What is the recommended workup for a patient with an adrenal nodule?

Workup for Adrenal Nodules

All patients with adrenal nodules should undergo both comprehensive imaging and hormonal evaluation to rule out malignancy and hormone excess, regardless of how the nodule was discovered. 1, 2

Initial Evaluation

Imaging Assessment

• CT scan of abdomen (non-contrast and contrast-enhanced) is the first-line imaging test
  • Hounsfield units (HU) ≤10 on non-contrast CT indicates benign adenoma with 0% risk of adrenocortical carcinoma 2
  • Contrast washout >60% at 15 minutes suggests benign lesion 2
  • MRI with chemical-shift imaging can be used if CT is contraindicated

Risk Stratification Based on Imaging

1. Low risk of malignancy:

   • Homogeneous lesions with HU ≤10 on unenhanced CT (benign regardless of size) 3
   • No additional imaging required for these lesions

2. High risk of malignancy:

   • Lesions >4 cm with inhomogeneous appearance or HU >20
   • All masses >6 cm regardless of appearance
   • Irregular margins, poor contrast washout (<60% at 15 minutes)
   • Growth >5 mm/year on follow-up imaging

Hormonal Evaluation

All patients with adrenal nodules require comprehensive hormonal evaluation regardless of imaging characteristics 1, 2:

1. Cortisol secretion (required for all patients):

   • 1-mg overnight dexamethasone suppression test (DST)
   • Interpretation:
     • ≤50 nmol/L (≤1.8 μg/dL): excludes cortisol hypersecretion
     • 51-138 nmol/L (1.9-5.0 μg/dL): possible autonomous cortisol secretion

     • 138 nmol/L (>5.0 μg/dL): evidence of cortisol hypersecretion 2, 3

2. Catecholamine excess (required for all patients):

   • Plasma free metanephrines or 24-hour urinary fractionated metanephrines
   • Values >2× upper limit of normal strongly suggest pheochromocytoma 1, 2

3. Aldosterone excess (for patients with hypertension and/or hypokalemia):

   • Aldosterone-to-renin ratio (ARR)
   • ARR >20 ng/dL per ng/mL/hr has >90% sensitivity/specificity for hyperaldosteronism 1

4. Sex hormone evaluation (for suspected adrenocortical carcinoma or virilization):

   • DHEAS, testosterone
   • Consider 17β-estradiol, 17-OH progesterone, androstenedione in selected cases 1

Additional Workup Based on Initial Findings

For Suspected Malignancy

• Chest CT to evaluate for metastatic disease 1
• Consider FDG-PET/CT for suspected metastatic disease 2
• Bone scintigraphy if skeletal metastases are suspected 1

For Hormone-Producing Tumors

• Cortisol excess: Additional testing may include ACTH levels, 24-hour urinary free cortisol, midnight salivary cortisol 1
• Aldosterone excess: Confirmatory testing with saline suppression or salt loading with 24-hour urine aldosterone measurement 1
• Pheochromocytoma: Consider MIBG scintigraphy, DOTA-TATE-PET, or Dopa/Dopamine PET 1

Management Recommendations

Surgical Intervention is Indicated for:

• Masses >4 cm with inhomogeneous appearance or HU >20 1
• All masses >6 cm regardless of appearance 1
• Biochemically confirmed pheochromocytomas 2
• Aldosterone-secreting adenomas 2
• Cortisol-secreting adenomas 2
• Growth >5 mm/year on follow-up imaging 2

Follow-up for Non-Operated Patients

• Benign-appearing adenomas <4 cm with HU ≤10: no further follow-up imaging or functional testing required 2
• Benign-appearing adenomas ≥4 cm: repeat imaging in 6-12 months 2
• For non-operated patients with non-functioning masses: consider repeat screening for pheochromocytoma and hypercortisolism at 1-2 years 2

Common Pitfalls to Avoid

• Failure to perform hormonal evaluation even for radiologically benign-appearing lesions
• Performing adrenal biopsy, which is generally not recommended for suspected adrenocortical carcinoma 2
• Inadequate preoperative preparation for pheochromocytoma (requires alpha-blockade followed by beta-blockade)
• Overlooking mild autonomous cortisol secretion, which is associated with increased cardiovascular morbidity 3