalemia is absent in the majority of cases (present in only 9-37% of patients) 1

Diagnostic Algorithm

Step 1: Screening with ARR

• Measure morning (preferably 8-10 AM) plasma aldosterone concentration (PAC) and plasma renin activity (PRA) 1, 2
• Positive ARR defined as ≥30 when PAC is reported in ng/dL and PRA in ng/mL/h, with PAC at least 10 ng/dL 1
• Optimal testing conditions:
  • Patient seated for 5-15 minutes
  • Normal potassium levels
  • Morning measurement 1

Clinical Pearl: ARR can be measured without discontinuing antihypertensive medications in most cases, which is more convenient and safer for patients 3. However, if possible, medications that significantly affect the ARR (such as spironolactone, eplerenone, and high-dose beta-blockers) should be withdrawn.

Step 2: Confirmatory Testing

If ARR is positive, confirm with one of these tests:

• Intravenous saline suppression test
• Oral salt loading test
• Fludrocortisone suppression test 1

These tests confirm autonomous aldosterone production that fails to suppress with volume expansion.

Step 3: Subtype Evaluation

Once primary aldosteronism is confirmed, determine the subtype:

1. Imaging:

   • Non-contrast CT scan of adrenal glands as first-line imaging
   • MRI as an alternative if CT is contraindicated or results are indeterminate 1

2. Adrenal Venous Sampling (AVS):

   • Gold standard for distinguishing between unilateral and bilateral aldosterone production
   • Recommended prior to adrenalectomy, particularly in:
     • Patients >40 years old
     • Normal-appearing adrenal glands on imaging
     • Discordance between biochemical and imaging results 1

Treatment Based on Subtype

• Unilateral disease (aldosterone-producing adenoma or unilateral hyperplasia):

  • Laparoscopic adrenalectomy is treatment of choice
  • Improves blood pressure in virtually 100% of patients
  • Achieves complete cure of hypertension in approximately 50% 1

• Bilateral disease (idiopathic bilateral hyperplasia):

  • Medical therapy with mineralocorticoid receptor antagonists (spironolactone or eplerenone)
  • Monitor for hyperkalemia, especially in patients with reduced renal function 1

Common Pitfalls to Avoid

1. Misinterpreting normal potassium: Primary aldosteronism is present in 5-13% of all hypertensive patients, but most are normokalemic 1, 4

2. Skipping confirmatory testing: A positive ARR alone is not diagnostic and must be followed by confirmation of autonomous aldosterone production 2

3. Relying solely on imaging: CT/MRI can miss small adenomas or show non-functioning incidentalomas; AVS is crucial for accurate subtype determination before surgery 1

4. Inadequate follow-up: After treatment initiation, regular monitoring of blood pressure, serum potassium, and renal function is essential 1

By following this systematic approach to investigating primary aldosteronism, clinicians can accurately diagnose this common but often overlooked cause of secondary hypertension, leading to appropriate treatment and reduction in cardiovascular morbidity and mortality.