What is the appropriate workup for a patient with an adrenal adenoma identified on CT?

Workup for Adrenal Adenoma Identified on CT

All patients with an adrenal adenoma on CT require both hormonal evaluation and radiological characterization, regardless of whether the lesion appears benign, because approximately 5-12% of incidentalomas have subclinical hormone production requiring treatment. 1, 2

Initial Radiological Assessment

Hounsfield Unit Measurement

• Obtain a dedicated non-contrast CT to measure the lesion's attenuation in Hounsfield Units (HU) if not already performed 1, 3
• If ≤10 HU: The lesion is definitively a benign lipid-rich adenoma from an imaging standpoint 1, 3
• If >10 HU: Proceed to second-line imaging with either delayed contrast-enhanced CT (washout protocol at 10-15 minutes) or chemical shift MRI 1
  • Enhancement washout >50% at 10-15 minutes indicates benign adenoma 1
  • Chemical shift MRI showing signal intensity loss on opposed-phase imaging confirms adenoma 1

Size-Based Risk Stratification

• <3 cm: Almost all are benign in patients without cancer history 1, 4
• 3-5 cm: Intermediate risk; requires second-line imaging regardless of HU 3
• ≥4 cm: Higher malignancy risk; requires follow-up imaging even if radiologically benign 1, 3
• >5 cm: Strong consideration for surgical removal due to elevated malignancy risk 3, 4

Mandatory Hormonal Evaluation

Screen for Pheochromocytoma (MUST be done before any biopsy or surgery)

• Measure plasma free metanephrines (sensitivity 96-100%, specificity 89-98%) OR 24-hour urinary fractionated metanephrines (sensitivity 86-97%, specificity 86-95%) 5, 2
• This testing is absolutely mandatory before any invasive procedure to prevent life-threatening hypertensive crisis 5, 6
• For plasma testing, ideally collect from indwelling catheter after 30 minutes supine to minimize false positives 5

Screen for Autonomous Cortisol Secretion

• Perform 1 mg overnight dexamethasone suppression test in all patients 6, 2
• Cortisol >138 nmol/L (>5.0 μg/dL) indicates autonomous hypersecretion requiring treatment 6
• This detects subclinical Cushing syndrome present in 5-12% of incidentalomas 1

Screen for Primary Aldosteronism

• Measure aldosterone-to-renin ratio only if patient has hypertension or unexplained hypokalemia 1, 2

Additional Testing if Adrenocortical Carcinoma Suspected

• Measure sex hormones (DHEAS) and steroid precursors if imaging suggests malignancy (inhomogeneous, irregular margins, HU >20) 1, 4

Follow-Up Imaging Protocol

For Radiologically Benign Lesions (<10 HU)

• <4 cm: No follow-up imaging needed per ACR and ESE guidelines 1
• ≥4 cm: Repeat imaging at 6-12 months to assess for growth 1, 3
• AACE/AAES recommend more conservative approach: reimaging at 3-6 months, then annually for 1-2 years 1

For Hormonally Inactive Benign Lesions

• ESE: No additional hormonal testing if initial workup normal 1
• AACE/AAES and KES: Annual hormonal screening for 4-5 years, particularly if lesion >3 cm 1

For Indeterminate Lesions

• Repeat imaging in 3-6 months 1, 3
• Consider PET-CT if patient has history of malignancy (lung, colon, lymphoma, neuroendocrine tumors) 1, 3
• Surgery indicated if lesion grows >5 mm/year or shows appreciable growth 1, 3

Critical Pitfalls to Avoid

• Never perform adrenal biopsy without first excluding pheochromocytoma biochemically—this can cause fatal hypertensive crisis 5, 6, 3
• Do not use size alone to determine malignancy risk; small lesions with high HU can still be malignant 6
• Do not skip hormonal workup even if lesion appears radiologically benign, as 5-12% have subclinical hormone production 1, 2
• Avoid contrast-enhanced CT until pheochromocytoma is excluded, as contrast can trigger catecholamine crisis 5