What are the laboratory findings in hyperaldosteronism?

Laboratory Findings in Hyperaldosteronism

The key laboratory findings in hyperaldosteronism are elevated plasma aldosterone concentration (≥10-15 ng/dL), suppressed plasma renin activity, and an aldosterone-to-renin ratio (ARR) >30, with hypokalemia present in only approximately 50% of cases. 1, 2

Primary Screening Tests

Aldosterone-to-Renin Ratio (ARR)

• The ARR is the recommended initial screening test, calculated by dividing plasma aldosterone concentration (ng/dL) by plasma renin activity (ng/mL/h) 2
• A positive screening result is defined as ARR ≥30 with plasma aldosterone concentration ≥10 ng/dL 2, 3
• The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2

Plasma Aldosterone and Renin

• Elevated plasma aldosterone levels (>16 ng/dL) with suppressed plasma renin activity (<0.5 ng/mL/h) are the hallmark findings 1, 4
• Blood should be drawn in the morning with the patient seated for 5-15 minutes after being out of bed for 2 hours 2

Electrolyte Abnormalities

Potassium Levels

• Hypokalemia is present in only 50% of patients with primary aldosteronism - normal potassium does not exclude the diagnosis 1, 5, 4
• When present, hypokalemia results from excessive aldosterone-induced potassium excretion in the distal renal tubule 1
• Relying solely on hypokalemia as a screening marker will miss the majority of cases 2, 5

Sodium and Volume Status

• Sodium retention occurs due to aldosterone's action on the distal convoluted tubule, leading to mild extracellular volume expansion 1
• This volume expansion is what normally suppresses renin in primary aldosteronism 6

Confirmatory Testing

Saline Suppression Test

• After a positive ARR, confirmatory testing is mandatory to demonstrate autonomous aldosterone secretion 1, 2
• The intravenous saline suppression test involves infusing 2L of normal saline over 4 hours 1, 7
• Failure to suppress plasma aldosterone below 5 ng/dL after saline loading confirms the diagnosis 1, 2

Oral Sodium Loading Test

• An alternative confirmatory test involves oral salt loading with measurement of 24-hour urine aldosterone 1, 2
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 2

Fludrocortisone Suppression Test

• This test can confirm primary hyperaldosteronism when failure to reduce plasma aldosterone below threshold occurs after fludrocortisone administration 2, 4

Important Pre-Test Considerations

Patient Preparation

• Patients must be potassium-replete before testing, as hypokalemia can suppress aldosterone production and cause false-negative results 2
• Interfering medications should be discontinued when clinically appropriate 2

Medication Adjustments

• Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible 2
• Long-acting calcium channel blockers and alpha-receptor antagonists minimally interfere with ARR and can be used as alternatives 2
• If medications cannot be stopped, interpret results in the context of the specific medications being taken 2

Additional Laboratory Findings

Renal Function

• Serum creatinine may be elevated, particularly in patients with severe hypertension and secondary kidney damage 1, 6
• In patients with renal impairment, the risk of hyperkalemia increases significantly when treated with mineralocorticoid receptor antagonists 8, 9

Urinary Potassium

• Inappropriate kaliuresis (elevated urinary potassium excretion) in the setting of hypokalemia suggests renal potassium wasting from aldosterone excess 10

Common Pitfalls to Avoid

• Do not exclude primary aldosteronism based on normal potassium levels alone - normokalemic hyperaldosteronism is common 4, 7
• Do not rely on a single ARR measurement - the diagnosis should be confirmed with at least two measurements showing elevated aldosterone and suppressed renin 4
• In patients with severe hypertension and secondary kidney damage, plasma renin activity may escape suppression, but the ARR will still be elevated due to disproportionately high aldosterone levels 6
• Normal aldosterone levels in basal conditions do not exclude hyperaldosteronism - dynamic testing may be required 7