What is the appropriate diagnostic and treatment approach for a patient with an adrenal mass?

Diagnostic and Treatment Approach for Adrenal Mass

Initial Mandatory Evaluation

All patients with an adrenal mass ≥1 cm must undergo comprehensive hormonal screening and imaging characterization, regardless of appearance or symptoms, to prevent life-threatening complications and guide appropriate management. 1

Hormonal Screening (Required for ALL Patients)

Every patient requires a 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion, administered at 11 PM with serum cortisol measured at 8 AM the next morning. 2, 3, 4 This is non-negotiable even for small, benign-appearing masses, as autonomous cortisol secretion occurs in 5.3% of incidentalomas. 4

Interpretation of dexamethasone suppression test: 2, 4

• ≤50 nmol/L (1.8 μg/dL): Excludes autonomous cortisol secretion
• 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion

• 138 nmol/L (>5.0 μg/dL): Confirms autonomous cortisol secretion

Conditional hormonal testing based on specific features:

• Pheochromocytoma screening (plasma free metanephrines or 24-hour urinary fractionated metanephrines): Required if mass ≥10 Hounsfield Units (HU) on non-contrast CT OR any symptoms of catecholamine excess (hypertension, headaches, palpitations, sweating). 1, 2, 3 This must be excluded before any biopsy to prevent hypertensive crisis. 1

• Primary aldosteronism screening (aldosterone-to-renin ratio): Required if patient has hypertension and/or hypokalemia, with ratio >20 ng/dL per ng/mL/hr indicating hyperaldosteronism. 2, 3, 4

• Androgen testing (DHEAS, testosterone): Only if virilization, feminization, or suspected adrenocortical carcinoma. 1, 2

Imaging Protocol

First-line: Non-contrast CT of abdomen and pelvis to characterize the mass. 1, 4

Benign features (no further imaging needed): 1

• Homogeneous mass <10 HU on non-contrast CT (lipid-rich adenoma)
• Myelolipomas or masses with macroscopic fat
• Simple cysts

For indeterminate masses (>10 HU on non-contrast CT): Proceed with second-line imaging using either washout CT or chemical shift MRI. 1

Critical caveat: Approximately one-third of pheochromocytomas may washout in the adenoma range, and one-third of adenomas do not washout appropriately. 1 Malignant masses can also demonstrate washout patterns mimicking adenomas. 1

For suspected malignancy: Cross-sectional imaging of chest, abdomen, and pelvis is mandatory to assess for metastases, local invasion, or vena cava extension. 1

Treatment Algorithm

Surgical Indications (Adrenalectomy Required)

Functional tumors requiring surgery: 1

• Clinically apparent Cushing's syndrome (unilateral cortisol-secreting adenoma)
• Aldosterone-secreting adenomas
• Pheochromocytomas
• Use minimally invasive surgery when feasible for these lesions

Size and imaging-based indications: 1

• Masses >4 cm with suspicious features (inhomogeneous, irregular margins, >20 HU)
• Growth >5 mm/year on surveillance (repeat functional workup first)
• Suspected adrenocortical carcinoma

Surgical approach for adrenocortical carcinoma: 1

• Minimally invasive adrenalectomy acceptable if tumor can be resected without capsule rupture
• Open adrenalectomy for larger tumors, locally advanced disease, lymph node metastases, or tumor thrombus

Conservative Management with Surveillance

No further follow-up required for: 1

• Benign non-functional adenomas <4 cm with <10 HU
• Myelolipomas
• Small masses with macroscopic fat

Surveillance protocol for non-functional lesions ≥4 cm but radiologically benign (<10 HU): 1

• Repeat imaging at 6-12 months
• If growth <3 mm/year: No further imaging or functional testing needed
• If growth 3-5 mm/year: Continue surveillance
• If growth >5 mm/year: Repeat functional workup and consider adrenalectomy

For indeterminate non-functional masses: Shared decision-making between repeat imaging in 3-6 months versus surgical resection. 1

Special consideration for mild autonomous cortisol secretion: Younger patients with progressive metabolic comorbidities attributable to cortisol excess can be considered for adrenalectomy after shared decision-making; otherwise, annual clinical screening for new or worsening comorbidities. 1

Critical Pitfalls to Avoid

Never perform adrenal biopsy routinely. 1, 4 Biopsy is only considered when diagnosing metastatic disease from extra-adrenal malignancy would change management, and only after pheochromocytoma has been definitively excluded. 1 Biopsy of suspected adrenocortical carcinoma risks tumor seeding. 1

Do not skip dexamethasone suppression testing even in small, benign-appearing masses. 4

In patients with known extra-adrenal malignancy: Nearly 50% of adrenal masses in this population are independent primary adrenal tumors (not metastases), including functional neoplasms requiring different management. 5 Standard hormonal evaluation is mandatory. 5

For bilateral adrenal masses: Each lesion requires separate characterization, and measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 2