What is the approach to diagnose hyperaldosteronism?

Diagnostic Approach to Hyperaldosteronism

The diagnostic approach to hyperaldosteronism begins with screening using the aldosterone-to-renin ratio (ARR), which is currently the most accurate and reliable means of screening for primary aldosteronism. 1

Initial Screening

• 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 1
• Screening for primary aldosteronism is recommended in patients with:
  • Resistant hypertension 1
  • Hypertension with spontaneous or diuretic-induced hypokalemia 1
  • Hypertension with adrenal incidentaloma 1
  • Early-onset hypertension or history of cerebrovascular accident at a young age 1
  • Family history suggesting familial hyperaldosteronism 1, 2

Aldosterone-to-Renin Ratio (ARR) Testing

• The ARR has a high negative predictive value for screening of primary aldosteronism 1, 3
• An ARR >20 with serum aldosterone >16 ng/dL and plasma renin activity (PRA) <0.6 ng/mL per hour is suggestive of primary aldosteronism 1
• Some guidelines suggest an ARR >30 as the diagnostic threshold 2, 4
• For more severe cases, an ARR >50 has been shown to have 100% specificity and 92% sensitivity 4

Medication Considerations for ARR Testing

• Two approaches exist for ARR testing in patients already on antihypertensive medications 1:

  1. Test without changing medications and interpret results in context of current medications
  2. Discontinue interfering medications before testing when feasible

• Medications that can affect ARR interpretation include 1:

  • Mineralocorticoid receptor antagonists (raise aldosterone levels)
  • Beta-blockers and direct renin inhibitors (lower renin levels)
  • ACE inhibitors and ARBs (elevate renin levels)
  • Diuretics (affect both aldosterone and renin)

• Medications with minimal effect on ARR that can be continued 1:

  • Long-acting calcium channel blockers
  • Alpha-receptor antagonists

Confirmatory Testing

• After a positive ARR screening, confirmatory testing is required 3, 5
• Common confirmatory tests include:
  • Saline suppression test 2, 3
  • Salt loading test 2
  • Fludrocortisone suppression test 3

Subtype Differentiation

• Once primary aldosteronism is confirmed, determining whether it is unilateral or bilateral is crucial for treatment decisions 5, 6

• Imaging studies:

  • High-resolution CT or MRI of adrenal glands is indicated only after biochemical confirmation of primary aldosteronism 1
  • CT/MRI alone is insufficient for subtype differentiation as it may miss aldosterone-producing adenomas or show non-functioning nodules 3

• Adrenal vein sampling:

  • Currently the most reliable method to differentiate unilateral from bilateral disease 3, 5
  • Essential for patients >40 years with confirmed primary aldosteronism 2
  • Particularly important before considering surgical intervention 5

• Genetic testing:

  • Recommended for suspected familial hyperaldosteronism 7, 5
  • Particularly useful for detecting glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type I) 3

Pitfalls and Caveats

• False positive ARR results can occur with:

  • Low-renin states (volume expansion, dietary salt excess) 1
  • Certain medications (beta-blockers, central sympatholytics) 1
  • Advanced age 5

• False negative ARR results can occur with:

  • Concurrent use of mineralocorticoid receptor antagonists 1
  • Severe potassium depletion (suppresses aldosterone production) 6

• Interpretation of ARR should consider:

  • Sodium intake (preferably measured by 24-hour urinary sodium) 1
  • Time in menstrual cycle for females 1
  • Laboratory-specific reference ranges and units of measurement 1

By following this systematic approach to diagnosing hyperaldosteronism, clinicians can identify patients who would benefit from targeted treatment, potentially reducing cardiovascular morbidity and mortality associated with this condition 1, 5.