What are the recommended referrals, diagnostic testing, and imaging for an enlarging adrenal nodule?

Management of an Enlarging Adrenal Nodule: Diagnostic Testing and Referrals

For an enlarging adrenal nodule, immediate referral to a multidisciplinary team including endocrinologists, surgeons, and radiologists is essential, followed by comprehensive hormonal evaluation and adrenal protocol imaging to determine malignancy risk and functional status. 1

Initial Imaging Evaluation

• Non-contrast CT is the first-line imaging modality for all adrenal nodules to determine if the lesion is benign or potentially malignant 1
• Key features to assess on non-contrast CT:
  • Hounsfield units (HU) measurement (<10 HU suggests benign adenoma) 1, 2
  • Size (>4 cm increases risk of malignancy) 1
  • Homogeneity and margin characteristics 3
• For indeterminate lesions on non-contrast CT, second-line imaging should include either:
  • CT with contrast washout protocol (>50% washout suggests benign adenoma) 1, 2
  • Chemical-shift MRI to detect microscopic fat 2, 4

Comprehensive Hormonal Evaluation

All patients with enlarging adrenal nodules require complete hormonal assessment regardless of symptoms 5:

1. Cortisol secretion assessment:

   • 1 mg overnight dexamethasone suppression test (preferred screening test) 1, 5
   • Plasma ACTH levels 5

2. Catecholamine excess screening:

   • Plasma or 24-hour urinary metanephrines for all patients with adrenal masses >10 HU or with symptoms of catecholamine excess 1, 5
   • Critical to perform before any invasive procedures including biopsy 5

3. Aldosterone secretion assessment:

   • Aldosterone-to-renin ratio for patients with hypertension and/or hypokalemia 1, 5
   • Consider confirmatory testing with saline challenge if initial results are abnormal 1

4. Androgen excess testing:

   • Serum DHEA-S, androstenedione, and 17-beta-estradiol in cases of suspected adrenocortical carcinoma or clinical signs of virilization 1, 5

Growth Rate Assessment and Management

• An adrenal nodule growth rate >3 mm/year is highly suspicious for malignancy (100% sensitivity and specificity) 6
• Benign adenomas may grow at rates up to 2.8 mm/year, but malignant nodules typically grow at rates >5 mm/year 6
• Management algorithm based on growth rate:
  • Growth <3 mm/year: Likely benign, continue observation 6
  • Growth >3 mm/year: High suspicion for malignancy, surgical evaluation recommended 6

Referrals

• Endocrinology: Required for all patients with enlarging adrenal nodules or evidence of hormone hypersecretion 1, 5
• Surgical consultation: Indicated for:
  • Nodules >4 cm in diameter 1, 7
  • Any nodule with significant growth (>3 mm/year) 6
  • Hormone-secreting nodules 1
  • Imaging features concerning for malignancy 1
• Multidisciplinary tumor board: Recommended for indeterminate lesions or suspected adrenocortical carcinoma 1

Follow-up Recommendations

• For non-functioning nodules <4 cm with benign imaging features:

  • Repeat imaging in 6-12 months to assess stability 1
  • If stable, no further imaging follow-up is required according to some guidelines (ESE, ACR) 1
  • Other guidelines (AACE/AAES, CUA) recommend annual imaging for 1-2 years 1

• For indeterminate nodules:

  • Repeat imaging in 3-6 months 1
  • If significant growth is observed, surgical evaluation is recommended 1

Important Caveats

• Adrenal biopsy should not be performed routinely and is contraindicated before excluding pheochromocytoma 1, 8
• Radiological appearance cannot reliably predict hormone secretion status; comprehensive hormonal evaluation is essential regardless of imaging features 5
• Even subtle hormone production can impact surgical management and perioperative care 5
• Growth rate is a critical factor in determining malignancy risk and should be carefully monitored 6