What is the recommended management approach for adrenal incidentaloma?

Management of Adrenal Incidentaloma

All patients with adrenal incidentalomas require both complete radiological characterization with unenhanced CT and comprehensive hormonal screening regardless of symptoms or imaging appearance. 1, 2, 3

Initial Radiological Assessment

First-line imaging is mandatory unenhanced CT to determine Hounsfield Units (HU): 1, 2, 3

• Lesions ≤10 HU that are homogeneous and well-circumscribed are definitively benign regardless of size and require no further imaging or workup 1, 2
• Myelolipomas and masses containing macroscopic fat are benign and need no additional evaluation 2, 3
• For indeterminate masses on unenhanced CT, proceed to second-line imaging with either washout CT (absolute washout ≥60% or relative washout ≥40% suggests benign) or chemical-shift MRI 1, 2
• Risk of adrenocortical carcinoma is 0% when HU <10,0.5% when HU 10-20, and 6.3% when HU >20 1

Mandatory Hormonal Evaluation

Every patient requires complete hormonal screening regardless of symptoms or imaging characteristics: 1, 4, 3

Universal Screening Tests:

• 1 mg overnight dexamethasone suppression test (give 1 mg at 11 PM, measure cortisol at 8 AM) 1, 4, 3
  • Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous cortisol secretion 4, 5
  • Cortisol 51-138 nmol/L suggests possible autonomous cortisol secretion 4
  • Cortisol >138 nmol/L indicates autonomous cortisol secretion (formerly called subclinical Cushing's) 4, 5

Conditional Screening Tests:

• Plasma free metanephrines or 24-hour urinary fractionated metanephrines for all masses >10 HU or any patient with symptoms of catecholamine excess (hypertension, headaches, palpitations, diaphoresis) 1, 4, 3

  • Critical pitfall: Never perform biopsy or surgery without first excluding pheochromocytoma—failure to do so can be fatal 3

• Aldosterone-to-renin ratio for patients with hypertension and/or hypokalemia 1, 4

  • Ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity 4
  • Adrenal vein sampling is required before offering surgery for primary aldosteronism 1

• Serum androgens (DHEAS, testosterone, 17-hydroxyprogesterone) only when clinical signs of virilization/feminization are present or adrenocortical carcinoma is suspected 1, 4

Management Algorithm Based on Size, Imaging, and Hormonal Status

Immediate Surgical Indications:

Surgery is indicated for: 1, 2, 3

• Any hormonally active tumor (pheochromocytoma, aldosterone-secreting adenoma, cortisol-secreting adenoma with overt Cushing's syndrome) 1, 3
• Masses >4 cm with suspicious imaging features (inhomogeneous, HU >20) 1, 2, 3
• Any mass growing >5 mm/year on surveillance (repeat hormonal workup first) 1, 2, 3
• Lesions with radiological features concerning for adrenocortical carcinoma 1, 2

Management of Mild Autonomous Cortisol Secretion (MACS):

For patients with post-dexamethasone cortisol >50 nmol/L without overt Cushing's syndrome: 3, 5

• Screen aggressively for and treat cortisol-related comorbidities (hypertension, type 2 diabetes, osteoporosis, obesity) 3, 5
• Consider surgery in an individualized approach when relevant comorbidities are present that may be attributable to cortisol excess 3, 5

No Surgery Required:

No further imaging or hormonal testing needed for: 2, 3

• Benign non-functional lesions <4 cm with ≤10 HU 2, 3
• Myelolipomas 2, 3
• Small masses containing macroscopic fat 2, 3

Follow-Up Protocol for Non-Surgical Cases

For Radiologically Benign (≤10 HU) but ≥4 cm Non-Functional Lesions:

• Repeat unenhanced CT at 12 months 2, 3
• Discontinue imaging if stable after 1-2 years 2, 3

For Masses Requiring Surveillance:

• Perform unenhanced CT at 12 months 2, 3
• Annual hormonal screening for 4-5 years for masses >3 cm (risk of developing new hormone secretion) 1, 3
• If growth <3 mm/year, no further imaging or functional testing required 4
• If growth 3-5 mm/year, continued surveillance may be appropriate 4
• If growth >5 mm/year, repeat complete hormonal workup before considering surgery 1, 4

Special Considerations

Bilateral Adrenal Incidentalomas:

• Each lesion must be characterized separately using the same protocol as unilateral masses 2, 3
• Measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 2, 3

Role of Adrenal Biopsy:

Adrenal biopsy should NOT be performed routinely 1, 3

• Only consider when diagnosis of metastatic disease from extra-adrenal malignancy would directly change management 1, 3
• Must definitively exclude pheochromocytoma before any biopsy attempt 3

Multidisciplinary Discussion:

Low threshold for multidisciplinary team review (endocrinology, surgery, radiology) when: 1, 3

• Imaging is not consistent with benign lesion 1, 3
• Evidence of hormone hypersecretion is present 1, 3
• Tumor has grown significantly during follow-up 1, 3
• Adrenal surgery is being considered 1, 3

Critical Pitfalls to Avoid

• Never skip pheochromocytoma screening before surgery or biopsy in masses >10 HU or with any adrenergic symptoms—this can be fatal 3
• Do not perform routine adrenal biopsy for workup of incidentalomas 1, 3
• Do not assume bilateral masses have the same etiology—characterize each separately 2, 3
• Be aware that medications can interfere with hormone testing; consider holding interfering medications when possible 4
• Do not order extensive androgen testing for unilateral masses with minimal growth unless virilization signs are present 4