Adrenalectomy is performed to remove functional masses such as adrenocortical hyperplasia (Cushing's disease), cortisol-secreting adenoma or adenocarcinoma (Cushing's syndrome), aldosterone-secreting adenoma (Conn's syndrome), pheochromocytoma, and adrenal causes of feminizing or virilizing syndromes. Non-functional masses that are also treated with adrenalectomy include adrenal adenocarcinoma, symptomatic adrenal cysts or angiomyolipomas, adrenal incidentalomas >4 cm discovered on imaging studies, and isolated adrenal metastases.

With functioning tumors confirmed biochemically, a CT or MRI is performed to determine the side of the neoplasm as well as its size, local invasion, and hepatic metastases. A 131I-MIBG scan is also performed in patients with a diagnosis of pheochromocytoma to localize occult second tumors or metastatic disease to the liver, lung, or bone. Selective venous sampling from the adrenal veins and inferior vena cava is useful to confirm the diagnosis of an aldosterone-secreting adenoma verses bilateral adrenal micronodular hyperplasia of the zona glomerulosa.

Preoperative alpha and, occasionally, beta blockade is necessary before all adrenalectomies performed for pheochromocytomas. Preoperative administration of spironolactone may help reverse persistent hypokalemia in patients with aldosterone-secreting adenomas. Perioperative glucocorticoid supplementation is used in patients undergoing adrenalectomies for Cushing's disease or syndrome.

A laparoscopic approach with or without hand-assist under general anesthesia is used when non-malignant adrenal lesions under 10–12 cm are to be excised. An open anterior transabdominal, flank extraperitoneal, or posterior (with resection of the 12th rib) retroperitoneal approach under general anesthesia is used when adrenal adenocarcinoma, a mass >10–12 cm, extensive adhesions, or portal hypertension is present.