What is the appropriate workup for incidental small bilateral adrenal nodules?

Workup for Incidental Small Bilateral Adrenal Nodules

For small bilateral adrenal nodules, each lesion must be separately characterized with both imaging and hormonal evaluation, regardless of size or bilateral presentation. 1

Initial Imaging Characterization

Obtain unenhanced CT as the first-line imaging modality to determine Hounsfield units (HU) for each nodule. 2

• Nodules with ≤10 HU are benign adenomas and require no further imaging follow-up if <4 cm 1, 2, 3
• Nodules with HU <-10 represent lipid-rich adenomas with even higher confidence of benignity 3
• If HU >10, proceed to enhanced CT with washout protocol (absolute washout ≥60% or relative washout ≥40% suggests benign pathology) 2
• Chemical shift MRI is an alternative second-line test, particularly for younger patients (<40 years), pregnant women, or when radiation exposure is a concern 1, 2

A critical pitfall: Recent evidence shows that washout CT has limited utility in true incidentalomas without known malignancy, with malignancy prevalence of only 0.3% in nodules <4 cm regardless of washout values. 4 However, guidelines still recommend this approach for indeterminate lesions. 2

Mandatory Hormonal Evaluation

All patients with bilateral adrenal incidentalomas require complete hormonal assessment regardless of imaging appearance or symptoms. 2, 5

Required Tests:

• 1 mg overnight dexamethasone suppression test (cutoff: serum cortisol ≤50 nmol/L or ≤1.8 µg/dL indicates normal suppression) 2, 5, 6
• Plasma-free and/or urinary fractionated metanephrines to exclude pheochromocytoma 2
• Aldosterone-to-renin ratio if hypertension or hypokalemia is present 2
• Serum 17-hydroxyprogesterone specifically for bilateral cases to exclude congenital adrenal hyperplasia 1, 2

Critical consideration: Approximately 5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment, making hormonal evaluation non-negotiable. 7

Special Considerations for Bilateral Presentation

Assess for adrenal insufficiency in suspected cases of bilateral infiltrative disease, metastases, or hemorrhage. 1 While extremely unlikely with lipid-rich adenomas (HU <-10), this becomes relevant if imaging characteristics are atypical. 3

Do not assume bilateral nodules represent metastatic disease—bilateral adenomas are common, especially in older patients. 3

Management Algorithm Based on Size and Imaging

For nodules <4 cm with HU ≤10:

• No further imaging follow-up or functional testing required (strong recommendation, moderate quality evidence) 1, 2, 7
• This applies to each nodule independently in bilateral cases 1

For nodules ≥4 cm even if radiologically benign (HU <10):

• Repeat imaging in 6-12 months due to slightly higher malignancy risk with larger size 1, 2
• Most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis 1, 7

For indeterminate nodules (HU >10 without definitive benign features):

• Shared decision-making between patient and clinician regarding repeat imaging in 3-6 months versus surgical resection 1
• Multidisciplinary team discussion is recommended 2

Follow-up Recommendations for Non-Operated Nodules

If follow-up imaging is performed:

• Growth <3 mm/year requires no further imaging or functional testing 1, 2
• Growth >5 mm/year warrants consideration for adrenalectomy after repeating functional workup 1, 2, 7

Guideline discrepancy exists: The European Society of Endocrinology and American College of Radiology recommend no follow-up imaging for benign-appearing masses, while AACE/AAES recommend reimaging in 3-6 months then annually for 1-2 years, and CUA recommends reimaging at 12 months then annual clinical follow-up for 4 years. 2 Given the strong evidence that nodules <4 cm with HU ≤10 have extremely low malignancy risk (0.3%), no follow-up imaging is the most appropriate approach. 4

Age-Specific Considerations

Young adults, children, and pregnant patients require expedited evaluation as adrenal lesions are more likely malignant in these populations. 1 Consider low-dose CT or chemical shift MRI for radiation safety. 1, 2

Common Pitfalls to Avoid

• Never skip initial hormonal evaluation even for radiologically benign bilateral lesions—subclinical hormone excess occurs in 5% of incidentalomas 7
• Do not routinely perform adrenal biopsy—reserve only for cases where noninvasive techniques are equivocal with high suspicion for metastatic disease 1, 7
• Do not confuse management of lipid-rich adenomas (HU <10) with indeterminate masses (HU >10), which require more extensive follow-up 3