What is the recommended diagnostic work-up for an adult patient with no prior medical history presenting with an adrenal mass lesion?

Diagnostic Work-Up for Adrenal Mass Lesions

All patients with an incidentally discovered adrenal mass require both radiologic characterization and comprehensive hormonal evaluation, regardless of imaging appearance, as approximately 5% of radiologically benign lesions harbor subclinical hormone production requiring treatment. 1, 2

Initial Clinical Assessment

Obtain focused history and physical examination targeting: 1

• Signs of cortisol excess: Weight gain, proximal muscle weakness, facial plethora, wide purple striae, easy bruising, glucose intolerance, unexplained osteopenia 1, 3
• Signs of aldosterone excess: Hypertension, hypokalemia, muscle weakness 1
• Signs of catecholamine excess: Episodic headaches, palpitations, diaphoresis, hypertension (particularly paroxysmal) 1
• Signs of androgen excess: Virilization, hirsutism, menstrual irregularities 1
• History of extra-adrenal malignancy: Critical as metastatic risk is 25-72% depending on primary tumor 2, 4
• Age considerations: Young adults, children, and pregnant patients require expedited evaluation as lesions are more likely malignant 1

Radiologic Characterization Algorithm

First-Line Imaging: Non-Contrast CT 1

Measure Hounsfield Units (HU) to distinguish benign from indeterminate lesions:

• HU ≤10: Definitively benign lipid-rich adenoma; no further imaging needed unless ≥4 cm 1, 2, 5
• HU >10: Indeterminate; requires second-line imaging 1, 6

The specificity of HU ≤10 for benign adenoma is 100%, with 0% risk of adrenocortical carcinoma when HU <10 1, 7

Second-Line Imaging (for HU >10): 1, 6

Choose either:

• Washout CT: Absolute washout >60% or relative washout >40% indicates benign adenoma 7
• Chemical shift MRI: Loss of signal intensity on out-of-phase images indicates lipid-rich adenoma 6, 7

Critical caveat: Approximately 1/3 of pheochromocytomas may show washout in the adenoma range (false negative), and malignant masses can also demonstrate washout 6. Therefore, hormonal evaluation cannot be bypassed based on imaging alone.

Special Imaging Considerations:

• Suspected pheochromocytoma: Chemical shift MRI preferred over contrast-enhanced CT due to hypertensive crisis risk from IV contrast 6
• Radiation safety concerns (young adults, children, pregnant patients): Low-dose CT or chemical shift MRI preferred 1, 6

Mandatory Hormonal Evaluation

All patients require screening for hormone excess, regardless of imaging characteristics: 1, 4

1. Autonomous Cortisol Secretion (Required for ALL patients): 1, 5

• Test: 1 mg overnight dexamethasone suppression test 1, 4
• Interpretation:
  • Cortisol ≤50 nmol/L (≤1.8 µg/dL): Rules out autonomous cortisol secretion 5
  • Cortisol >50 nmol/L (>1.8 µg/dL): Mild autonomous cortisol secretion (MACS) present 5

2. Pheochromocytoma Screening: 1, 5

Indications for screening:

• HU >10 on non-contrast CT 1
• Any signs/symptoms of catecholamine excess 1

Exception: May omit screening if unequivocal adrenocortical adenoma (HU <10) AND no adrenergic symptoms 1

Test: Plasma or 24-hour urinary metanephrines 1, 4

3. Primary Aldosteronism Screening: 1

Indications: Hypertension and/or hypokalemia 1, 4

Test: Aldosterone-to-renin ratio 1

4. Androgen Excess Screening: 1

Indications:

• Suspected adrenocortical carcinoma 1
• Clinical signs of virilization 1

Test: Serum androgen levels (DHEA-S, testosterone) 1

Size-Based Management Thresholds

Benign Non-Functional Lesions (HU <10):

• <4 cm: No further imaging or functional testing required 1, 2
• ≥4 cm: Repeat imaging in 6-12 months despite benign appearance 1, 2

Indeterminate Lesions:

• Any size with HU >10: Requires second-line imaging 1, 6
• >4 cm with inhomogeneous appearance or HU >20: High malignancy risk; surgery usually indicated 5

Growth Rate on Follow-Up:

• <3 mm/year: No further imaging or functional testing 1
• >5 mm/year: Consider adrenalectomy after repeating functional work-up 1

Role of Adrenal Biopsy

Adrenal biopsy should NOT be performed routinely. 1, 4

Reserved only for cases where noninvasive techniques are equivocal with high suspicion for metastatic disease in patients with known extra-adrenal malignancy. 2

Critical safety requirement: Must exclude pheochromocytoma hormonally before any biopsy to prevent hypertensive crisis. 6

Multidisciplinary Review Triggers

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

• Imaging not consistent with benign lesion
• Evidence of hormone hypersecretion
• Tumor growth during follow-up
• Adrenal surgery being considered

Common Pitfalls to Avoid

• Never skip hormonal evaluation even for radiologically benign lesions, as 5% have subclinical hormone production requiring treatment 2, 4
• Never perform contrast-enhanced imaging before excluding pheochromocytoma hormonally, as IV contrast can precipitate hypertensive crisis 6
• Never assume benignity based on size alone in patients with extra-adrenal malignancy history, as metastatic risk is 25-72% 2, 4
• Never order routine adrenal biopsy, as this carries unnecessary risks and is rarely indicated 1, 4