What is the recommended treatment for a functional adrenal adenoma, such as a cortisol‑producing or aldosterone‑producing tumor?

Treatment of Adrenal Adenoma

Functional adrenal adenomas require surgical removal via minimally invasive adrenalectomy, while benign non-functional adenomas <4 cm need no treatment or follow-up. 1

Cortisol-Producing Adenomas

Overt Cushing's Syndrome

• Unilateral adrenalectomy is mandatory for patients with clinically apparent Cushing's syndrome from a cortisol-secreting adenoma. 1
• Minimally invasive surgery (laparoscopic or retroperitoneoscopic approach) should be performed when technically feasible. 1
• No adrenal venous sampling is required—imaging combined with biochemical testing (1 mg dexamethasone suppression test showing cortisol >50 nmol/L or >1.8 µg/dL) is sufficient to confirm the diagnosis and lateralize the lesion. 2, 3

Mild Autonomous Cortisol Secretion (MACS)

• Younger patients with MACS who have progressive metabolic comorbidities (hypertension, type 2 diabetes, obesity, osteoporosis) attributable to cortisol excess should be considered for adrenalectomy after shared decision-making. 1, 3
• Screen all patients with MACS for cortisol-related comorbidities and ensure these are appropriately treated regardless of surgical decision. 3
• Patients not managed surgically require annual clinical screening for new or worsening metabolic complications. 1

Common pitfall: Do not order adrenal venous sampling for cortisol-producing adenomas—this invasive procedure is reserved exclusively for primary aldosteronism and will delay appropriate surgical management. 2

Aldosterone-Producing Adenomas

Diagnostic Pathway

• Screen hypertensive patients (especially those with hypokalemia) using aldosterone-to-renin ratio. 1, 4
• Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy to confirm unilateral aldosterone hypersecretion and distinguish adenoma from bilateral hyperplasia. 1, 2, 4
• This lateralization step is critical because it determines whether surgery or medical therapy is appropriate—imaging alone cannot reliably make this distinction. 2, 4

Surgical Management

• Unilateral adrenalectomy should be performed for confirmed unilateral aldosterone-secreting adenomas. 1
• Minimally invasive surgery is preferred when feasible. 1
• Both total and partial adrenalectomy achieve equivalent blood pressure control and normalization of plasma renin activity and aldosterone levels at long-term follow-up. 5

Medical Management Alternative

• For bilateral hyperplasia or patients who decline/are not candidates for surgery, mineralocorticoid receptor antagonists (MRAs) are first-line medical therapy. 4
• Spironolactone is preferred over other MRAs due to lower cost and greater availability, though all MRAs have similar efficacy when titrated to equivalent potencies. 4
• Monitor renin levels during MRA therapy and titrate the dose to increase suppressed renin if hypertension remains uncontrolled. 4

Common pitfall: Proceeding to adrenalectomy without AVS in primary aldosteronism risks removing the wrong adrenal gland or performing unnecessary surgery in patients with bilateral disease who would benefit more from medical therapy. 2, 4

Pheochromocytoma

• Adrenalectomy is mandatory for all pheochromocytomas due to risk of hypertensive crisis and cardiovascular mortality. 1
• Screen with plasma or 24-hour urinary metanephrines in patients with adrenal masses >10 HU on non-contrast CT or those with signs/symptoms of catecholamine excess. 1
• Minimally invasive surgery should be performed when feasible. 1

Critical safety measure: Always exclude pheochromocytoma before any adrenal biopsy to prevent potentially fatal hypertensive crisis. 1

Non-Functional Adenomas

No Treatment Required

• Benign non-functional adenomas <4 cm with radiologically benign features (<10 HU on non-contrast CT) require no further follow-up imaging or functional testing. 1
• This applies equally to myelolipomas and other small masses containing macroscopic fat. 1

Surveillance Protocol

• Non-functional lesions ≥4 cm but radiologically benign (<10 HU) should undergo repeat imaging in 6-12 months. 1
• Adrenalectomy should be considered for lesions growing >5 mm/year after repeating functional work-up to exclude interval development of hormone excess or malignancy. 1
• No further imaging is required for lesions growing <3 mm/year. 1

Suspected Adrenocortical Carcinoma

• Minimally invasive adrenalectomy can be offered if the tumor can be safely resected without rupturing the capsule. 1
• Open adrenalectomy should be considered for larger tumors or those with locally advanced features, lymph node metastases, or tumor thrombus in the renal vein/IVC. 1
• Perform 1 mg overnight dexamethasone suppression test in all patients with adrenal adenoma to screen for co-secretion of cortisol. 4, 3

Key principle: The decision to operate on any adrenal adenoma is guided by hormone excess status, likelihood of malignancy based on imaging characteristics (size, HU density, homogeneity), patient age, general health, and patient preference—but functional adenomas producing aldosterone, cortisol (with overt Cushing's), or catecholamines have clear surgical indications that override conservative management. 1, 3