What is the evaluation and management approach for a patient with an adrenal incidentaloma?

Evaluation and Management of Adrenal Incidentaloma

Initial Evaluation Framework

All patients with an adrenal incidentaloma ≥1 cm require both comprehensive hormonal screening and radiologic characterization, regardless of imaging appearance or symptoms. 1, 2, 3

Focused History and Physical Examination

Obtain a targeted clinical assessment looking for specific signs of hormone excess and malignancy 1:

For cortisol excess:

• Weight gain, central obesity, moon facies, buffalo hump 3
• Purple striae, easy bruising, proximal muscle weakness 3
• Hypertension, diabetes mellitus, osteoporosis 3

For aldosterone excess:

• Resistant hypertension, hypokalemia 3
• Muscle weakness and cramping 3

For catecholamine excess:

• Episodic headaches, palpitations, diaphoresis 2
• Paroxysmal hypertension 2

For malignancy:

• History of extra-adrenal cancer 1
• Constitutional symptoms (weight loss, fatigue) 1

Mandatory Hormonal Testing for All Patients

Every patient requires the following baseline hormonal evaluation 4, 3, 5:

Universal Screening Tests

• 1 mg overnight dexamethasone suppression test (administer 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM) 4, 3, 5
  • Cortisol ≤50 nmol/L (≤1.8 μg/dL): Excludes autonomous cortisol secretion 4, 5
  • Cortisol 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion 4, 5
  • Cortisol >138 nmol/L (>5.0 μg/dL): Confirms autonomous cortisol secretion (formerly "subclinical Cushing's") 4, 5

Conditional Screening Tests

• Pheochromocytoma screening (plasma free metanephrines or 24-hour urinary metanephrines/normetanephrines) if: 4, 3

  • Adrenal mass ≥10 Hounsfield Units (HU) on non-contrast CT 4, 3
  • Any symptoms of catecholamine excess 4, 3
  • Critical pitfall: Failure to exclude pheochromocytoma before biopsy or surgery can be fatal 2

• Primary aldosteronism screening (aldosterone-to-renin ratio) if: 4, 3

  • Hypertension present 4, 3
  • Hypokalemia (serum potassium <3.9 mmol/L) 4, 6
  • Ratio >20 ng/dL per ng/mL/hr confirms hyperaldosteronism 4, 3

• Androgen testing (DHEAS, testosterone) only if: 4, 3

  • Clinical signs of virilization or feminization 4, 3
  • Suspected adrenocortical carcinoma 4, 3

Radiologic Characterization

First-Line Imaging: Non-Contrast CT

Obtain non-contrast CT as the initial imaging study to determine benign vs. malignant features 1, 2, 3:

• <10 HU: Lipid-rich adenoma, definitively benign (100% specificity) 1, 3, 5
• 10-20 HU: Low risk of malignancy (0.5% risk of adrenocortical carcinoma) 1
• >20 HU: Intermediate-to-high risk of malignancy (6.3% risk of adrenocortical carcinoma) 1

Second-Line Imaging for Indeterminate Masses

For masses with HU >10 on non-contrast CT, proceed with 1, 2:

• Washout CT protocol or 1
• Chemical-shift MRI 1, 2

Surgical Indications

Surgery is indicated for the following scenarios 4, 5:

Absolute Indications

• Functional tumors: 4, 5

  • Pheochromocytoma (all cases) 4
  • Aldosterone-secreting adenoma with confirmed primary aldosteronism 4
  • Cortisol-secreting adenoma with overt Cushing's syndrome 4

• Suspicious imaging features: 1, 4, 5

  • Mass >4 cm with inhomogeneous appearance 4, 5
  • Mass >4 cm with HU >20 4, 5
  • Growth >5 mm/year on surveillance imaging (after repeating hormonal workup) 4

Relative Indications

• Mild autonomous cortisol secretion (MACS) with cortisol-related comorbidities: 4, 5
  • Hypertension, type 2 diabetes, osteoporosis, or obesity attributable to cortisol excess 5
  • Consider surgery in an individualized approach after screening for and treating these comorbidities 5

Follow-Up for Non-Surgical Patients

No Further Follow-Up Required

The following lesions require no additional imaging or hormonal testing 4:

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

Surveillance Protocol

For radiologically benign (<10 HU) but ≥4 cm non-functional lesions: 4

• Repeat imaging in 6-12 months 4

For indeterminate masses not meeting surgical criteria: 4

• Repeat functional testing if mass grows >5 mm/year 4
• Growth <3 mm/year: No further follow-up needed 4
• Growth 3-5 mm/year: Continued surveillance appropriate 4

Multidisciplinary Team Approach

Maintain a low threshold for multidisciplinary review involving endocrinologists, surgeons, and radiologists when 1, 2:

• Imaging not consistent with benign lesion 1, 2
• Evidence of hormone hypersecretion 1, 2
• Tumor growth >5 mm/year during follow-up 1, 2
• Adrenal surgery being considered 1, 2

Specialist Roles

• Endocrinologist: Completes comprehensive hormonal evaluation and manages MACS-related comorbidities 2
• Radiologist: Performs and interprets imaging, determines need for second-line studies 2
• Surgeon: Evaluates surgical candidacy, performs minimally invasive adrenalectomy when feasible 2

Critical Pitfalls to Avoid

• Never skip dexamethasone suppression testing, even in small, benign-appearing masses (5.3% of incidentalomas are cortisol-secreting) 3
• Never perform biopsy without first excluding pheochromocytoma (can precipitate fatal hypertensive crisis) 2, 3
• Do not routinely perform adrenal biopsy except when confirming metastatic disease from extra-adrenal malignancy would change management 4, 3
• Do not screen for pheochromocytoma in confirmed lipid-rich adenomas (<10 HU) without symptoms (extremely low yield) 3

Special Considerations

For bilateral adrenal incidentalomas: 4

• Characterize each lesion separately following the same protocol 4
• Measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 4

For patients with known extra-adrenal malignancy: 5, 7

• These are not technically "incidentalomas" but require similar evaluation 1
• Consider biopsy only if confirming adrenal metastasis would alter treatment 4, 3