What is the management approach for adrenal incidentaloma?

Management of Adrenal Incidentaloma

All patients with adrenal incidentalomas require both comprehensive hormonal evaluation and radiological characterization to determine malignancy risk, with management decisions driven by imaging features, size, and functional status. 1

Initial Radiological Assessment

Unenhanced CT is the mandatory first-line imaging modality for all adrenal incidentalomas. 2, 3

Benign Features (No Further Imaging Required)

• Homogeneous lesions ≤10 Hounsfield Units (HU) on non-contrast CT are definitively benign regardless of size and require no additional imaging 1, 4
• Myelolipomas and masses containing macroscopic fat are benign and need no further workup 1, 2

Indeterminate Features (Require Second-Line Imaging)

• Masses >10 HU or with inhomogeneous appearance warrant CT with washout protocol or chemical-shift MRI 1
• CT washout values of ≥60% absolute washout or ≥40% relative washout indicate benign pathology 3
• MRI is preferred for pregnant women and patients <40 years old 1, 3

High-Risk Features (Surgical Consideration)

• Masses >4 cm with inhomogeneous appearance or >20 HU have sufficiently high malignancy risk that surgery is the usual management choice 4
• Any mass with suspicious radiological features regardless of size warrants multidisciplinary discussion 1

Mandatory Hormonal Evaluation

Every patient requires complete hormonal screening regardless of symptoms or imaging appearance. 1, 4

Universal Screening Tests

• 1 mg overnight dexamethasone suppression test (administer 1 mg at 11 PM, measure serum cortisol at 8 AM) 2, 4
  • Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous cortisol secretion 2, 4
  • Cortisol 51-138 nmol/L suggests possible autonomous cortisol secretion 2
  • Cortisol >138 nmol/L indicates autonomous cortisol secretion requiring intervention consideration 5
• Plasma free metanephrines or 24-hour urinary fractionated metanephrines to exclude pheochromocytoma 2, 4

Conditional Screening Tests

• Aldosterone-to-renin ratio if hypertension and/or hypokalemia present (ratio >20 ng/dL per ng/mL/hr confirms hyperaldosteronism) 2, 3
• Serum androgens (DHEAS, testosterone) only if clinical virilization or suspected adrenocortical carcinoma 2
• For bilateral incidentalomas, measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1, 3

Management Algorithm Based on Size, Imaging, and Function

Immediate Surgical Indications

Surgery is indicated for: 1, 2

• Any hormonally active tumor (pheochromocytoma, aldosteronoma, cortisol-secreting with overt Cushing's syndrome) 2, 3
• Masses >4 cm with suspicious imaging features (inhomogeneous, >20 HU) 4
• Any mass growing >5 mm/year on surveillance (after repeating hormonal workup) 2, 3

Mild Autonomous Cortisol Secretion (MACS)

For patients with post-dexamethasone cortisol >50 nmol/L without overt Cushing's syndrome: 4

• Screen for and aggressively treat cortisol-related comorbidities (hypertension, type 2 diabetes, osteoporosis) 4, 5
• Consider surgery if significant comorbidities potentially attributable to cortisol excess are present 4, 5
• This represents a shift from older terminology of "subclinical Cushing's syndrome" as evidence shows increased morbidity and mortality 4

Observation Without Surgery

No further imaging or hormonal follow-up required for: 1, 2

• Benign non-functional lesions <4 cm with ≤10 HU 1, 2
• Myelolipomas and masses with macroscopic fat 1, 2

Surveillance imaging required for: 1, 3

• Radiologically benign (≤10 HU) but ≥4 cm non-functional lesions: repeat imaging at 6-12 months 2, 3
• Indeterminate masses 10-20 HU and <4 cm: repeat imaging at 12 months, then annually for 1-2 years if stable 1, 3

Follow-Up Protocol for Non-Surgical Cases

Imaging Surveillance

• For masses requiring follow-up, perform unenhanced CT at 12 months 3
• If stable at 12 months, continue annual clinical follow-up for 4 years total 1, 3
• Discontinue imaging if no growth after 1-2 years of stability 3

Hormonal Surveillance

• Annual hormonal screening for 4-5 years is recommended for masses >3 cm due to 17% risk of new hormone secretion at 1 year, 29% at 2 years, and 47% at 5 years 1
• No repeat hormonal testing needed for confirmed benign lesions <4 cm 2
• If mass grows >5 mm/year, repeat complete functional workup before surgical decision 2

Critical Pitfalls to Avoid

Never perform adrenal biopsy routinely - only consider when metastatic disease from extra-adrenal malignancy would directly change management, and only after pheochromocytoma is definitively excluded 2, 3, 6

Do not skip pheochromocytoma screening - failure to exclude this before surgery or biopsy can be fatal 2, 4

Medications interfere with hormonal testing - hold interfering medications when possible before testing (particularly for aldosterone-renin ratio and metanephrines) 2

Each lesion in bilateral incidentalomas must be characterized separately using the same protocol as unilateral masses 2, 3

Multidisciplinary discussion is mandatory when imaging is indeterminate, hormone hypersecretion is present, significant growth occurs, or surgery is considered 1, 2, 3