What is the recommended follow-up protocol for an adrenal incidentaloma?

Follow-up Protocol for Adrenal Incidentalomas

The follow-up strategy for adrenal incidentalomas is determined by size, imaging characteristics, and functional status, with most benign non-functional adenomas <4 cm requiring no further imaging or hormonal testing after initial workup. 1

Lesions Requiring No Further Follow-up

Patients with benign non-functional adenomas <4 cm, myelolipomas, and other small masses containing macroscopic fat do not require any additional follow-up imaging or functional testing after initial characterization. 1

This applies specifically to lesions that meet ALL of the following criteria:

• Homogeneous appearance with <10 HU on non-contrast CT 1
• No hormonal hypersecretion on initial screening 1
• Size <4 cm 1

Size-Based Follow-up Algorithm

Lesions ≥4 cm (Radiologically Benign)

• Repeat imaging at 6-12 months even if the lesion appears benign on initial CT 1
• This recommendation exists because most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis 1

Indeterminate Lesions (Any Size)

• Repeat imaging in 3-6 months OR consider surgical resection based on shared decision-making 1
• Multidisciplinary review by endocrinologists, surgeons, and radiologists should occur when imaging is not consistent with a benign lesion 1

Growth Rate Thresholds

Growth rate determines whether continued surveillance or intervention is needed: 1

• <3 mm/year: No further imaging or functional testing required 1
• >5 mm/year: Adrenalectomy should be considered after repeating functional workup 1
• 3-5 mm/year: Continue surveillance with clinical judgment

Hormonal Follow-up

For Initially Non-functional Lesions

There is significant variation in guideline recommendations for hormonal follow-up:

• CUA/AUA guidelines (2023): No specific recommendation for repeat hormonal testing if initial workup was normal 1
• AACE/AAES guidelines: Annual hormonal panel for 5 years 1
• KES guidelines: Annual testing for 4-5 years if tumor >3 cm 1

Given the conflicting evidence and the 17% cumulative risk of developing endocrine abnormalities at 1 year and 47% at 5 years 2, a pragmatic approach is annual hormonal screening (1 mg dexamethasone suppression test) for lesions ≥3 cm for at least 2 years, as the risk is highest during this period. 2

For Mild Autonomous Cortisol Secretion (MACS)

• Annual clinical screening for new or worsening metabolic comorbidities (hypertension, diabetes, osteoporosis) in patients not managed surgically 1
• The 1 mg dexamethasone suppression test is the preferred screening test, with cortisol >50 nmol/L (>1.8 μg/dL) indicating possible autonomous secretion 1, 3

Special Populations

Patients with History of Extra-adrenal Malignancy

• Closer evaluation required even for smaller lesions, as metastatic risk ranges from 25-72% depending on primary tumor 4
• The standard size thresholds do not apply in this population 5

Young Adults, Children, and Pregnant Patients

• Expedited evaluation as adrenal lesions are more likely malignant in these populations 1
• Consider low-dose CT or chemical shift MRI to minimize radiation exposure 1

Bilateral Adrenal Incidentalomas

• Each lesion should be characterized separately using the same criteria as unilateral lesions 1
• Additional testing: measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1
• Assess for adrenal insufficiency in suspected bilateral infiltrative disease, metastases, or hemorrhage 1

Critical Pitfalls to Avoid

Do not perform routine adrenal mass biopsy for workup of adrenal incidentalomas, as this is rarely indicated and carries risks including potential tumor seeding 1

Do not skip initial hormonal evaluation even for radiologically benign-appearing lesions, as approximately 5% harbor subclinical hormone production requiring treatment 5

Be aware of washout CT limitations: approximately one-third of pheochromocytomas may washout in the characteristic range of an adenoma, and one-third of adenomas do not washout in the adenoma range 1

Do not continue indefinite imaging for stable lesions <4 cm with benign characteristics, as this leads to unnecessary radiation exposure, patient anxiety, and healthcare costs 6