What is the recommended management approach for adrenal nodules?

Management of Adrenal Nodules

For adrenal incidentalomas, initial evaluation should include unenhanced CT and hormone screening, followed by a structured management approach based on imaging characteristics and functional status. 1

Initial Evaluation

Imaging Assessment

• Every patient with an adrenal incidentaloma should receive an unenhanced CT if not already performed 1
• Adrenal masses should be assessed as benign or indeterminate based on:
  • Lesion density (≤10 HU suggests benign adenoma) 1
  • Size (>4 cm increases risk of malignancy) 1
• If initial unenhanced CT is equivocal, proceed to enhanced CT with washout (absolute percent washout-to-relative percent washout of 60%:40% or less suggests benign pathology) 1
• MRI is appropriate for high-risk populations (pregnant women, people <40 years old) 1
• PET can be useful in patients with history of malignancy 1

Hormonal Evaluation

• All patients require initial hormonal testing including: 1
  • Low-dose dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 µg/dL indicates normal suppression) 2
  • Plasma-free and/or urinary fractionated metanephrines to rule out pheochromocytoma 1
  • Aldosterone-to-renin ratio only if patients have unexplained hypokalemia or hypertension 1
• For suspected adrenocortical carcinoma, include levels of sex hormones and steroid precursors 1

Management Algorithm

For Benign-Appearing, Non-Functioning Adrenal Masses (<4 cm, ≤10 HU)

• No further follow-up imaging or functional testing required 1
• Exception: For masses ≥4 cm that appear radiologically benign (<10 HU), repeat imaging in 6-12 months 1

For Benign-Appearing Masses with Growth

• Adrenalectomy should be considered for adrenal incidentalomas growing >5 mm/year (after repeating functional work-up) 1
• No further imaging follow-up or functional testing required for lesions growing <3 mm/year 1

For Indeterminate Non-Functioning Lesions

• Management options include repeat imaging in 3-12 months versus surgical resection 1
• The timeframe for repeat imaging (3-12 months) should be based on level of concern for malignancy 1

For Masses Suspicious for Malignancy

• Surgery is indicated for masses with features such as:
  • Large size (>4 cm)
  • Heterogeneity
  • Evidence of invasion or necrosis 1
• Open adrenalectomy (rather than laparoscopic) is recommended for masses >5 cm consistent with adrenocortical carcinoma 1

For Hormone-Producing Masses

• All pheochromocytomas must be surgically removed with alpha-blocker therapy for 1-3 weeks prior to surgery 1
• For cortisol-secreting adenomas, surgical resection should be considered, especially in patients with relevant comorbidities 2
• For aldosterone-secreting adenomas, either surgery or medical therapy with mineralocorticoid receptor antagonists is appropriate 1

Special Considerations

For Bilateral Adrenal Incidentalomas

• Each lesion should be separately characterized following the same approach as for unilateral masses 1
• Additional testing should include:
  • Serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1, 3
  • Assessment for adrenal insufficiency in suspected cases of bilateral infiltrative disease, metastases, or hemorrhage 1

For Adrenal Biopsy

• Biopsy has limited clinical value and should not be part of initial workup 1
• Consider biopsy only when:
  • Suspicion of primary adrenal malignancy is remote 1
  • Pathology results would directly influence clinical management (e.g., suspected metastatic disease) 1

Follow-up Recommendations

• For benign-appearing masses that require follow-up, repeat unenhanced CT in 12 months 1
• Annual hormone testing for 4-5 years is recommended to identify new hormone hypersecretion 1
• The risk of missing a malignant lesion justifies the additional radiation of follow-up CT 1

Common Pitfalls to Avoid

• Failing to perform appropriate hormonal evaluation even when imaging suggests benign disease 1
• Using minimally invasive approaches for suspected adrenocortical carcinoma, which can increase recurrence rates and peritoneal spread 1
• Performing unnecessary biopsy of adrenal masses, which has limited value and potential risks 1
• Losing patients to follow-up by not scheduling appropriate monitoring 1