What is the initial screening test for primary aldosteronism?

Screening for Primary Aldosteronism

The plasma aldosterone-to-renin ratio (ARR) is the recommended initial screening test for primary aldosteronism. 1

Who Should Be Screened

Screen hypertensive patients with any of the following high-risk features: 1

• Resistant hypertension (blood pressure uncontrolled on 3 medications including a diuretic) 1, 2
• Spontaneous or diuretic-induced hypokalemia (though most patients with primary aldosteronism are normokalemic) 1
• Incidentally discovered adrenal mass on imaging 1
• Family history of early-onset hypertension or stroke before age 40 1
• Severe hypertension (>180/110 mmHg) 2

Primary aldosteronism occurs in 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension, yet only 2-4% of eligible patients are actually screened—a critical missed opportunity. 1, 2, 3

Patient Preparation Before Testing

Proper preparation is essential to avoid false results: 2

• Correct hypokalemia first, as low potassium suppresses aldosterone production and causes false-negative results 2, 4
• Ensure unrestricted salt intake before testing 1, 2
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks 1, 2
• Stop interfering medications when clinically feasible: 2, 4
  • Beta-blockers, centrally acting drugs, and diuretics should be discontinued
  • Substitute with long-acting calcium channel blockers or alpha-receptor antagonists, which minimally interfere with ARR
  • ACE inhibitors and ARBs can cause false-negative results by stimulating renin 4, 5

If medications cannot be stopped, interpret results in the context of the specific drugs the patient is taking. 2

Blood Collection Technique

Standardized collection improves test accuracy: 2

• Draw blood in the morning 2
• Patient should be out of bed for 2 hours prior to collection 2
• Patient should be seated for 5-15 minutes immediately before blood draw 2

Interpreting the ARR

A positive screening test requires BOTH criteria: 1, 2

• ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) 1
• Plasma aldosterone concentration ≥10 ng/dL (some sources suggest ≥15 ng/dL) 1, 2

The aldosterone threshold is critical because very low renin levels alone can artificially elevate the ratio. 1 Some experts recommend using a minimum plasma renin activity of 0.5 ng/mL/h in calculations to improve specificity. 2

Important caveat: The ARR has excellent specificity (>90%) but variable sensitivity depending on medication use. 2, 5 One study found sensitivity as low as 22% under random medication, improving significantly when interfering drugs were stopped. 5 The test also has poor reproducibility, with nearly five-fold differences in values taken under identical conditions. 5

Next Steps After Positive Screening

A positive ARR is only a screening test—confirmatory testing is mandatory: 1, 2, 3

• Confirmatory tests include: 1, 2

  • Intravenous saline suppression test
  • Oral sodium loading with 24-hour urine aldosterone measurement
  • Fludrocortisone suppression test

• After biochemical confirmation, refer to a hypertension specialist or endocrinologist for subtype determination 1, 2

• Subtype evaluation requires: 2, 3

  • Non-contrast CT scan of adrenal glands
  • Adrenal venous sampling (AVS) before offering surgery, as CT findings alone are misleading in up to 25% of cases 2

Treatment Implications

The distinction between unilateral and bilateral disease determines treatment: 2, 3

• Unilateral disease (aldosterone-producing adenoma): Laparoscopic adrenalectomy improves blood pressure in virtually 100% and cures hypertension in approximately 50% 1, 2
• Bilateral disease (idiopathic hyperplasia): Medical therapy with mineralocorticoid receptor antagonists (spironolactone first-line, eplerenone alternative) 2, 3

Common Pitfalls to Avoid

• Don't rely on hypokalemia as a marker—it's absent in the majority of primary aldosteronism cases 1
• Don't skip confirmatory testing after a positive ARR, as false positives occur 2, 5
• Don't base surgical decisions on CT imaging alone—adrenal venous sampling is essential 2
• Don't dismiss the diagnosis in normotensive patients—primary aldosteronism can occur in 11.3% of normotensive individuals 6

The toxic effects of aldosterone cause 3.7-fold increased heart failure, 4.2-fold increased stroke, 6.5-fold increased MI, and 12.1-fold increased atrial fibrillation compared to matched essential hypertension—making early detection and treatment critical for reducing morbidity and mortality. 1