What labs are recommended for diagnosing hypoaldosteronism?

Laboratory Diagnosis of Hypoaldosteronism

The diagnosis of hypoaldosteronism requires demonstrating low or inappropriately normal aldosterone levels in the setting of elevated plasma renin activity (PRA), combined with characteristic electrolyte abnormalities including hyperkalemia, hyponatremia, and metabolic acidosis. 1

Initial Laboratory Panel

Order the following tests simultaneously:

• Plasma aldosterone concentration (PAC) - typically low or inappropriately normal 2
• Plasma renin activity (PRA) - elevated in true hypoaldosteronism (distinguishes from primary aldosteronism where renin is suppressed) 1, 2
• Serum electrolytes - look for hyperkalemia (present in 94.6% of cases), hyponatremia (54.5% of cases), and metabolic acidosis (60.3% of cases) 2
• Serum bicarbonate - typically reduced due to impaired H+ excretion 2
• 24-hour urine sodium and potassium - demonstrates inappropriate sodium wasting with elevated urinary sodium despite hyponatremia 2

Key Diagnostic Ratios

The stimulated PAC/serum potassium ratio is particularly useful: all patients with isolated hypoaldosteronism have a ratio below 3, making this a reliable discriminatory test 3. This ratio should be calculated after stimulation with furosemide and ambulation, as stimulated aldosterone better reflects bioactivity on the collecting tubule than supine measurements 3.

Critical Timing and Collection Details

• Collect blood in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes immediately before collection 1
• Ensure unrestricted salt intake before testing, as sodium restriction can confound results 1
• Verify normal serum potassium if possible before testing, though this may not be feasible in hypoaldosteronism 1

Confirmatory Testing

If initial screening suggests hypoaldosteronism, perform stimulation testing:

• ACTH stimulation test using cosyntropin to assess adrenal cortical reserve and distinguish primary from secondary causes 4
• Measure aldosterone response to volume depletion (furosemide challenge) - failure to appropriately increase aldosterone confirms the diagnosis 3

Distinguishing Primary vs. Secondary Hypoaldosteronism

Primary adrenal insufficiency (Addison's disease):

• Low aldosterone AND low cortisol
• Requires 3-4 day course of Repository Corticotropin (40 USP units twice daily for 4 days) with retesting 4
• Little to no increase in plasma cortisol confirms primary disease 4

Isolated hypoaldosteronism:

• Low aldosterone with normal cortisol production
• 70% have subnormal baseline and stimulated PRA 3
• Only 5% have concurrent primary adrenal insufficiency 2

Genetic Testing Considerations

For congenital cases or young patients with unexplained hypoaldosteronism, consider molecular genetic testing:

• CYP11B2 gene sequencing for aldosterone synthase deficiency (CMO deficiency types I and II) 5, 6, 7
• NR3C2 gene sequencing for mineralocorticoid receptor defects (pseudohypoaldosteronism type I) 5, 6
• SCNN1A, SCNN1B, SCNN1G sequencing for epithelial sodium channel defects 5, 6

Critical Pitfalls to Avoid

High aldosterone levels in early infancy do not rule out aldosterone insufficiency - neonates may initially show elevated aldosterone that later normalizes or becomes low, potentially misleading diagnosis toward pseudohypoaldosteronism 5. Always interpret aldosterone levels in the context of renin activity and clinical presentation 5.

Normokalemia does not exclude hypoaldosteronism - 25% of patients with isolated hypoaldosteronism have normal potassium levels at presentation 3. The diagnosis should be considered in any patient with hypovolemic hyponatremia and urinary sodium wasting, even without hyperkalemia 2.

Hypovolemia significantly affects presentation - patients with volume depletion have more pronounced hyponatremia and a more florid clinical picture 2. Ensure adequate volume status assessment when interpreting laboratory results.

Medication Interference

Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing to avoid false results 1. Beta-blockers and diuretics should also be discontinued when clinically feasible, as they interfere with the renin-aldosterone axis 1.