What are the diagnostic tests and treatment options for primary aldosteronism?

Testing and Treatment for Primary Aldosteronism

The diagnostic approach for primary aldosteronism begins with screening using the plasma aldosterone-to-renin ratio (ARR) in high-risk patients, followed by confirmatory testing, and subtype determination through imaging and adrenal venous sampling to guide appropriate treatment with either surgery for unilateral disease or mineralocorticoid receptor antagonists for bilateral disease. 1, 2

Screening and Initial Evaluation

• Primary aldosteronism occurs in 5-10% of patients with hypertension and up to 20% of patients with resistant hypertension, making it one of the most common causes of secondary hypertension 2
• Screening is recommended for patients with:
  • Resistant hypertension (BP not controlled on 3 medications including a diuretic) 1, 2
  • Hypertension with spontaneous or diuretic-induced hypokalemia 2
  • Severe hypertension (BP >180/110 mmHg) 1
  • Adrenal incidentaloma 2
  • Early-onset hypertension or stroke at young age 2
  • Family history suggesting familial hyperaldosteronism 2

Diagnostic Testing

Patient Preparation

• Patients should be potassium-replete before testing, as hypokalemia can suppress aldosterone production 1
• Ideally, interfering medications should be discontinued when clinically appropriate:
  • Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible 1
  • Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR 1
  • Mineralocorticoid receptor antagonists (e.g., spironolactone) should be withdrawn at least 4 weeks before testing 3, 1

Initial Screening Test

• The aldosterone-to-renin ratio (ARR) is the recommended initial screening test 1, 2
• Blood should be collected in the morning, with the patient seated for 5-15 minutes immediately before collection 1
• A positive result is defined as:
  • ARR >30 (when plasma aldosterone is measured in ng/dL and plasma renin activity in ng/mL/h) 3, 2
  • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 3, 2
  • The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1

Confirmatory Testing

• A positive screening test requires confirmation with additional testing 1, 2
• Options include:
  • Intravenous saline suppression test 3
  • Oral salt-loading test with 24-hour urine aldosterone measurement 1
  • Testing should be performed with unrestricted salt intake and normal serum potassium levels 3, 1

Subtype Determination

• After biochemical confirmation, determine if the condition is unilateral or bilateral 1, 2
• Initial imaging with non-contrast CT scan of the adrenal glands 1
• Adrenal venous sampling is the gold standard for differentiating unilateral from bilateral disease 2
  • Should be performed by an experienced radiologist 2
  • Recommended prior to offering adrenalectomy, as up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1

Treatment

For Unilateral Disease

• Laparoscopic unilateral adrenalectomy is the treatment of choice 3, 1, 2
• Improves blood pressure in virtually 100% of patients and results in complete cure of hypertension in approximately 50% 3, 2
• Resolves hypokalemia, reduces the number of antihypertensive medications required, and improves parameters of impaired cardiac and kidney function 3

For Bilateral Disease

• Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment 3, 2
• Spironolactone is the first-line treatment 2
  • Dosage: 100 mg to 400 mg daily for primary hyperaldosteronism 4
  • Can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient 4
• Eplerenone is an alternative option with fewer anti-androgenic side effects 3

Monitoring and Follow-up

• Close monitoring of electrolytes and renal function is essential when initiating treatment with MRAs 2
• Avoid combining MRAs with other potassium-sparing medications or potassium supplements due to risk of hyperkalemia 2
• Use MRAs with caution in patients with significant renal dysfunction (eGFR <45 mL/min) 2

Common Pitfalls to Avoid

• Not screening high-risk patients is a common pitfall, with only ~2-4% of eligible patients getting screened 1
• Relying solely on hypokalemia as a marker, as it is absent in the majority of cases 1, 5
• Failing to withdraw interfering medications before testing 1
• Not referring patients with confirmed primary aldosteronism to specialists with expertise in management 1