What is the appropriate management for a patient with an adrenal incidentaloma?

Management of Adrenal Incidentalomas

Initial Evaluation: Two Critical Questions

All patients with adrenal incidentalomas require both imaging characterization to assess malignancy risk and comprehensive hormonal evaluation to exclude functional tumors, regardless of how benign the mass appears radiologically. 1

Imaging Assessment

• Obtain unenhanced CT as the first-line imaging modality to determine Hounsfield units (HU), with ≤10 HU indicating a benign adenoma requiring no further imaging regardless of size 2, 3
• For masses with >10 HU on unenhanced CT, proceed to enhanced CT with washout protocol (absolute washout ≥60% or relative washout ≥40% suggests benign pathology) or chemical shift MRI 2
• Masses >4 cm that are inhomogeneous or have HU >20 carry sufficiently high malignancy risk that surgery is usually the management of choice 3

Mandatory Hormonal Evaluation

Every patient requires the following hormonal work-up, even if the mass appears radiologically benign: 1, 3

• 1 mg overnight dexamethasone suppression test (give 1 mg at 11 PM, measure serum cortisol at 8 AM): cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous cortisol secretion; >50 nmol/L indicates mild autonomous cortisol secretion (MACS) 4, 3
• Plasma free metanephrines or 24-hour urinary fractionated metanephrines to exclude pheochromocytoma before any intervention 1, 4
• Aldosterone-to-renin ratio if hypertension or hypokalemia present (ratio >20 ng/dL per ng/mL/hr suggests primary aldosteronism) 4

Management Algorithm Based on Size, Imaging, and Functional Status

Immediate Surgical Indications

Surgery is indicated for: 1, 2

• All pheochromocytomas (after appropriate alpha-blockade)
• Aldosterone-secreting adenomas causing primary aldosteronism
• Cortisol-secreting masses with clinically apparent Cushing's syndrome
• Masses >4 cm with suspicious imaging features (inhomogeneous, HU >20)
• Any mass growing >5 mm/year after repeating functional work-up 5

Mild Autonomous Cortisol Secretion (MACS)

• For patients with MACS (post-dexamethasone cortisol >50 nmol/L but without overt Cushing's syndrome), screen for and aggressively treat hypertension, type 2 diabetes, osteoporosis, and other metabolic comorbidities 3
• Consider adrenalectomy in younger patients with MACS who have progressive metabolic comorbidities attributable to cortisol excess 1, 3

Non-Functional Benign-Appearing Masses

For masses <4 cm with ≤10 HU: No further imaging or functional testing required 2, 4

For masses ≥4 cm with ≤10 HU (radiologically benign but large): Repeat imaging in 6-12 months 5, 2

For indeterminate masses on imaging: Repeat imaging in 3-6 months versus surgical resection based on shared decision-making, considering patient age, comorbidities, and anxiety level 5

Follow-Up Protocol for Non-Operated Masses

Imaging Follow-Up

• For masses ≥4 cm that are radiologically benign: Repeat unenhanced CT at 6-12 months 5, 2
• If growth <3 mm/year: No further imaging or functional testing required 5
• If growth 3-5 mm/year: Continue surveillance with repeat imaging 4
• If growth >5 mm/year: Repeat functional work-up and consider adrenalectomy 5

Hormonal Follow-Up

• For non-functional masses initially, repeat dexamethasone suppression test is not routinely required unless the mass grows >5 mm/year 4
• Approximately 5% of initially non-functional masses develop new hormonal activity during follow-up, with most developing MACS 1, 6

Special Populations Requiring Expedited Evaluation

Young adults (<40 years), children, and pregnant patients require expedited evaluation because adrenal lesions are more likely malignant in these populations 5, 1

• In these patients, use low-dose CT or chemical shift MRI to minimize radiation exposure 5
• Consider lower thresholds for surgical intervention given higher malignancy risk 1

Patients with known extra-adrenal malignancy require closer evaluation even for smaller lesions, as 25-72% of adrenal masses in this population represent metastases depending on primary tumor type 1

Bilateral Adrenal Incidentalomas

• Characterize each lesion separately using the same algorithm as for unilateral masses 5, 2
• Measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 5, 2
• Assess for adrenal insufficiency if bilateral infiltrative disease, metastases, or hemorrhage suspected 5

Critical Pitfalls to Avoid

Never perform adrenal biopsy routinely for incidentaloma work-up, as it carries risk of tumor seeding in suspected adrenocortical carcinoma and is rarely indicated except when confirming metastatic disease from extra-adrenal malignancy would change management 1, 4

Do not skip hormonal evaluation based on benign imaging appearance alone, as approximately 5% of radiologically benign incidentalomas harbor subclinical hormone production requiring treatment 1

Avoid unnecessary repeated imaging in masses <4 cm with ≤10 HU, as this leads to increased radiation exposure, patient anxiety, and healthcare costs without clinical benefit 1, 2