What is the appropriate management for a patient with a newly diagnosed adrenal adenoma?

Management of Adrenal Adenoma

For a newly diagnosed adrenal adenoma, perform comprehensive hormonal evaluation first, then characterize with unenhanced CT to measure Hounsfield units—if the lesion is <4 cm, benign-appearing (≤10 HU), and hormonally inactive, no further surveillance is required. 1, 2, 3

Initial Hormonal Evaluation (Required for ALL Patients)

Every patient with an adrenal adenoma requires hormonal screening regardless of how benign the mass appears on imaging, because approximately 5% of radiologically benign lesions harbor subclinical hormone production requiring treatment. 1, 2

Mandatory screening tests include:

• 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion (mild autonomous cortisol secretion/MACS), with serum cortisol ≤50 nmol/L excluding autonomous secretion, 51-138 nmol/L indicating possible secretion, and >138 nmol/L confirming autonomous cortisol secretion 2

• Plasma metanephrines or 24-hour urinary metanephrines to exclude pheochromocytoma—this is absolutely mandatory before any surgical consideration to prevent life-threatening intraoperative hypertensive crisis 1, 2

• Aldosterone-to-renin ratio and serum potassium only if the patient has hypertension and/or hypokalemia 1, 2

• Androgen testing (DHEA-S, 17-OH-progesterone, androstenedione, 17-beta-estradiol) only if clinically indicated by virilization or feminization features 2

Imaging Characterization

Unenhanced CT is the gold standard for characterizing adrenal masses using Hounsfield units (HU). 2, 4

• HU ≤10: Definitively benign lipid-rich adenoma, no further imaging needed 1, 2
• HU 10-20: Low malignancy risk, requires second-line imaging 2
• HU >20: 6.3% malignancy risk, requires second-line imaging 2

If HU >10, obtain either washout CT or chemical shift MRI to confirm benign characteristics before proceeding with observation. 1, 3

Size-Based Management Algorithm

Lesions <4 cm (40 mm)

If benign-appearing (≤10 HU), homogeneous, and hormonally inactive: no further follow-up imaging or functional testing is required. 1, 2, 3 This is based on moderate-quality evidence showing a 0% to <1% risk of malignant transformation. 1

Lesions ≥4 cm (40 mm)

Repeat imaging at 6-12 months is required even if radiologically benign, as most surgically resected pheochromocytomas and adrenocortical carcinomas were >40 mm at diagnosis. 2, 3 The malignancy risk increases to 21.1% for nodules ≥40 mm. 3

Growth Rate Thresholds (If Follow-Up Performed)

• <3 mm/year growth: No further imaging or testing 2, 3
• >5 mm/year growth: Consider adrenalectomy after repeating functional workup 2, 3

Management of Functional Adenomas

Pheochromocytoma

Mandatory surgical resection with alpha blocker therapy for 1-3 weeks preoperatively and beta blocker for reflex tachycardia control. 2 Never skip pheochromocytoma screening before surgery. 2

Aldosterone-Secreting Adenoma

Requires confirmatory testing with saline suppression test and bilateral adrenal vein sampling to lateralize production, with laparoscopic adrenalectomy as the treatment of choice. 2

Mild Autonomous Cortisol Secretion (MACS)

Adrenalectomy should be considered only in younger patients with progressive metabolic comorbidities (hypertension, diabetes, osteoporosis) attributable to cortisol excess after shared decision-making. 1 The ability of surgical resection to reverse features of mild hypercortisolism is not well established. 5

Special Population Exceptions

Patients with history of extra-adrenal malignancy have a metastatic risk of 25-72% depending on primary tumor type, and the standard size thresholds do not apply—these patients require closer evaluation regardless of benign imaging characteristics. 1, 2, 3

Young adults, children, and pregnant patients require expedited evaluation as adrenal lesions are more likely malignant in these populations, with MRI preferred over CT when possible for radiation safety. 2, 3

Critical Pitfalls to Avoid

• Never perform adrenal biopsy as part of initial workup due to limited clinical value and risks including tumor seeding and potential hypertensive crisis if undiagnosed pheochromocytoma 2, 3

• Never skip initial hormonal evaluation even if the mass appears benign on imaging, as functional abnormalities occur in approximately 5% of cases and require treatment 1, 2

• Never use laparoscopic approach for suspected adrenocortical carcinoma—open surgery is required for large, invasive tumors to prevent carcinomatosis 2

• Avoid unnecessary repeated imaging for small adrenal masses with benign characteristics, as this leads to increased radiation exposure, patient anxiety, and healthcare costs 1