What is the initial evaluation and laboratory work-up for an adrenal mass?

Adrenal Mass Differential Diagnosis and Laboratory Work-Up

Differential Diagnosis

Adrenal masses are categorized into three groups: benign non-functional lesions, benign hyperfunctioning lesions, and malignant lesions. 1

Benign Non-Functional Lesions

• Adenomas (most common, representing the majority of incidentalomas) 1
• Myelolipomas (contain macroscopic fat) 2
• Adrenal cysts 3
• Hemorrhage 4

Benign Hyperfunctioning Lesions

• Cortisol-secreting adenomas (5.3% of incidentalomas) 1, 2
• Aldosterone-secreting adenomas (1% of incidentalomas) 1, 2
• Pheochromocytomas (5.1% of incidentalomas) 1, 2

Malignant Lesions

• Adrenocortical carcinoma (4.7% of incidentalomas) 1
• Metastases (2.5% of incidentalomas, but up to 50% in patients with known extra-adrenal malignancy) 1, 5

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Laboratory Work-Up Algorithm

All patients with adrenal incidentalomas ≥1 cm require biochemical screening for hormone excess, regardless of imaging characteristics or symptoms. 1, 2, 6

Step 1: Universal Screening (All Patients)

1 mg Overnight Dexamethasone Suppression Test (mandatory for all patients) 2, 7

• Administer 1 mg dexamethasone at 11 PM
• Measure serum cortisol at 8 AM the next morning
• Interpretation:
  • ≤50 nmol/L (1.8 μg/dL): Excludes autonomous cortisol secretion 2, 7
  • 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion 2, 7

  • 138 nmol/L (>5.0 μg/dL): Evidence of autonomous cortisol secretion 2, 7

Step 2: Conditional Testing Based on Clinical Features

Pheochromocytoma Screening (perform if ANY of the following):

• Adrenal mass ≥10 HU on non-contrast CT 2, 6
• Symptoms of catecholamine excess (hypertension, headaches, palpitations, diaphoresis) 2
• Testing options:
  • Plasma free metanephrines (preferred) 2
  • 24-hour urinary metanephrines and normetanephrines 2
• Critical pitfall: Must exclude pheochromocytoma before any biopsy to avoid hypertensive crisis 7, 6

Primary Aldosteronism Screening (perform if):

• Hypertension present 2
• Hypokalemia present 2
• Test: Aldosterone/renin ratio
  • Ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity 2

Androgen Testing (perform if):

• Suspected adrenocortical carcinoma (large mass, suspicious imaging) 2
• Clinical signs of virilization or feminization 2, 7
• Tests: DHEAS, testosterone, 17-hydroxyprogesterone, androstenedione, estradiol 2

Step 3: Special Considerations

Bilateral Adrenal Masses:

• Evaluate each lesion separately using the same protocol 2, 4
• Add: Serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 2, 4

Patients with Known Extra-Adrenal Malignancy:

• Still perform full hormonal evaluation—up to 50% will have primary adrenal pathology rather than metastases 5
• Do not assume metastatic disease without biochemical exclusion of functional tumors 5

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History and Physical Examination Targets

Focus on identifying signs/symptoms of hormone excess and malignancy: 1

Cortisol Excess

• Weight gain, central obesity, moon facies, buffalo hump 1
• Purple striae, easy bruising, proximal muscle weakness 1
• Hypertension, diabetes, osteoporosis 1

Aldosterone Excess

• Resistant hypertension 2
• Hypokalemia (spontaneous or diuretic-induced) 2
• Muscle weakness, cramping 2

Catecholamine Excess

• Episodic or sustained hypertension 2
• Headaches, palpitations, diaphoresis (classic triad) 2
• Anxiety, tremor, pallor 2

Androgen/Estrogen Excess

• Virilization in women (hirsutism, deepening voice, clitoromegaly) 2
• Feminization in men (gynecomastia, testicular atrophy) 2

Malignancy Features

• Rapid growth, abdominal/flank pain 1
• Weight loss, constitutional symptoms 1
• History of extra-adrenal malignancy 5

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Medication Interference Considerations

Hold interfering medications before testing when possible: 2

• Beta-blockers, ACE inhibitors, ARBs affect aldosterone/renin ratio
• Tricyclic antidepressants, decongestants affect metanephrine testing
• Estrogen, rifampin affect cortisol testing

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When to Involve Multidisciplinary Team

Low threshold for consultation with endocrinology, surgery, and radiology when: 1

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

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Follow-Up Hormonal Testing

Benign non-functional adenomas <4 cm, myelolipomas, and masses with macroscopic fat: No repeat functional testing required 2

Indeterminate masses with growth >5 mm/year: Repeat full functional work-up before considering surgery 2

Masses with growth <3 mm/year: No further functional testing needed 2