What lab tests are used to diagnose primary aldosteronism?

Laboratory Testing for Primary Aldosteronism

The plasma aldosterone-to-renin ratio (ARR) is the recommended initial screening test for primary aldosteronism, with additional confirmatory testing required for positive results. 1, 2

Initial Screening Test

• The plasma aldosterone-to-renin ratio (ARR) is the most accurate and reliable screening test for primary aldosteronism 1
• A positive ARR is typically defined as >20-30 when plasma aldosterone is measured in ng/dL and plasma renin activity in ng/mL/h 1
• For a valid positive result, plasma aldosterone concentration should be at least 10-15 ng/dL in addition to the elevated ratio 2, 3
• The specificity of the ratio improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2

Patient Preparation for Testing

• Patients should be potassium-replete before testing, as hypokalemia can suppress aldosterone production 2
• When clinically feasible, interfering medications should be discontinued 2, 3
• Beta-blockers, centrally acting drugs, and diuretics should ideally be stopped as they can affect results 2
• Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR 2
• If medications cannot be stopped, results should be interpreted in the context of the specific medications the patient is taking 2, 4

Proper Collection Technique

• Blood should be collected in the morning, with the patient out of bed for 2 hours prior to collection 2
• Patient should be seated for 5-15 minutes immediately before collection 2
• Blood should be drawn with the patient in a seated position 2

Confirmatory Testing

• A positive screening test requires confirmation with additional testing 2, 3
• Confirmatory tests include:
  • Oral sodium loading with 24-hour urine aldosterone measurement 2, 3
  • Intravenous saline suppression test 2, 3
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 2
• Mineralocorticoid receptor antagonists should be withdrawn at least 4 weeks before testing 2, 3

Subtype Determination

• After biochemical confirmation, imaging with non-contrast CT scan of the adrenal glands is recommended 2, 3
• Adrenal vein sampling is the gold standard for differentiating unilateral from bilateral disease, especially in patients >40 years 3
• This is crucial as approximately 50% of primary aldosteronism cases are unilateral and 50% are bilateral 3

Common Pitfalls to Avoid

• Not screening high-risk patients is a common pitfall, with only ~2-4% of eligible patients getting screened 2
• Relying solely on hypokalemia as a marker is problematic as it is absent in the majority of cases 1, 5
• Failing to refer patients with confirmed primary aldosteronism to specialists (hypertension specialist or endocrinologist) for further evaluation and treatment 1, 2

Who Should Be Screened

• Patients with resistant hypertension (BP not controlled on 3 medications including a diuretic) 1
• Patients with hypokalemia (spontaneous or substantial, if diuretic induced) 1
• Patients with incidentally discovered adrenal mass 1
• Patients with family history of early-onset hypertension 1
• Patients with stroke at a young age (<40 years) 1
• Patients with severe hypertension (BP >180/110 mmHg) 2

Primary aldosteronism is present in up to 20% of individuals with resistant hypertension, making appropriate laboratory testing essential for proper diagnosis and management 2, 5.