What is the initial approach to managing a patient with adrenal adenoma?

Initial Management of Adrenal Adenoma

All patients with adrenal adenomas require immediate hormonal evaluation and imaging characterization to determine if the lesion is functional or malignant, regardless of how benign it appears radiologically. 1, 2

Mandatory Initial Workup

Hormonal Evaluation (Required for ALL Patients)

Every adrenal adenoma requires comprehensive endocrine assessment, as approximately 5% of radiologically benign lesions harbor subclinical hormone production requiring treatment 2, 3:

• 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion (cutoff: serum cortisol ≤50 nmol/L or ≤1.8 µg/dL excludes cortisol excess) 1, 4
• Plasma or 24-hour urinary metanephrines to exclude pheochromocytoma 1, 5, 4
• Plasma aldosterone-to-renin ratio only if patient has hypertension and/or hypokalemia 1, 5, 4

Critical pitfall: Skipping hormonal evaluation can lead to undiagnosed pheochromocytoma, which can cause life-threatening hypertensive crisis during any surgical procedure 5. Even if imaging suggests a benign adenoma, functional testing is mandatory 2, 3.

Imaging Characterization

Unenhanced CT with Hounsfield unit (HU) measurement is the first-line imaging test 1:

• HU ≤10 on non-contrast CT definitively indicates a benign adenoma and requires no additional imaging 1, 2, 4
• HU >10 requires second-line imaging with either contrast-enhanced CT with washout protocol or chemical shift MRI to confirm benign characteristics 2, 3
• HU >20 with inhomogeneity raises concern for malignancy and warrants multidisciplinary discussion 4

Biopsy is contraindicated in the initial workup of adrenal adenomas, as it is rarely informative and carries risks including tumor seeding 1, 5

Management Algorithm Based on Size and Function

Small Benign Non-Functional Adenomas (<4 cm)

No further follow-up imaging or functional testing is required if the adenoma meets all three criteria 1, 2, 3:

• Size <4 cm (40 mm)
• HU <10 on unenhanced CT (homogeneous appearance)
• No hormonal hypersecretion on initial screening

Larger Benign Non-Functional Adenomas (≥4 cm)

Repeat imaging at 6-12 months is recommended even if the lesion appears benign, as most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis 1, 2, 3:

• Growth <3 mm/year: No further imaging or functional testing required 1, 2, 3
• Growth >5 mm/year: Consider adrenalectomy after repeating functional workup 1, 2, 3

Functional Adenomas Requiring Surgery

Immediate surgical resection is indicated for 1:

• Pheochromocytomas: Mandatory resection with 1-3 weeks of preoperative alpha-blocker therapy to prevent catecholamine surge 1
• Aldosterone-secreting adenomas: Laparoscopic adrenalectomy after confirmation with saline suppression test and consideration of adrenal vein sampling 1
• Cortisol-secreting adenomas with comorbidities: Surgery should be considered for patients with autonomous cortisol secretion (post-dexamethasone cortisol >50 nmol/L) who have hypertension, type 2 diabetes, or asymptomatic vertebral fractures 1

Minimally invasive surgery (laparoscopic/robotic) is preferred for smaller, contained masses 1

Adenomas with Malignant Features

Surgical resection is recommended for masses with 1:

• Size >4 cm with heterogeneity
• HU >20 with evidence of invasion or necrosis
• Any size with obvious malignant features on imaging

Open adrenalectomy is preferred over laparoscopic approach for masses >5-6 cm with suspected adrenocortical carcinoma, as minimally invasive approaches are associated with higher rates of peritoneal dissemination 1

Special Population Considerations

Expedited evaluation is required for 1, 2:

• Young adults, children, and pregnant patients: Higher likelihood of malignancy; use MRI or low-dose CT for radiation safety 1, 3
• Patients with history of extra-adrenal malignancy: Metastatic risk ranges from 25-72% depending on primary tumor; closer evaluation needed even for smaller lesions 2, 3

Screening for Cortisol-Related Comorbidities

All patients with mild autonomous cortisol secretion (post-dexamethasone cortisol 51-138 nmol/L or 1.9-5.0 mg/dL) should be screened for 1, 4:

• Hypertension
• Type 2 diabetes mellitus
• Asymptomatic vertebral fractures

These comorbidities increase morbidity and mortality risk and influence the decision for surgical intervention 4, 6.