What is the workup for a patient with an adrenal adenoma?

Workup for Adrenal Adenoma

The workup for a patient with an adrenal adenoma should include a focused history and physical examination, comprehensive hormonal evaluation, and appropriate imaging studies to determine if the mass is benign or malignant and if it is hormonally active or non-functional. 1, 2

Initial Evaluation

History and Physical Examination

• Focus on identifying signs/symptoms of:
  • Cortisol excess: weight gain, central obesity, facial rounding, purple striae, buffalo hump, proximal muscle weakness, easy bruising, hypertension, glucose intolerance, mood changes 2
  • Aldosterone excess: hypertension, hypokalemia, muscle weakness, headaches, polyuria, polydipsia 2
  • Catecholamine excess: episodic or persistent hypertension, headaches, palpitations, profuse sweating, pallor, anxiety, tremors, weight loss 2
  • Androgen excess: hirsutism, virilization, menstrual irregularities in females 2
  • Malignancy: abdominal or flank pain, palpable mass, weight loss, early satiety, fever, night sweats 2

Hormonal Evaluation

All patients with adrenal adenomas should undergo the following hormonal tests regardless of imaging appearance 2:

1. Cortisol evaluation:

   • 1mg overnight dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 µg/dL indicates normal suppression) 2, 3

2. Catecholamine evaluation:

   • Plasma-free or 24-hour urinary fractionated metanephrines 2

3. Aldosterone evaluation:

   • Aldosterone-to-renin ratio (for hypertensive patients) 2

Imaging Evaluation

First-line Imaging

• Non-contrast CT is the recommended initial imaging modality 1, 2
  • Hounsfield Units (HU) ≤10 indicates a benign adenoma with 0% risk of adrenocortical carcinoma 1, 2
  • Homogeneous, well-circumscribed appearance supports benign etiology 1

Second-line Imaging (for indeterminate lesions)

• Contrast-enhanced CT washout study:

  • 60% washout at 15 minutes suggests benign lesion 2

  • Sensitivity >95% and specificity >97% for adenoma detection 2

• Chemical-shift MRI:

  • Signal intensity loss in opposed-phase images indicates benign adenoma 2
  • Useful when patient has contraindication to CT contrast 2

• FDG-PET:

  • Consider for radiologically indeterminate cases 2
  • High tracer uptake suggests malignancy 2

Risk Stratification Based on Imaging and Size

• Low risk of malignancy:

  • Homogeneous lesions with HU ≤10 on unenhanced CT (benign regardless of size) 3
  • Small (<3 cm), non-functioning, benign-appearing lesions 2

• Intermediate risk:

  • Lesions with HU 10-20 (0.5% risk of adrenocortical carcinoma) 1
  • Indeterminate washout on contrast CT

• High risk of malignancy:

  • Lesions >4 cm that are inhomogeneous or have HU >20 3
  • Irregular margins and enhancement after contrast media 4
  • HU >20 (6.3% risk of adrenocortical carcinoma) 1

Management Considerations

• Multidisciplinary review is recommended when:

  • Imaging is not consistent with a benign lesion
  • There is evidence of hormone hypersecretion
  • The tumor has grown significantly during follow-up
  • Adrenal surgery is being considered 1, 2

• Approximately 20% of adrenal incidentalomas require surgical intervention 2

Common Pitfalls to Avoid

1. Missing functional tumors: Up to 19.4% of incidentalomas may secrete excess cortisol, often without overt clinical signs of Cushing's syndrome 5

2. Relying solely on size: While size correlates with malignancy risk (lesions <3 cm are usually benign, >6 cm have high malignancy risk), imaging characteristics are equally important 4

3. Inadequate hormonal evaluation: Even apparently asymptomatic patients may have clinically significant hormone excess 2, 5

4. Failure to recognize mild autonomous cortisol secretion (MACS): Patients with cortisol levels >50 nmol/L (>1.8 µg/dL) after dexamethasone suppression may have increased morbidity and mortality risk even without overt Cushing's syndrome 3

5. Inadequate follow-up: Non-operated patients with indeterminate lesions require repeat evaluation for growth after 3-12 months 2