What is the appropriate management for an adult over 50 years old with an adrenal incidentaloma and no significant past medical history?

Management of Adrenal Incidentaloma in Adults Over 50

All adults over 50 with an adrenal incidentaloma require both comprehensive hormonal screening and radiological characterization, regardless of symptoms, with management determined by imaging features, size, and functional status. 1

Initial Radiological Assessment

Obtain non-contrast CT as the mandatory first-line imaging study to characterize the mass and assess malignancy risk. 1

Key imaging features to evaluate:

• Hounsfield Units (HU) ≤10 on unenhanced CT: These homogeneous, well-circumscribed lesions are definitively benign adenomas regardless of size and require no further imaging workup. 1, 2
• HU 10-20: Low risk (0.5%) for adrenocortical carcinoma. 1
• HU >20: Higher risk (6.3%) for malignancy, requiring further evaluation. 1
• Masses containing macroscopic fat (myelolipomas): Benign, no further workup needed. 3, 2

If initial non-contrast CT is indeterminate (HU >10), proceed to second-line imaging with either contrast-enhanced CT with washout protocol or chemical-shift MRI. 1

Mandatory Hormonal Evaluation

Every patient requires complete hormonal screening regardless of symptoms or benign-appearing imaging. 1, 2

Required hormonal tests:

• 1 mg overnight dexamethasone suppression test: Screen all patients for autonomous cortisol secretion (cortisol >50 nmol/L or >1.8 µg/dL indicates autonomous secretion). 1, 4
• Plasma free metanephrines or 24-hour urinary fractionated metanephrines: Screen for pheochromocytoma in all patients with HU >10 or any signs/symptoms of catecholamine excess. 1, 2
  • Critical exception: Skip pheochromocytoma screening only if HU <10 on unenhanced CT AND no adrenergic symptoms. 1
• Aldosterone-to-renin ratio: Screen only if hypertension and/or hypokalemia present. 1, 3
• Sex hormones and steroid precursors: Only if suspected adrenocortical carcinoma or virilization signs present. 1

Management Algorithm Based on Size, Imaging, and Function

Immediate surgical referral indicated for:

• Any hormonally active tumor (overt Cushing's syndrome, pheochromocytoma, aldosterone-producing adenoma). 1, 2
• Masses >4 cm with suspicious imaging features (HU >20, inhomogeneous, irregular borders). 1, 4
• Any mass growing >5 mm/year on surveillance imaging. 5, 2

Conservative management with surveillance:

• Masses <4 cm with HU ≤10: No further imaging or functional testing required. 5, 3
• Masses <4 cm with HU 10-20 and benign appearance: Follow-up imaging at 12 months, then discontinue if stable. 3, 2

Special consideration for mild autonomous cortisol secretion (MACS):

• Patients with post-dexamethasone cortisol >50 nmol/L (>1.8 µg/dL) without overt Cushing's syndrome have increased morbidity and mortality risk. 4
• Screen aggressively for and treat cortisol-related comorbidities (hypertension, type 2 diabetes, osteoporosis, obesity). 2, 4
• Consider adrenalectomy in younger patients with MACS and progressive metabolic comorbidities attributable to cortisol excess after shared decision-making. 1, 4

Follow-Up Protocol for Non-Surgical Cases

For masses requiring surveillance:

• Repeat unenhanced CT at 12 months. 3, 2
• Discontinue imaging if no growth after 1-2 years of stability. 2
• Annual hormonal screening for 4-5 years for masses >3 cm due to risk of developing new hormone secretion. 2

For masses <4 cm with HU ≤10 or myelolipomas: No follow-up imaging or hormonal testing required. 5, 3

Critical Pitfalls to Avoid

• Never perform adrenal biopsy routinely. Biopsy is only considered when metastatic disease from extra-adrenal malignancy would directly change management, and only after pheochromocytoma is definitively excluded (failure to exclude pheochromocytoma before biopsy can be fatal). 1, 2
• Do not skip pheochromocytoma screening in appropriate patients. Missing this diagnosis before surgery or biopsy carries significant mortality risk. 2
• Avoid unnecessary repeated imaging for small masses with benign characteristics (HU ≤10), as this increases radiation exposure, patient anxiety, and healthcare costs without clinical benefit. 5
• Maintain low threshold for multidisciplinary review (endocrinology, surgery, radiology) when imaging is indeterminate, hormone hypersecretion is present, significant growth occurs, or surgery is considered. 1, 2

Special Populations

For patients with known extra-adrenal malignancy: Adrenal masses are more likely malignant, and even smaller lesions warrant aggressive evaluation with non-contrast CT, chemical-shift MRI, or FDG-PET if non-invasive imaging is equivocal. 1

For bilateral adrenal incidentalomas: Each lesion must be characterized separately using the same protocol as unilateral masses, and consider measuring 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 3, 2