What is the recommended workup for a 3 cm left adrenal nodule with characteristics suggestive of an adenoma on imaging?

Management of a 3 cm Left Adrenal Nodule with Signal Loss on Out-of-Phase Images

For a 3 cm left adrenal nodule demonstrating diffuse intralesional hypointense signal on out-of-phase images relative to in-phase images, biochemical evaluation for hormone excess is recommended, with no further imaging follow-up needed as this represents a benign adenoma. 1

Radiological Interpretation

The imaging findings described in the question are classic for an adrenal adenoma:

• Signal loss on out-of-phase images compared to in-phase images on MRI is diagnostic of intracellular lipid content
• This chemical-shift MRI finding is highly specific for benign adrenal adenomas 2, 1
• The 3 cm size places this nodule in a relatively low-risk category for malignancy 2

Recommended Workup Algorithm

1. Hormonal Evaluation (Required for ALL adrenal nodules)

Even though the imaging characteristics strongly suggest a benign adenoma, all adrenal nodules require hormonal evaluation to rule out subclinical hormone excess 1:

• Cortisol secretion: 1 mg overnight dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 μg/dL indicates normal suppression) 1, 3
• Catecholamine excess: Plasma or 24-hour urinary metanephrines to exclude pheochromocytoma 1
• Aldosterone production: Aldosterone-to-renin ratio if hypertension is present 1

2. Imaging Follow-up

• No additional imaging is required for this nodule as:
  • The size is less than 4 cm
  • The chemical-shift MRI findings are diagnostic of a lipid-rich adenoma 2, 1
  • The ACR Appropriateness Criteria states that small (<3 cm) incidentally discovered adrenal masses with benign imaging characteristics do not justify extensive and costly workup 2

3. Management Based on Hormonal Evaluation Results

• If non-functioning: No further follow-up needed 2, 1
• If hormone-producing:
  • Cortisol excess: Consider adrenalectomy (laparoscopic when feasible) with postoperative corticosteroid supplementation 2
  • Aldosterone excess: Adrenalectomy (laparoscopic preferred) for unilateral aldosterone production 2
  • Catecholamine excess: Surgical resection after appropriate alpha-blockade 1

Important Considerations

• Size threshold: While this 3 cm nodule falls at the borderline of size criteria, the definitive chemical-shift MRI findings of lipid content strongly support benign etiology 2, 1
• Subclinical function: Studies have shown that 5-23% of incidentally discovered adrenal masses may have subclinical hormone production despite being asymptomatic 2
• Malignancy risk: The risk of malignancy for adrenal nodules <4 cm with benign imaging characteristics (like lipid-rich adenomas) is extremely low (approximately 0%) 1

Common Pitfalls to Avoid

• Unnecessary follow-up imaging for lipid-rich adenomas <4 cm with benign characteristics wastes resources and causes patient anxiety 1
• Failure to perform hormonal evaluation even for small adenomas can lead to missed diagnosis of subclinical hormone excess 1
• Performing adrenal biopsy is rarely indicated for adrenal masses with characteristic imaging features of adenoma and should be avoided 1, 4
• Overlooking the possibility of mild autonomous cortisol secretion (MACS), which can contribute to metabolic complications even without overt Cushing's syndrome 3

This nodule demonstrates classic imaging features of a benign adrenal adenoma, and with appropriate hormonal evaluation, no further imaging follow-up is needed unless hormonal abnormalities are detected.