What is the recommended management for an adrenal nodule?

Management of Adrenal Nodules: A Comprehensive Approach

The management of adrenal nodules should follow a structured algorithm based on imaging characteristics, hormonal evaluation, and size, with surgical intervention recommended for nodules that are >4 cm, have suspicious imaging features, or demonstrate hormonal hypersecretion. 1

Initial Evaluation

Imaging Assessment

• First-line imaging: Non-contrast CT is the recommended initial imaging modality 1

  • HU ≤10: Reliably indicates benign adenoma
  • HU 10-20: Indicates low risk of malignancy
  • HU >20: Indicates higher risk of malignancy
  • Size ≥4 cm: Higher risk of malignancy regardless of HU

• Second-line imaging (if needed):

  • Contrast-enhanced CT: >60% washout at 15 minutes suggests benign lesion
  • Chemical-shift MRI: Signal intensity loss in opposed-phase images indicates benign adenoma

Hormonal Evaluation

All adrenal nodules require hormonal evaluation regardless of size 1, 2:

• 1mg overnight dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 μg/dL excludes autonomous cortisol secretion)
• Plasma or 24-hour urinary metanephrines (for pheochromocytoma)
• Aldosterone-to-renin ratio (for primary aldosteronism)
• Consider sex hormones (DHEA-S, 17-OH-progesterone, androstenedione, testosterone) if adrenocortical carcinoma suspected

Management Algorithm Based on Imaging and Functional Status

1. Benign-appearing, Non-functional Nodules (<10 HU on non-contrast CT)

• <4 cm: No further follow-up imaging or functional testing required 3, 1
• ≥4 cm: Repeat imaging in 6-12 months 3
  • If growth <3 mm/year: No further imaging or functional testing required
  • If growth >5 mm/year: Consider adrenalectomy after repeating functional work-up

2. Indeterminate Non-functional Nodules (>10 HU or heterogeneous)

• <4 cm: Repeat imaging in 3-6 months 3
• ≥4 cm: Consider surgical resection or repeat imaging in 3-6 months based on shared decision-making 3
• >6 cm: Surgical resection recommended due to increased risk of malignancy 1

3. Functional Nodules (regardless of imaging characteristics)

• Pheochromocytoma: Surgical resection after appropriate alpha-blockade (1-3 weeks preoperatively) 3, 1
• Cortisol-secreting adenoma: Consider adrenalectomy, especially with cortisol-related comorbidities 3, 1, 2
• Aldosterone-producing adenoma: Adrenalectomy for unilateral aldosterone production 3, 1

4. Suspicious for Malignancy

• Imaging features: Large size (>4 cm), heterogeneity, evidence of invasion or necrosis
• Recommendation: Surgical resection 3, 1
  • Tumors >5-6 cm: Open adrenalectomy preferred
  • Tumors <5 cm without invasion: Laparoscopic adrenalectomy acceptable

Special Considerations

Bilateral Adrenal Nodules

• Evaluate each nodule individually using the same criteria as unilateral nodules 3
• Measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 3
• Assess for adrenal insufficiency in suspected bilateral infiltrative disease, metastases, or hemorrhage 3
• Avoid bilateral adrenalectomy for asymptomatic cortisol-secreting adenomas 3

High-Risk Populations

• Young adults, children, pregnant patients: Expedite evaluation due to higher risk of malignancy 3
• Consider MRI instead of CT to reduce radiation exposure 3

Adrenal Biopsy

• Rarely indicated and should not be routinely performed 1
• Consider only when:
  • Suspicion of metastatic disease from known primary malignancy
  • Pathology results would directly change management
  • Pheochromocytoma has been excluded
  • Primary adrenal malignancy is not suspected (risk of tumor seeding) 3

Follow-up Recommendations

• Benign, non-functional nodules <4 cm: No follow-up needed 3, 1
• Benign, non-functional nodules ≥4 cm: Repeat imaging in 6-12 months 3
• Indeterminate nodules under observation: Repeat imaging in 3-6 months 3
• Post-surgical patients: Clinical, imaging, and biochemical screens for at least 10 years 1

Common Pitfalls to Avoid

• Failure to exclude pheochromocytoma before any invasive procedure (including biopsy)
• Delaying evaluation of suspicious nodules in young patients
• Performing unnecessary biopsies of adrenal masses
• Missing mild autonomous cortisol secretion (MACS) which can contribute to metabolic complications
• Using minimally invasive approaches for suspected adrenocortical carcinoma (risk of tumor seeding and recurrence) 3

By following this structured approach to adrenal nodule management, clinicians can effectively identify and treat clinically significant adrenal pathology while avoiding unnecessary interventions for benign, non-functional lesions.