Aldosterone-to-Cortisol Ratio Interpretation in Adrenal Vein Sampling
The interpretation of aldosterone-to-cortisol ratios in adrenal vein sampling depends critically on whether cosyntropin stimulation is used, with different cutoff values for lateralization: >4:1 with cosyntropin stimulation indicates unilateral disease, while >2:1 without cosyntropin suggests unilateral disease.
Protocol-Dependent Interpretation
The aldosterone-to-cortisol ratio thresholds vary based on your AVS protocol 1:
With Continuous Cosyntropin Stimulation
- Lateralization index (high-side to low-side) >4:1 = unilateral aldosterone excess
- Lateralization index <3:1 = bilateral aldosterone hypersecretion
- Lateralization index 3:1-4:1 = indeterminate (may be either unilateral or bilateral disease)
These cutoffs achieve 95% sensitivity and 100% specificity for detecting unilateral aldosterone hypersecretion 1.
Without Cosyntropin Stimulation
- Lateralization index >2:1 = consistent with unilateral disease 1
- Some centers use an alternative approach: comparing adrenal vein aldosterone-cortisol ratios to peripheral vein samples
Alternative Peripheral Comparison Method
When comparing to peripheral venous samples 1:
- Adrenal vein A/C ratio ≥2.5 times peripheral on one side, AND
- Contralateral adrenal vein A/C ratio no higher than peripheral (indicating contralateral suppression)
- This pattern indicates lateralization and suggests unilateral adrenalectomy will improve outcomes
Confirming Successful Sampling (Selectivity Index)
Before interpreting lateralization ratios, you must confirm adequate adrenal vein catheterization 2:
- With cosyntropin: adrenal vein-to-IVC cortisol ratio >5:1
- Without cosyntropin: adrenal vein-to-IVC cortisol ratio >1.4-3.0
Critical Caveats
The "gray zone" (3:1-4:1 with cosyntropin) requires cautious interpretation 1. These patients may have either unilateral or bilateral disease. You must integrate:
- Clinical presentation
- CT/MRI findings
- Contralateral suppression data
- Consider repeat AVS if surgical decision remains unclear
Cosyntropin controversy: While cosyntropin improves selectivity indices and reduces technical failures 3, it may cause discordance in lateralization interpretation. Studies show 19% discordance rates between pre- and post-cosyntropin results, with 64% of discordant cases showing apparent unilateral disease becoming bilateral after cosyntropin 2. However, most studies find no difference in post-adrenalectomy outcomes regardless of cosyntropin use 2.
French consensus recommends a lateralization cutoff of ≥4:1 for simultaneous bilateral sampling without ACTH stimulation 4, emphasizing the importance of institutional protocols.
Practical Algorithm
- Verify selectivity first - ensure adequate catheterization using cortisol gradients
- Calculate cortisol-corrected aldosterone ratios for both adrenal veins
- Apply protocol-specific cutoffs:
- Cosyntropin protocol: >4:1 = unilateral; <3:1 = bilateral
- Non-stimulated protocol: >2:1 = unilateral
- For indeterminate results (3:1-4:1): assess contralateral suppression and correlate with imaging
- Consider repeat AVS if results don't align with clinical picture or imaging 5, 6
The most recent 2025 Endocrine Society guideline 2 maintains these established cutoffs while emphasizing that institutions should develop expertise with their chosen protocol rather than switching between methods.