What is the initial evaluation and management of adrenal incidentaloma?

Initial Evaluation and Management of Adrenal Incidentaloma

All patients with adrenal incidentalomas ≥1 cm require both biochemical screening for hormone excess AND radiological characterization with non-contrast CT, regardless of imaging appearance or symptoms. 1

Definition and Initial Approach

An adrenal incidentaloma is defined as an adrenal mass ≥1 cm discovered on imaging performed for unrelated indications, excluding masses found during cancer staging. 1

The evaluation addresses two critical questions that directly impact morbidity and mortality:

• Is the mass hormonally active? (to prevent hypertensive crisis, metabolic complications, or sudden death)
• Is the mass malignant? (to enable timely surgical intervention)

1, 2

Step 1: Focused History and Physical Examination

Target specific signs of hormone excess that increase cardiovascular morbidity and mortality: 1

Cortisol Excess (Cushing's syndrome)

• Weight gain with central obesity, moon facies, buffalo hump
• Purple striae (>1 cm wide), easy bruising
• Proximal muscle weakness
• Hypertension, diabetes, osteoporosis 1, 3

Aldosterone Excess

• Resistant hypertension (requiring ≥3 antihypertensives)
• Hypokalemia, muscle weakness, cramping 3, 4

Catecholamine Excess (Pheochromocytoma)

• Critical to identify: Episodic or sustained hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, pallor
• Missing this diagnosis can cause fatal hypertensive crisis during any surgical procedure 3, 5

Androgen/Estrogen Excess

• Virilization in women (hirsutism, deepening voice, clitoromegaly)
• Feminization in men (gynecomastia, testicular atrophy) 4

Step 2: Radiological Characterization

Non-contrast CT is the mandatory first-line imaging study. 1, 3

Interpretation Algorithm:

Benign (no further imaging needed):

• Homogeneous, well-circumscribed mass with <10 Hounsfield Units (HU)
• 100% of such masses in surgical series were benign
• 0% risk of adrenocortical carcinoma 1, 3

Indeterminate (requires second-line imaging):

• HU 10-20: 0.5% risk of malignancy
• HU >20: 6.3% risk of malignancy
• Obtain either washout CT or chemical shift MRI 1

Important caveat: Approximately 1/3 of pheochromocytomas can washout like adenomas, and 1/3 of adenomas don't washout in the typical range—clinicians must be aware of these false positives/negatives. 1

Step 3: Mandatory Biochemical Screening

ALL patients require screening for autonomous cortisol secretion, regardless of symptoms or imaging characteristics. 1, 3

Required Tests:

1. Autonomous Cortisol Secretion (MANDATORY for all patients):

• 1 mg overnight dexamethasone suppression test (preferred screening test)
• Interpretation:
  • ≤50 nmol/L (1.8 μg/dL): Excludes hypersecretion
  • 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous secretion

  • 138 nmol/L (>5.0 μg/dL): Autonomous cortisol secretion confirmed 1, 3

2. Pheochromocytoma Screening:

• Screen if: Mass >10 HU on non-contrast CT OR any symptoms of catecholamine excess
• Do NOT screen if: Unequivocal adenoma (HU <10) AND no symptoms
• Test: Plasma metanephrines or 24-hour urinary metanephrines 1, 3

3. Primary Aldosteronism Screening:

• Screen if: Hypertension and/or hypokalemia present
• Test: Aldosterone-to-renin ratio (ratio >20 ng/dL per ng/mL/hr has excellent sensitivity/specificity)
• If positive: Adrenal vein sampling required before offering adrenalectomy 1, 3

4. Androgen Excess:

• Screen if: Suspected adrenocortical carcinoma OR clinical signs of virilization/feminization 1

Step 4: Management Decisions

Indications for Surgery (to prevent mortality from malignancy or hormone excess):

Absolute indications for adrenalectomy:

• Clinically apparent Cushing's syndrome (unilateral adrenalectomy, minimally invasive when feasible)
• Aldosterone-secreting adenomas (after adrenal vein sampling confirmation)
• Pheochromocytomas (minimally invasive when feasible) 1

Relative indications:

• Younger patients with mild autonomous cortisol secretion AND progressive metabolic comorbidities (shared decision-making required; if not surgical, annual screening for worsening comorbidities)
• Suspected adrenocortical carcinoma <5 cm (minimally invasive if capsule can remain intact)
• Larger or locally advanced adrenocortical carcinomas (open adrenalectomy) 1

Follow-up for Non-Surgical Patients:

No further follow-up needed:

• Benign non-functional adenomas <4 cm with HU <10
• Myelolipomas or other masses with macroscopic fat 1

Repeat imaging in 6-12 months:

• Non-functional lesions that are radiologically benign (HU <10) but ≥4 cm 1

Consider adrenalectomy if:

• Growth >5 mm/year (repeat functional workup first)
• No further imaging needed if growth <3 mm/year 1

Indeterminate non-functional lesions:

• Shared decision-making: repeat imaging in 3-6 months versus surgical resection 1

Critical Pitfalls to Avoid

Never biopsy an adrenal incidentaloma routinely—only consider if metastatic disease from extra-adrenal malignancy would change management, and ONLY after excluding pheochromocytoma (risk of hypertensive crisis and tumor seeding). 1, 5

Always exclude pheochromocytoma before any surgery (including unrelated procedures like cataract surgery)—undiagnosed pheochromocytoma causes life-threatening hypertensive crisis intraoperatively. 5

Maintain low threshold for multidisciplinary review (endocrinology, surgery, radiology) when imaging is not clearly benign, hormone hypersecretion is present, tumor grows >5 mm/year, or surgery is considered. 1, 4