This episode describes the procedure and pitfalls of AVS (everyone’s favorite test)
Core AVS Indices and Interpretation
Adrenal venous sampling relies on three sequential biochemical indices to determine whether primary aldosteronism is unilateral or bilateral.
The first step calculates the Selectivity Index to confirm that the catheter tip was positioned correctly inside the adrenal lumen rather than a surrounding vessel. The index is determined by dividing the adrenal vein cortisol concentration by the peripheral vein cortisol concentration. Under unstimulated baseline conditions, a ratio greater than 2.0 verifies successful cannulation, whereas an ACTH-stimulated protocol requires a ratio greater than 5.0 due to increased cortical hormone output. If a sample fails to meet these specific thresholds, the blood is considered contaminated with peripheral circulation, rendering all subsequent calculations invalid and uninterpretable.
Once bilateral selectivity is confirmed, the Lateralization Index determines the source of aldosterone overproduction. The raw aldosterone concentration from each side is divided by its matching cortisol concentration to correct for asymmetrical blood flow and dilutional differences between the left and right adrenal veins. The final index is calculated by dividing the corrected ratio of the dominant high-secreting side by the corrected ratio of the non-dominant low-secreting side. An unstimulated ratio greater than 2.0 to 3.0 or an ACTH-stimulated ratio greater than 4.0 confirms unilateral disease, identifying the patient as a candidate for surgical adrenalectomy.
The Contralateral Suppression Index evaluates whether the unaffected, non-dominant gland is appropriately down-regulated by systemic feedback loops. It is calculated by dividing the corrected aldosterone-to-cortisol ratio of the non-dominant adrenal vein by the aldosterone-to-cortisol ratio of a peripheral vein. A ratio less than 1.0 confirms true physiological suppression, showing that the normal gland has gone dormant in response to the low-renin state caused by the contralateral tumor. If the index is 1.0 or greater, the non-dominant gland is actively manufacturing aldosterone independently, which strongly signals underlying bilateral hyperplasia despite a borderline lateralization index.
Autonomous cortisol secretion from an adrenal mass creates severe diagnostic pitfalls when evaluating primary aldosteronism via adrenal venous sampling. The excess cortisol triggers negative feedback on the hypothalamus and pituitary gland, downregulating adrenocorticotropic hormone (ACTH) secretion. Deprived of ACTH, the normal contralateral adrenal gland suppresses its own cortisol output. During an unstimulated procedure, this drop in cortisol falsely deflates the normal side's Selectivity Index, erroneously suggesting a catheter placement failure. Furthermore, using this artificially low cortisol level as a denominator falsely inflates the non-dominant side's corrected aldosterone ratio. This mathematical artifact can completely mask a true unilateral tumor or turn a bilateral hyperplasia case into a false unilateral diagnosis, risking an inappropriate or failed surgery.
Exogenous ACTH stimulation overcomes these pitfalls by directly binding to melanocortin 2 receptors on both glands. This pharmacological intervention overrides central pituitary suppression and forces the dormant, healthy gland to resume high-volume cortisol output, restoring a symmetrical biochemical baseline. However, ACTH can hyper-stimulate aldosterone secretion in adenomas that overexpress ACTH receptors, which alters standard lateralization index cutoffs. Measuring plasma free metanephrines provides an even better alternative for verifying selectivity because these medullary markers bypass the cortical steroid pathways entirely, remaining completely unaffected by cortisol autonomy or central pituitary feedback loops.
