What is the recommended follow-up schedule for a small adrenal nodule likely representing an adenoma?

Follow-Up Schedule for Small Adrenal Adenomas

Patients with small (<4 cm) benign non-functional adenomas confirmed on imaging (≤10 HU on non-contrast CT) do not require any follow-up imaging or repeat functional testing after initial characterization. 1, 2, 3

Initial Requirements Before Discontinuing Follow-Up

Before concluding no follow-up is needed, the nodule must meet ALL of the following criteria:

• Size <4 cm on initial imaging 1, 2
• Homogeneous appearance with ≤10 HU on non-contrast CT, confirming lipid-rich adenoma 1, 2
• No hormonal hypersecretion on initial screening (1 mg dexamethasone suppression test, plasma/urinary metanephrines, and aldosterone-to-renin ratio if hypertensive) 1, 2

Size-Based Follow-Up Algorithm

For Nodules <4 cm with Benign Features

• No further imaging or functional testing required after initial complete evaluation 1, 2, 3
• This strong recommendation is based on the extremely low risk of malignancy in this population, with no cases of adrenocortical carcinoma developing in 392 patients followed for mean 6.7 years 4

For Nodules ≥4 cm (Even if Radiologically Benign)

• Repeat imaging at 6-12 months is mandatory 1, 2, 3
• Most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis, justifying closer surveillance 2, 3
• If stable at 6-12 months with growth <3 mm/year, no further imaging needed 1, 2

Growth Rate Thresholds on Follow-Up Imaging (If Performed)

• <3 mm/year growth: No further imaging or functional testing required 1, 2, 3
• >5 mm/year growth: Adrenalectomy should be considered after repeating complete functional workup 1, 2, 3

Discrepancy in Repeat Hormonal Testing

There is notable divergence among guidelines regarding repeat hormonal screening:

• American Urological Association (2023): No repeat hormonal testing if initial workup normal 2
• American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons: Annual hormonal panel for 5 years 1, 2

The most recent high-quality guideline (AUA 2023) does not recommend repeat hormonal testing for radiologically benign, non-functional adenomas <4 cm, which aligns with the low risk of developing clinically significant hormone excess in this population 1, 2.

Critical Exceptions Requiring Different Management

History of Extra-Adrenal Malignancy

• The <4 cm threshold does NOT apply 2, 3
• Metastatic risk ranges from 25-72% depending on primary tumor 2, 3
• Requires closer evaluation regardless of benign imaging features 2, 3

Young Adults, Children, and Pregnant Patients

• Require expedited evaluation as adrenal lesions are more likely malignant in these populations 2, 3
• Standard observation protocols do not apply 2, 3

Common Pitfalls to Avoid

• Skipping initial hormonal evaluation: Approximately 5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment 2, 3
• Performing routine adrenal biopsy: Rarely indicated and carries risks including potential tumor seeding 1, 2, 3
• Following older guidelines recommending 3-6 month initial imaging: The 2023 AUA guideline clarifies that benign-appearing adenomas <4 cm require no follow-up imaging at all 1, 2
• Assuming all guidelines agree on repeat hormonal testing: The most recent AUA guideline (2023) does not recommend this, while older AACE/AAES guidelines do 1, 2