Adrenal Cushing's syndrome is characterized by ACTH-independent hypercortisolism. Adrenal vein sampling (AVS) is not routinely employed prior to management decisions, and few studies have investigated the value of AVS in this population. We assessed whether AVS provides a diagnostic benefit for treatment planning.

Six patients with imaging and biochemical evidence of adrenal Cushing's syndrome undergoing AVS at our institution from 2015 to 2020 were analyzed retrospectively, including demographic and clinical characteristics. AVS lateralization index was determined by comparing the (cortisol/ipsilateral reference hormone) ratios of both adrenal veins. lateralization index of 2 or greater was considered diagnostic of unilateral disease. Post-management clinical improvement was defined as serum cortisol normalization, symptomatic improvement, or both.

Cross-sectional imaging noted bilateral adrenal enlargement or nodules in three patients, and unilateral nodules in three patients. AVS results were discordant with imaging in three patients. Treatment included medical management in two patients, percutaneous radiofrequency ablation in one patient, and laparoscopic adrenalectomy in two patients. One patient was lost to follow up. AVS results aided management planning in five patients, definitively changing treatment from surgery to medical management in one patient. All five patients demonstrated clinical improvement.

AVS offered useful information for determining appropriate management of adrenal Cushing's syndrome, especially distinguishing unilateral from bilateral disease. Even in bilateral disease, AVS may show a dominant gland, potentially allowing a staged unilateral adrenalectomy, before assessing the need for completion adrenalectomy or medical management. Larger studies are needed to better establish whether AVS offers significant benefit for this population.