What is the diagnostic approach for a patient suspected of having an adrenal tumor?

Diagnostic Approach for Adrenal Tumors

All patients with an adrenal lesion ≥1 cm require comprehensive biochemical screening for hormone excess combined with non-contrast CT imaging as the initial diagnostic workup, regardless of imaging characteristics or symptoms. 1

Mandatory Hormonal Testing for Every Patient

Perform a 1 mg overnight dexamethasone suppression test in every patient with an adrenal tumor ≥1 cm. 1, 2 This test is interpreted as follows: 1

• ≤50 nmol/L (1.8 μg/dL): Excludes autonomous cortisol secretion
• 51-138 nmol/L (1.9-5.0 μg/dL): Suggests possible autonomous cortisol secretion
• >138 nmol/L (>5.0 μg/dL): Confirms autonomous cortisol secretion

Measure plasma ACTH levels as part of the cortisol assessment. 3

Conditional Hormonal Testing Based on Specific Features

Screen for pheochromocytoma using plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines if: 1, 3

• The adrenal mass measures ≥10 Hounsfield Units (HU) on non-contrast CT, OR
• Any symptoms of catecholamine excess are present (hypertension, heart palpitations, headaches, excessive sweating, anxiety)

This testing has 97% sensitivity and 91% specificity. 1

Screen for primary aldosteronism using aldosterone-to-renin ratio if: 1, 3

• The patient has hypertension and/or hypokalemia
• A ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for hyperaldosteronism

Also measure serum potassium levels in these patients. 3

Test for androgen excess (DHEA-S, 17-OH-progesterone, androstenedione, 17-beta-estradiol) only if: 3

• Virilization or feminization is present clinically
• Adrenocortical carcinoma is suspected based on imaging

First-Line Imaging Protocol

Obtain non-contrast CT as the first-line imaging test. 1 The attenuation value on non-contrast CT is critical for characterization: 1, 4

• <10 HU: Lipid-rich adenoma (71% sensitivity, 98% specificity) - no further imaging characterization needed
• ≥10 HU: Indeterminate mass requiring second-line imaging

For indeterminate masses (≥10 HU on non-contrast CT), obtain either washout CT or chemical shift MRI. 5 However, be aware of important limitations: 5

• Approximately 1/3 of pheochromocytomas may washout in the characteristic range of an adenoma
• Approximately 1/3 of adrenal adenomas do not washout in the adenoma range
• Malignant masses can also washout in the adenoma range

Chemical shift MRI detects microscopic fat through signal intensity drop, which is diagnostic of lipid-rich adenoma when homogeneous. 5

Targeted History and Physical Examination

Look for cortisol excess signs: 1

• Weight gain, central obesity, moon facies, buffalo hump (dorsocervical fat pad)
• Purple striae (>1 cm wide), easy bruising, thinned skin
• Proximal muscle weakness, facial plethora, supraclavicular fat accumulation
• Hypertension, diabetes, fragility fractures
• Present in 50-70% of patients with Cushing's syndrome

Look for aldosterone excess signs: 1

• Resistant hypertension, hypokalemia
• Muscle weakness and cramping
• Present in 50-70% of patients with primary aldosteronism

Look for pheochromocytoma signs: 6

• Episodic hypertension, heart palpitations, headaches
• Excessive perspiration, nervousness, anxiety or panic attacks

Look for adrenocortical carcinoma signs: 6

• Abdominal pain or feeling of fullness from mass effect
• Unexplained weight gain or loss, weakness
• Virilization or feminization features

Role of Adrenal Biopsy

Do not perform adrenal biopsy routinely. 1, 2 Biopsy is only considered when: 5, 1

• Diagnosis of metastatic disease from an extra-adrenal malignancy would change management
• The patient has a known history of extra-adrenal cancer

Critical safety requirement: Always exclude pheochromocytoma before any biopsy attempt to avoid precipitating a life-threatening hypertensive crisis. 1, 2, 3

Do not biopsy suspected adrenocortical carcinoma due to risk of tumor seeding along the needle tract. 5

Common Diagnostic Pitfalls to Avoid

Do not skip dexamethasone suppression testing even in small, benign-appearing masses - autonomous cortisol secretion is present in 5.3% of incidentalomas. 1, 2

Do not screen for pheochromocytoma in patients with confirmed lipid-rich adenomas (<10 HU) who lack symptoms - the risk is low in this population. 1

Do not rely solely on imaging to distinguish benign from malignant tumors - radiological appearance cannot reliably predict hormone secretion status or exclude malignancy in all cases. 3, 6

Do not perform routine androgen testing unless virilization, feminization, or suspected adrenocortical carcinoma is present - the yield is low in asymptomatic patients. 1

Differential Diagnosis Considerations

The most common adrenal tumors by prevalence are: 5

• Nonfunctioning adenoma: 71-84%
• Myelolipoma: 7-15%
• Cysts: 4-22%
• Cortisol-secreting adenoma: 1-30%
• Aldosterone-secreting adenoma: 2-7%
• Pheochromocytoma: 1.5-14%
• Adrenocortical carcinoma: 1.2-12%
• Metastases: 0-21%