What is the management approach for an adrenal nodule?

Management of Adrenal Nodules

All patients with adrenal nodules require comprehensive evaluation including dedicated adrenal imaging (unenhanced CT) and complete hormonal assessment to determine malignancy risk and functional status, with management decisions based on size, imaging characteristics, and hormonal activity. 1, 2

Initial Evaluation

• Unenhanced CT is the first-line imaging modality for all adrenal nodules to determine if the lesion is benign or potentially malignant 1, 2
• Key features to assess on imaging include:
  • Hounsfield units (HU): ≤10 HU suggests benign adenoma 1, 3
  • Size: >4 cm increases risk of malignancy 3, 1
• If initial unenhanced CT is equivocal, proceed to enhanced CT with washout protocol (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

Hormonal Evaluation

• All patients with adrenal nodules require complete hormonal assessment regardless of symptoms 2, 1
• Initial hormonal testing should include:
  • 1 mg overnight dexamethasone suppression test (cutoff value of serum cortisol ≤50 nmol/L or ≤1.8 µg/dL) 2, 4
  • Plasma-free and/or urinary fractionated metanephrines to rule out pheochromocytoma 1, 5
  • Aldosterone-to-renin ratio if hypertension or hypokalemia is present 1
  • For suspected adrenocortical carcinoma, include levels of sex hormones and steroid precursors 1

Management Algorithm Based on Imaging and Functional Status

Benign-Appearing, Non-Functioning Adrenal Masses

• For masses <4 cm with ≤10 HU, no further follow-up imaging or functional testing is required 1, 6
• For masses ≥4 cm that appear radiologically benign (<10 HU), repeat imaging in 6-12 months 1, 3

Indeterminate or Potentially Malignant Masses

• For indeterminate non-functioning lesions, management options include:
  • Repeat imaging in 3-12 months 1, 3
  • Surgical resection if concerning features present 3, 1
• Multidisciplinary team discussion is recommended for indeterminate imaging 3, 2
• Surgery is indicated for:
  • Masses >4 cm with suspicious features 1, 3
  • Any nodule with significant growth (>5 mm/year) 1, 2
  • Hormone-secreting nodules 2, 1
  • Imaging features concerning for malignancy (heterogeneity, invasion, necrosis) 1

Functioning Adrenal Masses

• For aldosterone-secreting adenomas:
  • Confirm diagnosis with saline challenge 3
  • Consider bilateral adrenal vein sampling to lateralize production 3
  • Laparoscopic adrenalectomy is recommended 3
  • When surgery is not possible, treat with mineralocorticoid receptor antagonist 3
• For patients with mild autonomous cortisol secretion (MACS):
  • Screen for cortisol-related comorbidities (hypertension, type 2 diabetes) 4
  • Consider surgical treatment in patients with relevant comorbidities 4

Follow-up Recommendations

• For benign-appearing masses that require follow-up, repeat unenhanced CT in 12 months 1, 3
• Follow-up protocols vary among guidelines:
  • European Society of Endocrinology (ESE) and American College of Radiology (ACR): no follow-up imaging for benign-appearing masses 3, 6
  • American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons (AACE/AAES): reimaging in 3-6 months, then annually for 1-2 years if stable 3
  • Canadian Urological Association (CUA): reimaging at 12 months, then annual clinical follow-up for 4 years 3
• Hormonal follow-up recommendations also vary:
  • ESE: no additional hormonal testing if initial values were normal 3
  • AACE/AAES: annual hormonal panel for 5 years 3
  • CUA: annual testing for 4 years 3
  • Korean Endocrine Society (KES): annual testing for 4-5 years if tumor is >3 cm 3

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 1
• Performing unnecessary biopsy of adrenal masses 1, 7
• Losing patients to follow-up by not scheduling appropriate monitoring 1
• Assuming all bilateral adrenal nodules represent metastatic disease 6

Special Considerations

• For bilateral adrenal incidentalomas, each lesion should be separately characterized 1, 6
• Consider measuring serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia in bilateral cases 1, 6
• Adrenal biopsy has limited clinical value and should not be part of initial workup 1, 7