Diagnostic Criteria of Primary Aldosteronism
Primary aldosteronism should be diagnosed through a stepwise approach including screening with aldosterone-to-renin ratio (ARR), confirmatory testing, and subtype differentiation, with ARR ≥30 (when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h) and plasma aldosterone at least 10 ng/dL considered positive. 1
Who Should Be Screened
Screening is recommended for high-risk patients including:
- Patients with resistant hypertension
- Hypertension with spontaneous or diuretic-induced hypokalemia
- Patients with adrenal incidentaloma and hypertension
- Early-onset hypertension
- Family history of early-onset hypertension or cerebrovascular accident at a young age 1
Screening Process
Step 1: Aldosterone-to-Renin Ratio (ARR) Testing
- ARR is the most reliable first-line screening test 1
- Testing conditions:
- Morning measurement (preferably between 8-10 AM)
- Patient seated for 5-15 minutes
- Unrestricted salt intake
- Normal serum potassium levels
- Withdrawal of interfering medications when possible 1
Important note: Medications that can affect ARR interpretation include mineralocorticoid receptor antagonists, direct renin inhibitors, and β-blockers. These should be considered when interpreting results 1.
Positive screening criteria:
- ARR ≥30 (when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h)
- Plasma aldosterone concentration ≥10 ng/dL (240 pmol/L) 1
Step 2: Confirmatory Testing
A positive ARR alone is not diagnostic and requires confirmation with one of these tests:
- Intravenous saline suppression test
- Oral salt loading test
- Fludrocortisone suppression test (failure of 4-day administration to reduce plasma aldosterone below threshold value) 2, 1
Subtype Differentiation
After confirming primary aldosteronism, determining the subtype is crucial for treatment decisions:
Imaging
- Non-contrast CT scan of adrenal glands is first-line imaging
- MRI is an alternative if CT is contraindicated 1
Adrenal Venous Sampling (AVS)
- Gold standard for distinguishing between unilateral and bilateral aldosterone production
- Recommended prior to adrenalectomy, particularly in:
- Patients >40 years
- Normal-appearing adrenal glands on imaging
- Discordance between biochemical and imaging results 1
Common Pitfalls and Caveats
Relying solely on hypokalemia: Only a small number of patients have hypokalemia at early stages 2. Most patients with primary aldosteronism are normokalemic 3.
Skipping confirmatory testing: Relying solely on ARR without confirmatory testing can lead to false positives and false negatives 1.
Imaging limitations: Adenomas on CT or MRI can turn out to be hyperplasia. False positives are common because nodular hyperplasia can occur even with functioning adenomas, and observed adenomas may be non-functioning 2. Without AVS, up to 25% of patients could undergo unnecessary adrenalectomy 2.
Underdiagnosis: Primary aldosteronism affects 5-13% of all hypertensive patients and up to 50% of patients with resistant hypertension, yet fewer than 1% are diagnosed and treated 1, 4.
Treatment Based on Subtype
Unilateral disease (usually aldosterone-producing adenoma): Laparoscopic adrenalectomy, which improves blood pressure in virtually 100% of patients and achieves complete cure of hypertension in approximately 50% 1
Bilateral disease (idiopathic hyperaldosteronism): Mineralocorticoid receptor antagonists (e.g., spironolactone starting at 25-100 mg daily, titrating up to 400 mg daily as needed) 1
Primary aldosteronism is associated with increased cardiovascular risk independent of blood pressure levels, making accurate diagnosis and appropriate treatment essential for reducing associated morbidity and mortality 1.