When is Adrenal Venous Sampling (AVS) useful in a Cushing's syndrome case?

When is Adrenal Venous Sampling (AVS) Useful in Cushing's Syndrome?

AVS is useful in Cushing's syndrome when patients have bilateral adrenal masses or morphologically normal adrenal glands on imaging, as it can distinguish unilateral from bilateral cortisol production and prevent unnecessary bilateral adrenalectomy or guide appropriate surgical planning. 1, 2

Primary Indication: Bilateral Adrenal Abnormalities

AVS should be performed in ACTH-independent Cushing's syndrome when:

• Bilateral adrenal masses or nodules are present on CT imaging 1, 2, 3
• Morphologically normal adrenal glands are seen despite biochemical evidence of autonomous cortisol secretion 1
• Imaging findings are indeterminate or discordant with clinical presentation 2

The rationale is that CT imaging alone is unreliable for determining laterality of cortisol production, with AVS results being discordant with imaging in up to 50% of cases in some series 2.

Technical Interpretation Criteria

A lateralization index (cortisol/reference hormone ratio) ≥2 between adrenal veins indicates unilateral dominant cortisol production 1, 2. This threshold helps distinguish:

• Unilateral cortisol-secreting adenoma → candidate for unilateral adrenalectomy 1, 2
• Bilateral cortisol hypersecretion → requires bilateral adrenalectomy or medical management 1, 3
• Dominant gland in bilateral disease → may allow staged unilateral adrenalectomy first 2

Cortisol measurement in catheterization samples confirms proper catheter placement, with adrenal vein samples showing significantly higher cortisol levels than peripheral samples 4.

Clinical Impact on Management Decisions

AVS definitively changes management in a substantial proportion of cases:

• Prevented inappropriate bilateral adrenalectomy in patients with unilateral disease despite bilateral imaging abnormalities 1, 5
• Avoided unnecessary surgery by confirming bilateral disease requiring medical management instead 2
• Helped 2 out of 10 patients in one series avoid chronic steroidogenesis inhibitors or inappropriate bilateral adrenalectomy 1
• Changed treatment from surgery to medical management in select cases 2

Important Caveats and Limitations

AVS is NOT routinely recommended for all Cushing's syndrome cases 2. It is specifically reserved for:

• Cases where imaging shows bilateral abnormalities or is normal 1, 3, 6
• Situations where distinguishing unilateral from bilateral disease will change surgical approach 2, 5

Common pitfalls to avoid:

• In bilateral disease, adrenal mass size often influences surgical decision-making more than AVS results, so clinical judgment remains essential 3
• AVS requires technical expertise and successful catheterization (success rate approximately 80-90% in experienced centers) 3
• Dexamethasone suppression should be used during the procedure to optimize interpretation 3

Pre-AVS Evaluation Required

Before proceeding with AVS, confirm:

• ACTH-independent hypercortisolism with suppressed ACTH levels 5, 6
• Autonomous cortisol secretion using 1 mg dexamethasone suppression test, with serum cortisol >50 nmol/L (>1.8 μg/dL) 7, 8
• Exclusion of pheochromocytoma with plasma or 24-hour urinary metanephrines 9

Post-AVS Management Algorithm

Based on AVS lateralization results:

• Unilateral dominant production (lateralization index ≥2): Proceed with unilateral laparoscopic adrenalectomy 1, 2
• Bilateral cortisol hypersecretion: Consider bilateral adrenalectomy or medical management with steroidogenesis inhibitors (ketoconazole 400-1200 mg/day or mitotane) 4, 3
• Bilateral disease with dominant gland: Consider staged unilateral adrenalectomy of dominant side first, then reassess need for completion adrenalectomy 2

All patients undergoing unilateral adrenalectomy based on AVS lateralization should be counseled about risk of postoperative adrenal insufficiency, as this occurred in patients with presumed unilateral disease 1.