What is the appropriate workup for a suspected adrenal adenoma?

Workup for Adrenal Adenoma

The appropriate workup for a suspected adrenal adenoma must include both imaging characterization and comprehensive hormonal evaluation, regardless of whether the mass is symptomatic or incidentally discovered. 1

Initial Evaluation

Focused History and Physical Examination

• Target specific signs and symptoms of hormone excess:
  • Hypercortisolism: Weight gain, central obesity, easy bruising, hypertension, diabetes, proximal muscle weakness, fatigue, depression, sleep disturbances, menstrual irregularities 1
  • Primary aldosteronism: Hypertension, hypokalemia, muscle cramping, weakness, headaches 1
  • Pheochromocytoma: Headaches, anxiety attacks, sweating, palpitations, family history of related syndromes 1
  • Adrenocortical carcinoma: Flank pain, abdominal discomfort, rapid onset of hypercortisolism, virilization 1
  • Metastasis: History of malignancy, weight loss, unexplained fevers 1

Imaging Evaluation

1. Non-contrast CT as first-line imaging 1

   • Homogeneous lesions with HU ≤10 are benign regardless of size
   • HU >10 requires further evaluation

2. Second-line imaging for indeterminate masses 1

   • Washout CT or chemical-shift MRI

   • 60% washout in 15 minutes suggests benign nature

3. Size considerations:

   • <4 cm with benign features: likely benign
   • 4-6 cm: intermediate risk

   • 6 cm: high risk of malignancy 1

Hormonal Evaluation

Mandatory for ALL adrenal incidentalomas:

1. Cortisol secretion 1

   • 1 mg overnight dexamethasone suppression test (DST)
   • Interpretation:
     • ≤50 nmol/L (≤1.8 μg/dL): excludes hypersecretion
     • 51-138 nmol/L: possible autonomous cortisol secretion

     • 138 nmol/L: evidence of cortisol hypersecretion

   • Additional tests if abnormal: ACTH level, 24-hour urinary free cortisol

2. For patients with hypertension and/or hypokalemia:

   • Aldosterone/renin ratio (ARR) 1
     • Collect in morning after patient has been upright for 2 hours and seated for 5-15 minutes
     • Ensure patient is potassium-replete and off interfering medications
     • ARR >20 ng/dL per ng/mL/hr has >90% sensitivity/specificity for hyperaldosteronism
   • If positive, adrenal vein sampling is recommended before surgery 1

3. For masses with HU >10 or symptoms of catecholamine excess:

   • Plasma free metanephrines or 24-hour urinary metanephrines 1

   • 2x upper limit of normal is diagnostic

4. For suspected adrenocortical carcinoma or virilization:

   • DHEAS, testosterone 1
   • Consider additional androgens if clinically indicated

Management Algorithm

1. Functional adenomas:

   • Cortisol-secreting adenomas with overt Cushing's syndrome: adrenalectomy 1
   • Aldosterone-secreting adenomas: adrenalectomy after confirming unilateral production 1
   • Pheochromocytoma: adrenalectomy 1

2. Non-functional adenomas:

   • <4 cm with benign features: no further follow-up needed 1
   • ≥4 cm with benign features (<10 HU): repeat imaging in 6-12 months 1
   • Growth >5 mm/year: consider adrenalectomy after repeating functional workup 1
   • Growth <3 mm/year: no further follow-up needed 1

3. Indeterminate masses:

   • Consider repeat imaging in 3-6 months versus surgical resection 1

Common Pitfalls to Avoid

1. Biopsy: Adrenal mass biopsy should not be performed routinely 1

   • Only consider if metastatic disease is suspected and would change management
   • Always exclude pheochromocytoma before biopsy

2. Inadequate hormone testing: Missing subclinical hormone excess can lead to perioperative complications

   • All patients need cortisol evaluation regardless of symptoms 1
   • Mild autonomous cortisol secretion is associated with increased morbidity 2

3. Over-reliance on size alone: While size is important, imaging characteristics and hormone status are equally crucial for management decisions 1

4. Inadequate follow-up: Non-functional adenomas may develop hormone excess over time, particularly in larger masses 1

5. Missing bilateral disease: In primary aldosteronism, adrenal vein sampling is essential to distinguish unilateral from bilateral disease before surgery 1, 3