What is the recommended treatment for adrenal adenomas?

Treatment of Adrenal Adenomas

For benign, non-functioning adrenal adenomas <4 cm with characteristic imaging features (≤10 HU on unenhanced CT), no treatment or follow-up is required. 1

Initial Evaluation Framework

All adrenal adenomas require comprehensive hormonal assessment before determining treatment, regardless of imaging characteristics:

• Screen for autonomous cortisol secretion using 1 mg overnight dexamethasone suppression test (cortisol >50 nmol/L [>1.8 µg/dL] indicates mild autonomous cortisol secretion) 1, 2
• Screen for pheochromocytoma with plasma or 24-hour urinary metanephrines, except when unenhanced CT shows <10 HU and no adrenergic symptoms are present 1
• Screen for primary aldosteronism with aldosterone-to-renin ratio in hypertensive or hypokalemic patients 1

Treatment Algorithm by Functional Status

Functioning Adenomas Requiring Surgery

Unilateral adrenalectomy via minimally-invasive surgery is indicated for:

• Cortisol-secreting adenomas with clinically apparent Cushing's syndrome 1
• Aldosterone-secreting adenomas confirmed by adrenal vein sampling 1, 3
• All pheochromocytomas 1

Critical perioperative management:

• Cortisol-producing adenomas require postoperative corticosteroid supplementation until hypothalamic-pituitary-adrenal axis recovery (may take months) 3
• Aldosteronomas benefit from preoperative spironolactone to control hypertension and hypokalemia 3, 4

Mild Autonomous Cortisol Secretion (MACS)

For younger patients with MACS and progressive metabolic comorbidities attributable to cortisol excess (hypertension, type 2 diabetes, osteoporosis), adrenalectomy can be considered after shared decision-making. 1, 2

• Patients not managed surgically require annual clinical screening for new or worsening comorbidities 1
• All MACS patients should be screened and treated for hypertension and diabetes regardless of surgical decision 2, 5

Non-Functioning Adenomas

Surgery is indicated when:

• Size ≥4 cm with radiologically benign features (<10 HU): repeat imaging at 6-12 months, then consider adrenalectomy if growth >5 mm/year after repeating functional work-up 1
• Indeterminate lesions (>10 HU on unenhanced CT): second-line imaging with washout CT or chemical shift MRI, then shared decision-making for repeat imaging in 3-6 months versus surgical resection 1
• Growth >5 mm/year on surveillance imaging after repeating hormonal evaluation 1

No further follow-up required for:

• Benign non-functional adenomas <4 cm with <10 HU 1
• Lesions growing <3 mm/year on follow-up imaging 1
• Myelolipomas and masses containing macroscopic fat 1

Surgical Approach Selection

Minimally-invasive adrenalectomy is preferred for:

• Small tumors (<8 cm) without invasiveness 3
• All functioning adenomas when technically feasible 1, 3

Open adrenalectomy is required for:

• Tumors >8 cm or with imaging features suspicious for malignancy 3
• Suspected adrenocortical carcinoma requiring en bloc resection 1

Medical Management for Non-Surgical Candidates

For aldosterone-producing adenomas in patients who are not surgical candidates:

• Long-term maintenance therapy with spironolactone (mineralocorticoid receptor antagonist) is FDA-approved 4
• This applies to both discrete adenomas and bilateral hyperplasia 4

Critical Pitfalls to Avoid

• Never perform adrenal biopsy on potentially resectable primary adrenal tumors—it is not informative and potentially harmful (risk of tumor seeding) 1
• Always exclude pheochromocytoma before any adrenal intervention including biopsy or surgery to prevent hypertensive crisis 1
• Failure to provide adequate corticosteroid replacement after resection of cortisol-producing adenomas can lead to life-threatening adrenal crisis 3
• Do not assume all bilateral adrenal masses are hyperplasia—measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia and perform adrenal vein sampling as lateralization may still be present 6

Post-Operative Surveillance

For resected functioning adenomas:

• Biochemical testing at 14 days post-surgery to confirm complete resection 3
• For pheochromocytomas: plasma or urinary metanephrines every 3-4 months for 2-3 years, then every 6 months with lifelong surveillance 1, 3
• Higher risk features requiring aggressive follow-up include tumor size >5 cm, extra-adrenal location, and SDHB mutations 3