Adrenal Vein Sampling: Cortisol Ratios for Successful Cannulation and Lateralization
For successful cannulation during adrenal vein sampling (AVS), use a selectivity index (adrenal vein-to-peripheral vein cortisol ratio) of ≥2.75 to ≥5.0, with higher thresholds providing better diagnostic reproducibility; for lateralization, use a lateralization index (dominant-to-nondominant side aldosterone-to-cortisol ratio) of >3.5 to >4.0. 1, 2, 3
Cortisol Ratios for Successful Cannulation (Selectivity Index)
The selectivity index confirms proper catheter placement in the adrenal vein:
Minimum threshold: An adrenal vein-to-peripheral vein cortisol ratio ≥5.0 is the standard criterion for successful cannulation during ACTH-stimulated AVS 3
Optimal threshold for reproducibility: A cortisol ratio ≥2.75 is the minimum necessary to obtain consistent diagnoses between repeated AVS procedures, with higher ratios improving diagnostic accuracy 1
Impact of ACTH stimulation: ACTH increases cannulation success rates from 53% to 73%, particularly in centers with lower baseline expertise, though it may reduce lateralization rates 2
Alternative markers: An adrenal vein plasma metanephrine-to-peripheral vein ratio ≥12.0 or an adrenal vein metanephrine-to-normetanephrine ratio ≥2.0 can serve as alternatives to cortisol-based ratios, particularly when cortisol autonomy is suspected 4
Aldosterone-to-Cortisol Ratios for Lateralization (Lateralization Index)
The lateralization index determines whether aldosterone excess is unilateral or bilateral:
Standard threshold: A lateralization index (aldosterone-to-cortisol ratio from dominant side divided by nondominant side) >3.5 to >4.0 indicates unilateral aldosterone production amenable to surgical intervention 3, 4
With ACTH stimulation: When using ACTH, apply stricter criteria—a lateralization index >3 pre-ACTH combined with >2 post-ACTH predicts biochemical cure after unilateral adrenalectomy 2
Criteria stringency matters: Permissive criteria (lower thresholds) achieve only 35.3% diagnostic concordance between repeated procedures and should be avoided; stricter criteria improve reproducibility 1
Critical Pitfalls and Caveats
Concurrent autonomous cortisol secretion can confound AVS interpretation:
In patients with aldosterone-producing adenomas that also secrete cortisol autonomously, the cortisol ratio may falsely suggest failed cannulation on the contralateral side (by reducing cortisol levels) while reducing the aldosterone-to-cortisol ratio on the affected side 5
Always assess for autonomous cortisol production before AVS using 1 mg dexamethasone suppression testing; serum cortisol >50 nmol/L (>1.8 μg/dL) suggests autonomous secretion 6
Consider metanephrine-based ratios as an alternative when cortisol autonomy is confirmed, as these show strong agreement with cortisol-based measurements (sensitivity 98%, specificity 89%) 4
Intraprocedural cortisol measurement increases success:
Measuring cortisol immediately during the procedure allows for repeat sampling if bilateral selectivity is not achieved, increasing final success rates from 76% to 92% 3
If the first set of samples shows inadequate selectivity, obtain a second set during the same session rather than scheduling a repeat procedure 3
Clinical Context from Guidelines
AVS is the gold standard for distinguishing unilateral from bilateral aldosterone excess in primary aldosteronism:
Perform AVS in all surgical candidates with confirmed primary aldosteronism (plasma aldosterone-to-renin ratio >30 with aldosterone >10 ng/dL) to determine lateralization 6
Unilateral disease documented by AVS warrants laparoscopic adrenalectomy, which improves blood pressure in virtually 100% of patients and cures hypertension in approximately 50% 6
Bilateral disease or failed lateralization indicates medical management with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 6
For Cushing's disease evaluation using bilateral inferior petrosal sinus sampling (BIPSS):