What is the workup for a 2 cm adrenal adenoma found on a computed tomography (CT) scan?

Workup for a 2 cm Adrenal Adenoma

All patients with a 2 cm adrenal adenoma require comprehensive hormonal screening regardless of symptoms or imaging characteristics, combined with radiological characterization to determine if the lesion is benign. 1, 2

Initial Radiological Evaluation

Obtain non-contrast CT imaging to measure Hounsfield units (HU):

• If the lesion measures ≤10 HU on unenhanced CT, it is a benign lipid-rich adenoma requiring no further imaging 1, 2, 3
• If HU >10, proceed with either washout CT or chemical shift MRI to further characterize the mass 1, 2
• For washout CT: >60% absolute washout or >40% relative washout at 15 minutes indicates benign adenoma 2
• For chemical shift MRI: homogeneous signal intensity drop indicates lipid-rich adenoma 1

Important caveat: Approximately one-third of pheochromocytomas can demonstrate washout characteristics similar to adenomas, and one-third of adenomas may not washout in the typical benign range, so imaging alone is insufficient—hormonal testing is mandatory. 1

Mandatory Hormonal Screening

All patients require the following tests regardless of symptoms: 1, 2, 4

1. Screen for Autonomous Cortisol Secretion

• Perform 1 mg overnight dexamethasone suppression test (give 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM) 2, 4
• Cortisol ≤50 nmol/L (≤1.8 μg/dL) excludes hypersecretion 2, 4, 3
• Cortisol 51-138 nmol/L (1.9-5.0 μg/dL) indicates mild autonomous cortisol secretion (MACS) 2, 3
• Cortisol >138 nmol/L (>5.0 μg/dL) indicates overt hypersecretion 2, 3

2. Screen for Pheochromocytoma

• Measure plasma free metanephrines or 24-hour urinary fractionated metanephrines/normetanephrines 1, 2, 4
• This testing is critical before any surgical intervention to prevent hypertensive crisis 1, 5
• Must be performed even if imaging suggests benign adenoma 2

3. Screen for Primary Aldosteronism (if hypertension or hypokalemia present)

• Measure aldosterone-to-renin ratio 1, 2, 4
• Ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for hyperaldosteronism 2, 4
• Testing recommended for all hypertensive patients with adrenal masses 1

4. Screen for Sex Hormone Excess (only if clinical signs present)

• Measure DHEAS, testosterone, androstenedione, 17-hydroxyprogesterone only if virilization or feminization signs present 2, 4
• Not routinely indicated for asymptomatic 2 cm masses 4

Clinical Assessment

Perform focused history and physical examination looking for: 1, 2

• Cushing's syndrome features: Central obesity, moon face, buffalo hump, purple striae >1 cm, easy bruising, proximal muscle weakness, hypertension, diabetes, osteoporosis 1, 2
• Pheochromocytoma symptoms: Episodic headaches, palpitations, diaphoresis, anxiety attacks, family history of MEN2, von Hippel-Lindau, neurofibromatosis 1
• Hyperaldosteronism features: Resistant hypertension, hypokalemia, muscle weakness and cramping 1, 2

Management Based on Results

If Nonfunctioning and Benign Imaging Features (<10 HU)

• No surgery indicated 1, 4
• Repeat imaging in 12 months 1
• Repeat hormonal screening (dexamethasone suppression test and metanephrines only) annually for 4 years if lesion >3 cm 1
• No further follow-up needed if stable at 12 months and <2 cm 1

If Functioning (Any Hormonal Excess)

• Surgical resection indicated (laparoscopic adrenalectomy preferred) 1, 4
• For unilateral aldosterone production: consider adrenal vein sampling in patients >40 years to confirm lateralization 1

If Indeterminate Imaging

• Repeat imaging in 3-6 months or consider surgical resection based on shared decision-making 1, 4
• Adrenalectomy should be considered if growth >5 mm/year after repeating functional workup 1, 5

Critical Pitfalls to Avoid

• Never biopsy an adrenal mass before excluding pheochromocytoma—this can precipitate fatal hypertensive crisis 1
• Do not rely on imaging characteristics alone—5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment 5
• Do not skip hormonal screening based on lesion size—even small lesions can be functional 1, 2
• Medications can interfere with hormone testing—consider holding interfering medications when possible 4
• For patients with MACS (cortisol 51-138 nmol/L post-dexamethasone), screen for and aggressively treat metabolic comorbidities (hypertension, diabetes, osteoporosis) as these patients have increased morbidity and mortality 3