What is the management approach for a patient with hyperaldosteronism and elevated plasma renin activity without hypertension?

Management of Hyperaldosteronism with Elevated Plasma Renin Activity Without Hypertension

For patients with hyperaldosteronism and elevated plasma renin activity without hypertension, mineralocorticoid receptor antagonist therapy with spironolactone is recommended as the first-line treatment, starting at 25-100 mg daily and titrating based on clinical response. 1, 2

Diagnostic Considerations

• This presentation represents an atypical form of primary aldosteronism, as classical primary aldosteronism typically presents with suppressed renin activity 3
• Elevated renin in the setting of hyperaldosteronism may indicate:
  • Secondary hypertensive kidney damage that has led to renin escape from suppression 2
  • Early-stage primary aldosteronism before hypertension develops 4
  • A forme fruste (incomplete expression) of primary aldosteronism 4

Confirmatory Testing

• Confirm the diagnosis with additional testing since the typical aldosterone-to-renin ratio (ARR) screening may be less reliable in this scenario 3, 5
• Recommended confirmatory tests include:
  • Oral salt-loading test with 24-hour urine aldosterone measurement 5
  • Intravenous saline suppression test to evaluate autonomous aldosterone production 3
• Ensure patient is potassium-replete before testing, as hypokalemia can suppress aldosterone production 5

Subtype Determination

• Once hyperaldosteronism is confirmed, determine if the source is unilateral or bilateral 5:
  • Initial imaging with non-contrast CT scan of the adrenal glands 5
  • Adrenal venous sampling is recommended if surgical intervention is being considered, as CT findings alone can be misleading in up to 25% of cases 5

Treatment Algorithm

1. Initial Medical Management:

   • Start spironolactone at 25-100 mg daily 1
   • Monitor serum potassium and renal function closely, as these patients may be sensitive to mineralocorticoid receptor antagonists 2
   • Titrate dose based on biochemical parameters and symptom control 1

2. For Unilateral Disease:

   • Consider laparoscopic adrenalectomy if confirmed by adrenal venous sampling 5
   • This approach can provide complete biochemical cure in most patients 5

3. For Bilateral Disease:

   • Continue long-term medical therapy with mineralocorticoid receptor antagonists 5
   • Spironolactone (100-400 mg daily) is the first-line agent 1
   • Eplerenone can be considered as an alternative if spironolactone side effects occur 5

Monitoring and Follow-up

• Regular monitoring of:
  • Blood pressure (even if initially normal, as hypertension may develop) 4
  • Serum potassium (risk of hyperkalemia with treatment) 2
  • Renal function (may worsen with treatment, especially in patients with pre-existing kidney damage) 2
  • Aldosterone levels to assess treatment efficacy 5

Special Considerations

• Even without hypertension, hyperaldosteronism can cause target organ damage including cardiac fibrosis and vascular remodeling 6
• Early treatment may prevent progression to hypertension and reduce cardiovascular complications 7
• The unusual combination of high aldosterone and high renin may indicate secondary kidney damage that requires careful monitoring during treatment 2

Pitfalls to Avoid

• Don't dismiss the diagnosis of primary aldosteronism due to the absence of hypertension - recent evidence shows it can be present in 11.3% of normotensive patients 4
• Don't rely solely on the aldosterone-to-renin ratio for diagnosis when renin is elevated 3
• Don't initiate high-dose spironolactone without close monitoring of potassium and renal function, as these patients may be particularly sensitive to mineralocorticoid receptor blockade 2
• Don't assume all cases require surgery - treatment should be guided by subtype determination and patient-specific factors 5