What is the recommended approach for investigating an enlarging adrenal nodule?

Investigation of an Enlarging Adrenal Nodule

Adrenalectomy should be considered for any adrenal nodule growing >5 mm/year after repeating functional work-up, as this growth rate indicates potential malignancy regardless of initial imaging characteristics. 1

Initial Assessment of Growth Rate

The growth rate is the critical determinant for management:

• Growth >5 mm/year: Proceed directly to surgical evaluation after repeating hormonal work-up 1
• Growth 3-5 mm/year: Continue surveillance with repeat imaging in 6-12 months 1, 2
• Growth <3 mm/year: No further imaging or functional testing required 1

Mandatory Functional Re-evaluation

Before any surgical decision for an enlarging nodule, repeat the complete hormonal work-up: 1

• 1 mg dexamethasone suppression test for autonomous cortisol secretion (all patients) 1
• Aldosterone-to-renin ratio if hypertension or hypokalemia present 1
• Plasma or 24-hour urinary metanephrines if nodule >10 HU on non-contrast CT or any signs of catecholamine excess 1
• Serum androgen testing if virilization signs present 1

Repeat Imaging Characterization

For an enlarging nodule, obtain updated imaging to reassess malignancy risk: 1, 3

• Non-contrast CT: Measure current Hounsfield units (HU <10 suggests benign, but growth overrides this) 1, 3
• If indeterminate (>10 HU): Perform washout CT or chemical shift MRI 1, 3

Critical Imaging Pitfalls

• Approximately 1/3 of pheochromocytomas can washout like adenomas on CT 1, 3
• Approximately 1/3 of adenomas do not washout in the typical adenoma range 1, 3
• Malignant masses (including adrenocortical carcinoma) can occasionally demonstrate adenoma-like washout patterns 1, 3

Multidisciplinary Review

Obtain multidisciplinary review by endocrinologists, surgeons, and radiologists when: 1

• Tumor has grown significantly during follow-up (especially >5 mm/year)
• Imaging is not consistent with a benign lesion
• Evidence of hormone hypersecretion develops
• Adrenal surgery is being considered

Surgical Approach Based on Suspicion

If Suspected Adrenocortical Carcinoma:

• Minimally-invasive adrenalectomy can be offered if the tumor can be safely resected without rupturing the capsule 1
• Open adrenalectomy should be considered for larger tumors or those with locally advanced features, lymph node metastases, or tumor thrombus 1

If Functional Tumor Identified:

• Unilateral adrenalectomy (minimally-invasive when feasible) for cortisol-secreting masses with Cushing's syndrome, aldosterone-secreting masses, or pheochromocytomas 1

Role of Biopsy

Adrenal mass biopsy should NOT be performed routinely for enlarging nodules: 1, 3

• Only consider if diagnosis of metastatic disease from extra-adrenal malignancy would change management 1, 3
• Never biopsy suspected adrenocortical carcinoma due to risk of tumor seeding 1
• Must exclude pheochromocytoma biochemically before any biopsy attempt 1, 3

Special Considerations for Size

• Nodules ≥4 cm: Even if radiologically benign (<10 HU), growth >5 mm/year warrants surgery due to higher baseline malignancy risk 1, 2
• **Nodules <4 cm**: Growth rate is the primary determinant, but size >6 cm historically indicates high malignancy risk 4

Common Pitfalls to Avoid

• Do not rely solely on initial benign imaging characteristics (HU <10) if the nodule is enlarging significantly 1, 3
• Do not delay surgical evaluation for nodules growing >5 mm/year while waiting for additional imaging 1
• Do not assume bilateral nodules represent metastatic disease; bilateral adenomas are common, but each nodule requires separate characterization 1, 5
• Do not proceed with surgery without first excluding pheochromocytoma biochemically to avoid intraoperative hypertensive crisis 1