How does ACE (Angiotensin-Converting Enzyme) inhibitor therapy affect the diagnosis of primary aldosteronism?

ACE Inhibitors and Primary Aldosteronism Diagnosis

If your patient is on ACE inhibitors, you can proceed with aldosterone-to-renin ratio (ARR) screening without stopping the medication, but you must interpret results knowing that ACE inhibitors increase renin and decrease aldosterone, which lowers the ARR and can cause false-negative results. 1, 2

Understanding the Drug Effect

ACE inhibitors interfere with ARR testing by:

• Increasing plasma renin activity significantly 3, 4
• Decreasing aldosterone levels to a minor extent 5
• Lowering the ARR, which can mask primary aldosteronism 2, 3

The net effect is that ACE inhibitors cause false-negative screening results in patients who actually have primary aldosteronism. 1, 2

Practical Management Options

Option 1: Test on Current Medications (Preferred for Safety)

Test while the patient continues ACE inhibitors and interpret results in the context of known drug effects. 1, 2

• If ARR is positive despite ACE inhibitor use (ARR ≥30 with aldosterone ≥10 ng/dL), this is highly specific for primary aldosteronism since the drug should have lowered the ratio 1
• If ARR is negative, you cannot rule out primary aldosteronism—the result may be falsely negative 2, 3
• This approach prioritizes patient safety by avoiding uncontrolled hypertension during medication withdrawal 2

Option 2: Switch to Non-Interfering Medications

Replace ACE inhibitors with calcium channel blockers (verapamil slow-release), alpha-blockers (doxazosin, prazosin), or hydralazine for 2-4 weeks before testing. 1, 4

• These medications minimally interfere with ARR and maintain blood pressure control 1, 4
• Calcium channel blockers have no significant influence on aldosterone or renin 5
• Doxazosin causes only -5% change in ARR compared to -30% with ACE inhibitors 4
• Do not use beta-blockers as substitutes—they suppress renin and cause false-positive results 1, 5

Option 3: Withdraw ACE Inhibitors (When Clinically Safe)

Stop ACE inhibitors for 2 weeks minimum before testing if blood pressure can be safely controlled with non-interfering agents. 1, 6

• Traditional guidelines recommend 4-6 weeks, but recent evidence shows 2 weeks is sufficient if renin suppression is confirmed 6
• Ensure adequate blood pressure control during withdrawal with alternative agents 1
• This approach provides the most accurate ARR results 2

Critical Pitfall to Avoid

Never rely on a negative ARR result in a patient taking ACE inhibitors to rule out primary aldosteronism. 2, 3

In one study, ACE inhibitor therapy caused false-negative results in 16-28% of patients with confirmed primary aldosteronism. 3 If clinical suspicion remains high (resistant hypertension, hypokalemia, adrenal mass), either switch medications and retest or proceed directly to confirmatory testing. 1

Alternative Diagnostic Approach

Research suggests the aldosterone/angiotensin II ratio may be superior to ARR in patients on ACE inhibitors, as it remains elevated in primary aldosteronism despite ACE inhibitor use. 3 However, this test requires specialized liquid chromatography-tandem mass spectrometry and is not widely available in clinical practice. 3

When Confirmatory Testing is Needed

If you proceed with screening on ACE inhibitors and get a positive result, withdraw ACE inhibitors for at least 2 weeks before confirmatory testing (saline suppression or oral sodium loading). 1, 6 Confirmatory tests require demonstration of autonomous aldosterone secretion that cannot be suppressed, and ACE inhibitors will interfere with this assessment. 1