What is the management approach for an adrenal nodule?

Management of Adrenal Nodules

All adrenal nodules require both complete hormonal evaluation and unenhanced CT imaging for initial characterization, with subsequent management determined by size, imaging characteristics (Hounsfield units), and functional status. 1, 2

Initial Imaging Evaluation

Unenhanced CT is the mandatory first-line imaging modality for all adrenal nodules. 1 The critical measurement is Hounsfield units (HU):

• ≤10 HU indicates a benign adenoma regardless of size 1, 3
• Lesions <-10 HU represent lipid-rich adenomas with even higher confidence of benignity 4
• HU >10 requires further characterization with enhanced CT washout protocol (60% absolute/40% relative washout suggests benign pathology) 1
• Homogeneous lesions ≤10 HU require no additional imaging independent of size 3

MRI with chemical shift imaging is reserved for high-risk populations including pregnant women and patients <40 years old. 1

Mandatory Hormonal Evaluation

Every patient with an adrenal nodule requires complete hormonal assessment regardless of symptoms or imaging appearance, as approximately 5% of radiologically benign-appearing lesions harbor subclinical hormone production. 2, 5

Required initial testing includes:

• 1 mg overnight dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 µg/dL is normal) 1, 3
• Plasma-free and/or urinary fractionated metanephrines to exclude pheochromocytoma 1, 5
• Aldosterone-to-renin ratio if hypertension or hypokalemia present 1
• Sex hormones and steroid precursors if adrenocortical carcinoma suspected 1

Management Algorithm Based on Size and Imaging

Benign-Appearing Lesions (≤10 HU)

For masses <4 cm with ≤10 HU and normal hormonal evaluation, no further follow-up imaging or functional testing is required. 1, 2 This applies to both unilateral and bilateral nodules. 4

For masses ≥4 cm with ≤10 HU (radiologically benign), repeat imaging at 6-12 months is recommended due to higher malignancy risk associated with larger size, even when imaging suggests benignity. 1, 2 Most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis. 2

Indeterminate or Suspicious Lesions

Lesions >4 cm that are inhomogeneous or have HU >20 require multidisciplinary team discussion, with surgery being the usual management choice due to sufficiently high malignancy risk. 1, 3

Surgery is indicated for:

• Masses >4 cm with suspicious radiological features 1
• Any hormone-secreting nodule 1
• Growth >5 mm/year on follow-up imaging 1, 2

Follow-up Protocols for Non-Operated Lesions

There is divergence among major guidelines regarding follow-up:

• European Society of Endocrinology and American College of Radiology recommend no follow-up imaging for benign-appearing masses <4 cm with ≤10 HU 1
• American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons recommend reimaging at 3-6 months, then annually for 1-2 years if stable 1
• Canadian Urological Association recommends reimaging at 12 months, then annual clinical follow-up for 4 years 1

Growth rate thresholds for decision-making:

• <3 mm/year: no further imaging or functional testing required 2
• >5 mm/year: consider adrenalectomy after repeating functional workup 2

Hormonal Follow-up Controversy

• American Urological Association (2023) does not recommend repeat hormonal testing if initial workup was normal 2
• American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons recommend annual hormonal panel for 5 years 2

Given the low but real risk of developing hormonal hypersecretion over time, consider annual hormonal screening for at least 2-3 years in patients with lesions ≥4 cm or those with comorbidities potentially attributable to cortisol excess. 2, 3

Special Populations and Considerations

Bilateral adrenal nodules: Each lesion requires separate characterization using the same principles. 1, 4 Measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 1

Patients with extra-adrenal malignancy: Require closer evaluation even for smaller lesions, as metastatic risk ranges from 25-72% depending on primary tumor. 2 However, bilateral adenomas are common in older patients and should not be automatically assumed to represent metastatic disease. 4

Young adults, children, and pregnant patients: Require expedited evaluation as adrenal lesions are more likely malignant in these populations. 2

Critical Pitfalls to Avoid

Never perform routine adrenal mass biopsy for workup of adrenal incidentalomas - it is rarely indicated and carries risks including potential tumor seeding. 2 Biopsy should only be considered after pheochromocytoma has been biochemically excluded and in select cases where metastatic disease is suspected. 2

Do not skip initial hormonal evaluation even for radiologically benign-appearing lesions, as functional status cannot be reliably determined by imaging alone. 2, 5

Do not confuse management of lipid-rich adenomas (HU <10) with indeterminate masses (HU >10), which require more extensive follow-up and often surgical intervention. 4