What is the management approach for a 2.5 cm adrenal nodule?

Management of a 2.5 cm Adrenal Nodule

For a 2.5 cm adrenal nodule, complete hormonal evaluation and dedicated adrenal imaging are required, with no further follow-up needed if the nodule is clearly benign (HU ≤10 on non-contrast CT) and non-functioning. 1

Initial Evaluation

Imaging Assessment

• Non-contrast CT is the first-line imaging modality
  • HU ≤10 reliably identifies benign adenomas with 0% risk of adrenocortical carcinoma 1
  • If HU >10, proceed with contrast-enhanced CT with washout protocol

    • 60% washout at 15 minutes suggests benign lesion 1

  • Chemical-shift MRI can be used as an alternative, with signal intensity loss in opposed-phase images indicating benign adenoma 1

Hormonal Evaluation

All adrenal nodules require complete hormonal assessment regardless of size:

1. Cortisol assessment:

   • 1mg overnight dexamethasone suppression test (cutoff value ≤50 nmol/L or ≤1.8 µg/dL) 1, 2

2. Catecholamine assessment:

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

3. Aldosterone assessment (in patients with hypertension/hypokalemia):

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

Management Based on Imaging Characteristics

Benign-appearing adenoma (<4 cm)

• If clearly benign on imaging (HU ≤10) and non-functioning:
  • No further follow-up imaging or functional testing required 1

Indeterminate adenoma (2.5 cm)

• If HU >10 but <4 cm with no aggressive features:
  • Repeat imaging in 6-12 months 3
  • If unchanged, no further follow-up needed
  • If enlarging (>1 cm in 1 year), consider adrenalectomy 3

Management Based on Hormonal Status

Non-functioning adenoma

• For a 2.5 cm non-functioning adenoma with benign imaging features:
  • No surgical intervention indicated 2

Mild Autonomous Cortisol Secretion (MACS)

• If post-dexamethasone cortisol >50 nmol/L (>1.8 µg/dL) without overt Cushing's syndrome:
  • Screen for cortisol-related comorbidities (hypertension, type 2 diabetes)
  • Consider surgery if comorbidities are present and potentially related to cortisol excess 2

Functioning adenoma

• Pheochromocytoma: Surgical resection with preoperative alpha-blockade 1
• Aldosterone-producing adenoma: Laparoscopic adrenalectomy if unilateral 3
• Cortisol-producing adenoma: Laparoscopic adrenalectomy 3

Surgical Considerations

• Minimally invasive surgery (laparoscopic approach) is preferred for benign 2.5 cm adenomas 1
• Open adrenalectomy is considered for tumors with features concerning for malignancy 1

Follow-up for Non-operated Patients

• For non-functioning, benign-appearing 2.5 cm adenomas:
  • No further imaging follow-up needed if clearly benign (HU ≤10) 1
  • If indeterminate features, repeat imaging in 6-12 months 3
  • Consider repeat hormonal screening at 1-2 years 1

Important Caveats

• Malignancy should be suspected if the tumor has irregular morphology, is lipid-poor, does not wash out on contrast-enhanced CT, or is secreting more than one hormone 3
• While the 2.5 cm size is below the 3-4 cm threshold that raises concern for malignancy, hormonal functionality must still be ruled out 3, 1
• Adrenal vein sampling may be necessary to distinguish unilateral adenoma from bilateral hyperplasia in cases of hyperaldosteronism 3

By following this systematic approach to evaluation and management, the appropriate treatment strategy for a 2.5 cm adrenal nodule can be determined based on imaging characteristics and hormonal status.