Is an aldosterone-to-renin ratio (ARR) of 52 diagnostic of primary aldosteronism?

Aldosterone-to-Renin Ratio of 52 is Not Diagnostic of Primary Aldosteronism Without Confirmatory Testing

An aldosterone-to-renin ratio (ARR) of 52 alone is suggestive of primary aldosteronism but is not diagnostic without additional confirmatory testing. 1

Understanding ARR as a Screening Tool

The ARR is widely recommended as the initial screening test for primary aldosteronism, but several important considerations must be kept in mind:

ARR Interpretation Requirements:

• A high ARR (>20-30) is considered a positive screening result 1, 2
• For proper interpretation, serum aldosterone should be >15-16 ng/dL 1, 2
• The specificity of ARR is low due to common low-renin states (e.g., volume expansion, dietary salt excess) 1

Factors Affecting ARR Accuracy:

• Medications significantly impact results:
  • Mineralocorticoid receptor antagonists raise aldosterone levels 1
  • Direct renin inhibitors and β-blockers lower renin levels 1, 3
  • ACE inhibitors and ARBs elevate renin (increasing test sensitivity) 1, 2
• Uncorrected hypokalemia can lead to false negatives 3
• Gender differences exist (females have higher ratios) 3
• Age and renal dysfunction can cause false positives 3

Why Confirmatory Testing is Essential

Despite a positive ARR screening result (>20-30), confirmatory testing is mandatory because:

1. ARR performance varies widely with sensitivity ranging from 10% to 100% and specificity from 70% to 100% 4
2. In some studies, ARR sensitivity was <50%, showing limited ability to identify primary aldosteronism 4
3. In 36% of cases with elevated ARR, the ratio merely reflected low renin without increased aldosterone 5
4. Cases exist where primary aldosteronism occurs despite negative ARR 6

Recommended Diagnostic Algorithm

1. Initial Screening: ARR >20 when serum aldosterone is >16 ng/dL and PRA is <0.6 ng/mL per hour is suggestive of primary aldosteronism 1

2. Medication Adjustment: If possible, discontinue interfering medications before testing:

   • Stop diuretics for 6 weeks
   • Stop other interfering medications for 2 weeks
   • Substitute with non-interfering agents like verapamil, hydralazine, prazosin, or doxazosin 3

3. Confirmatory Testing (one of the following):

   • Intravenous saline suppression test
   • Oral salt-loading test with 24-hour urine aldosterone
   • Fludrocortisone suppression test 2

4. Imaging: If confirmed, proceed with adrenal imaging (CT or MRI) 2

5. Adrenal Vein Sampling: Consider for patients >40 years, normal-appearing adrenal glands, or discordance between biochemical and imaging results 2

Clinical Implications

Primary aldosteronism is more prevalent than previously thought (10-35% of all hypertensive patients and up to 50% of patients with resistant hypertension) 1. It's associated with increased cardiovascular risk independent of blood pressure levels 1.

Common pitfalls to avoid:

• Relying solely on ARR without confirmatory testing
• Failing to screen high-risk patients (resistant hypertension, hypokalemia, adrenal incidentaloma)
• Not accounting for medications that affect ARR interpretation
• Assuming primary aldosteronism doesn't occur without hypokalemia (it frequently does) 1

In conclusion, while an ARR of 52 is certainly suspicious for primary aldosteronism, definitive diagnosis requires confirmatory testing to avoid both false positives and false negatives that can occur with ARR screening alone.