How should an adrenal adenoma be evaluated?

Assessment of Adrenal Adenoma

All patients with an adrenal adenoma should undergo both imaging characterization to confirm benignity and hormonal screening to exclude autonomous hormone secretion, regardless of whether the mass appears benign on initial imaging. 1

Initial Imaging Assessment

Obtain non-contrast CT as the first-line imaging test to characterize any adrenal mass. 1

• Masses with attenuation ≤10 Hounsfield Units (HU) on unenhanced CT are diagnostic of benign adenoma with 100% specificity and require no further imaging characterization. 1, 2
• Masses with HU 10-20 carry a 0.5% risk of adrenocortical carcinoma (ACC), while those >20 HU carry a 6.3% risk. 1
• The 4 cm size threshold is no longer required to define a benign adenoma that needs no further imaging follow-up, provided the HU is ≤10. 3

Second-Line Imaging for Indeterminate Masses

If the mass shows >10 HU on non-contrast CT, proceed with either contrast-enhanced washout CT or chemical shift MRI. 1

Contrast-Enhanced Washout CT:

• Absolute washout ≥60% or relative washout ≥40% suggests benign adenoma. 4, 2
• Critical limitation: Approximately one-third of pheochromocytomas can washout in the adenoma range, and one-third of adenomas do not washout appropriately; malignant masses can also show adenoma-range washout. 1

Chemical Shift MRI:

• Homogeneous signal intensity drop on out-of-phase images is diagnostic of lipid-rich adenoma. 1, 4
• Heterogeneous signal drop is controversial as minute fat can be present in pheochromocytoma, ACC, and some metastases. 1

Mandatory Hormonal Screening

All patients with adrenal adenomas require screening for autonomous cortisol secretion, regardless of imaging characteristics. 1

Cortisol Excess Screening

Perform 1 mg overnight dexamethasone suppression test (DST) in all patients. 1, 5, 6

• This is the preferred screening test for identifying autonomous cortisol secretion. 1, 5
• Screen even if the mass shows <10 HU, because imaging cannot exclude mild autonomous cortisol secretion (MACS), which occurs in 30-50% of adrenal incidentalomas and is associated with cardiovascular morbidity and metabolic abnormalities. 7, 3

Look for clinical features of hypercortisolism:

• History: Weight gain, central obesity, easy bruising, severe hypertension, diabetes, proximal muscle weakness, fatigue, depression, menstrual irregularities. 1
• Physical exam: Central obesity, supraclavicular fat accumulation, dorsocervical fat pad, facial plethora, wide purple striae (>1 cm), thin skin, ecchymoses, proximal muscle weakness. 1

Primary Aldosteronism Screening

Screen patients with hypertension and/or hypokalemia using aldosterone-to-renin ratio (ARR). 1, 5

• If ARR is positive, perform adrenal venous sampling (AVS) before offering adrenalectomy to determine whether aldosterone excess is unilateral (adenoma) or bilateral (hyperplasia). 1, 5
• AVS is essential because imaging alone cannot reliably lateralize aldosterone production. 5

Look for clinical features:

• History: Hypertension, hypokalemia, muscle cramping and weakness, headaches, periodic paralysis. 1
• Physical exam: Hypertension, fluid retention. 1

Pheochromocytoma Screening

Do NOT screen for pheochromocytoma if the mass shows ≤10 HU on unenhanced CT and the patient has no signs or symptoms of catecholamine excess. 1

Screen with plasma or 24-hour urinary metanephrines if:

• The mass shows >10 HU on non-contrast CT, OR
• The patient has signs/symptoms of adrenergic excess. 1

Look for clinical features:

• History: Headaches, anxiety attacks, sweating, palpitations, family history of von Hippel-Lindau disease, MEN type 2, familial paraganglioma syndrome, or neurofibromatosis type 1. 1
• Physical exam: Severe hypertension, tachycardia, arrhythmias, excessive sweating, anxiety, pallor. 1

Critical pitfall: Always exclude pheochromocytoma before any adrenal biopsy to avoid hypertensive crisis. 1

Sex Hormone Screening

Test for excess androgens only when:

• Suspected adrenocortical carcinoma, OR
• Clinical signs of virilization are present. 1

Role of Biopsy

Adrenal mass biopsy should not be performed routinely. 1

Consider biopsy only when:

• Diagnosing metastatic disease from an extra-adrenal malignancy would directly change management. 1, 8
• The patient has active extra-adrenal malignancy with a single adrenal lesion and no other sites of metastasis. 6

Never biopsy suspected ACC due to risk of tumor seeding along the needle tract. 1

Follow-Up for Non-Surgical Masses

For masses with benign imaging characteristics (≤10 HU) that are non-functional:

• No further imaging follow-up is required regardless of size. 3
• Continue annual hormonal screening for autonomous cortisol secretion for four years. 8

For indeterminate non-functional masses:

• Repeat imaging in 3-6 months using shared decision-making. 1
• If significant growth occurs, proceed to surgery. 8

Indications for Surgery

Proceed directly to adrenalectomy for:

• Unilateral cortisol-secreting mass with clinically apparent Cushing's syndrome. 1, 5
• Confirmed unilateral primary aldosteronism on AVS. 1, 5
• Pheochromocytoma (after appropriate alpha-blockade). 1
• Masses with imaging features suggesting malignancy (large size >4 cm with heterogeneity, invasion, or necrosis). 8

Consider surgery in younger patients (<40 years) with indeterminate masses due to higher malignancy risk. 3

Multidisciplinary Review

Obtain multidisciplinary input from endocrinology, surgery, and radiology when:

• Imaging is not consistent with a benign lesion
• Evidence of hormone hypersecretion exists
• The tumor has grown significantly during follow-up
• Adrenal surgery is being considered. 1