What is the management of an elevated aldosterone (Aldo)-to-renin ratio?

Management of an Elevated Aldosterone-to-Renin Ratio

An elevated aldosterone-to-renin ratio (ARR) requires confirmatory testing followed by subtype determination, with treatment consisting of either surgical intervention for unilateral disease or mineralocorticoid receptor antagonists for bilateral disease.

Initial Evaluation of Elevated ARR

• The ARR is the recommended screening test for primary aldosteronism, but requires careful interpretation as medications and other factors can influence results 1
• For a positive ARR test, plasma aldosterone concentration should be at least 10 ng/dL in addition to the elevated ratio 2
• False positive results can occur with low renin states even without truly elevated aldosterone levels 2

Confirmatory Testing

• Confirmatory testing is mandatory when an elevated ARR is detected, typically using:
  • Intravenous saline suppression test, or
  • Oral salt-loading test 2
• Testing should be performed with:
  • Unrestricted salt intake
  • Normal serum potassium levels
  • Withdrawal of mineralocorticoid receptor antagonists at least 4 weeks before testing 2

Medication Considerations Before Testing

Two approaches exist for patients already on antihypertensive medications:

1. Conduct ARR testing without changing medications:

   • Interpret results in context of specific medications the patient is taking
   • May require specialist input for interpretation 1

2. Discontinue interfering medications when feasible:

   • Beta-blockers, centrally acting drugs, and diuretics should be stopped
   • Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they don't interfere with ARR 1

Subtype Determination

• Adrenal imaging (CT, MRI) is the initial test to determine the subtype of primary aldosteronism 1, 3
• Adrenal venous sampling is recommended before surgical treatment to distinguish between unilateral and bilateral disease 3
• Without adrenal venous sampling, 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1

Treatment Options

For Unilateral Disease (Aldosterone-Producing Adenoma)

• Laparoscopic adrenalectomy is the treatment of choice 3
• Benefits include:
  • Improvement in blood pressure in nearly 100% of patients
  • Complete cure of hypertension in approximately 50% of cases 3
• Even patients with advanced hypertension can benefit from adrenalectomy 4

For Bilateral Disease (Idiopathic Hyperaldosteronism)

• Medical treatment with mineralocorticoid receptor antagonists is the mainstay of therapy 1, 3
• Spironolactone is the first-line treatment:
  • Starting dose of 25-100 mg daily 5
  • For primary hyperaldosteronism, doses of 100-400 mg daily may be needed 5
• Eplerenone is an alternative when spironolactone side effects (such as gynecomastia) occur:
  • Less potent at recommended doses than spironolactone 1
  • More selective binding to mineralocorticoid receptors 6

Monitoring and Follow-up

• Monitor serum potassium levels, as hyperkalemia is a potential complication of mineralocorticoid receptor antagonist therapy 5, 6
• In patients with renal impairment, careful monitoring of kidney function is essential as spironolactone may cause increased serum creatinine 4
• Treatment of primary aldosteronism can resolve hypokalemia, lower blood pressure, reduce antihypertensive medication requirements, and improve cardiac and kidney function 2

Important Clinical Pitfalls

• Not all patients with primary aldosteronism present with hypokalemia - it's absent in the majority of cases 2
• In patients with severe hypertension due to primary aldosteronism, plasma renin activity can escape suppression if hypertensive kidney damage develops 4
• The ARR may still be useful in these cases due to disproportionately high aldosterone levels 4
• Early specific treatment is indicated to prevent complications, even in patients with advanced hypertension 4