What is the recommended workup for an adrenal adenoma?

Adrenal Adenoma Workup

The recommended workup for an adrenal adenoma should include a focused history and physical examination, non-contrast CT as first-line imaging, and comprehensive hormonal evaluation for all patients, with second-line imaging reserved for indeterminate lesions. 1

Initial Assessment

History and Physical Examination

• Focus on identifying:
  • Signs/symptoms of hormone excess (weight gain, hypertension, hirsutism, muscle weakness)
  • Features suggesting malignancy (rapid weight loss, pain)
  • Symptoms of catecholamine excess (palpitations, headaches, sweating)
  • History of extra-adrenal malignancy 1

First-Line Imaging

• Non-contrast CT is the preferred initial imaging modality
  • Hounsfield units (HU) < 10 reliably indicate benign adenoma
  • Risk of adrenocortical carcinoma is 0% when HU < 10,0.5% when HU 10-20, and 6.3% when HU > 20 1
  • Evaluate size, homogeneity, margins, and presence of calcifications 2

Hormonal Evaluation

Required for All Patients

1. Cortisol secretion assessment:

   • 1mg overnight dexamethasone suppression test (preferred screening test)
   • Cortisol ≤ 50 nmol/L (≤1.8 µg/dL) indicates normal suppression 3
   • Consider additional testing (24-hour urinary free cortisol, late-night salivary cortisol) if results are equivocal 1

2. Pheochromocytoma screening:

   • Plasma or 24-hour urinary metanephrines
   • Can be omitted only in patients with unequivocal adrenocortical adenomas (HU < 10) without symptoms of catecholamine excess 1

Selective Testing Based on Clinical Features

1. Primary aldosteronism screening:

   • Aldosterone-to-renin ratio in patients with hypertension and/or hypokalemia 1
   • If positive, adrenal vein sampling is recommended before considering adrenalectomy 1

2. Sex hormone and steroid precursor assessment:

   • DHEA-S, 17-OH-progesterone, androstenedione, testosterone
   • Indicated when adrenocortical carcinoma is suspected or virilization is present 1

Second-Line Imaging (for Indeterminate Lesions)

• Contrast-enhanced CT with washout protocol:

  • 60% washout at 15 minutes suggests benign lesion 2

  • OR
• Chemical-shift MRI:
  • Signal intensity loss in opposed-phase images indicates benign adenoma 2

Management Decision Algorithm

Surgical Intervention Indicated For:

1. Lesions with radiologic features concerning for malignancy:

   • Size >4 cm
   • Irregular margins
   • Heterogeneous appearance
   • HU >20 on non-contrast CT
   • Growth >5 mm/year on follow-up imaging 1

2. Hormone-producing adenomas:

   • Unilateral cortisol-secreting masses with Cushing's syndrome
   • Aldosterone-secreting adenomas (after confirming lateralization)
   • Pheochromocytomas 1

3. Younger patients with mild autonomous cortisol secretion and progressive metabolic comorbidities 1

Follow-up for Non-Surgical Cases:

• Benign non-functional adenomas <4 cm (HU <10):

  • No further imaging or functional testing required 1

• Non-functional adenomas ≥4 cm with benign radiologic features:

  • Repeat imaging in 6-12 months 1

• Indeterminate non-functional lesions:

  • Repeat imaging in 3-6 months 1
  • If growth <3 mm/year, no further imaging needed
  • If growth >5 mm/year, repeat functional workup and consider surgery 1

Important Caveats and Pitfalls

1. Avoid adrenal mass biopsy as it is rarely indicated and contraindicated when pheochromocytoma has not been excluded or adrenocortical carcinoma is suspected (risk of tumor seeding) 1, 2

2. Don't rely solely on imaging size for surgical decisions; functional status and imaging characteristics are equally important 1

3. Consider multidisciplinary review when:

   • Imaging is not consistent with a benign lesion
   • Evidence of hormone hypersecretion exists
   • Significant tumor growth is observed
   • Surgery is being considered 1

4. Beware of false negatives in hormonal testing, particularly in subclinical Cushing's syndrome, which may require multiple tests for accurate diagnosis 4

5. Don't delay workup as adrenocortical carcinoma has poor prognosis when diagnosed late 2