What is the initial lab workup for a patient presenting with an adrenal nodule?

Laboratory Workup for Adrenal Nodules

All patients with adrenal nodules require hormonal screening regardless of size or benign imaging appearance, as approximately 5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment. 1, 2

Universal Screening Tests (Required for All Patients)

Autonomous Cortisol Secretion

• Perform 1 mg overnight dexamethasone suppression test as the preferred screening method for identifying autonomous cortisol secretion (also called mild autonomous cortisol secretion/MACS) 1, 2
• This test is mandatory for all adrenal incidentalomas, even those with unequivocal benign imaging characteristics 1

Pheochromocytoma Screening

• Screen with plasma or 24-hour urinary metanephrines if the nodule displays >10 Hounsfield units (HU) on non-contrast CT OR if the patient has any signs/symptoms of catecholamine excess 1, 2
• Skip pheochromocytoma screening only if the nodule is an unequivocal adrenocortical adenoma confirmed on unenhanced CT (HU <10) AND the patient has no signs or symptoms of adrenergic excess 1
• This distinction is critical because approximately 1/3 of pheochromocytomas can washout in the characteristic range of an adenoma on contrast-enhanced CT, creating a false sense of security 1

Primary Aldosteronism Screening

• Measure aldosterone-to-renin ratio ONLY if the patient has hypertension and/or hypokalemia 1, 2
• This is not a universal screening test—it is conditional based on clinical presentation 1

Conditional Testing

Androgen Excess

• Perform serum androgen testing in cases of suspected adrenocortical carcinoma and/or when clinical signs of virilization are present 1
• This is not part of routine screening but reserved for specific clinical scenarios 1

Critical Pitfalls to Avoid

Never Skip Hormonal Evaluation Based on Imaging Alone

• Even nodules with HU <10 (definitively benign lipid-rich adenomas) require hormonal screening, as imaging cannot predict functional status 1, 2
• Undiagnosed pheochromocytoma can cause life-threatening hypertensive crisis during any surgical procedure, including unrelated surgeries like cataract operations 3

Do Not Perform Routine Adrenal Biopsy

• Adrenal mass biopsy should not be performed routinely for workup of adrenal incidentalomas 1
• Biopsy may only be considered when diagnosis of metastatic disease from extra-adrenal malignancy would change management, and only after pheochromocytoma has been excluded 1
• Biopsy of suspected adrenocortical carcinoma risks tumor seeding along the needle tract 1

Understand Imaging Limitations

• Approximately 1/3 of adrenal adenomas do not washout in the adenoma range on contrast-enhanced CT 1
• Malignant masses can also washout in the adenoma range, potentially causing adrenocortical carcinoma or hypervascular metastases to be mistaken for adenomas 1
• Chemical shift MRI showing heterogeneous signal intensity drop is controversial, as minute amounts of microscopic fat have been identified in pheochromocytoma, adrenocortical carcinoma, and some metastases 1

Special Population Considerations

Patients with History of Extra-Adrenal Malignancy

• The rate of metastatic disease to the adrenal gland is 25-72% depending on primary tumor type 2
• These patients require closer evaluation with lower threshold for biopsy consideration 2

Bilateral Adrenal Nodules

• Up to 15-20% of adrenal nodules are bilateral, representing bilateral adenomas or primary bilateral macronodular adrenal hyperplasia 4
• MACS is seen in 19-44% of patients with adrenal adenomas and is associated with cardiovascular morbidity, poor quality of life, frailty, and increased mortality 4
• Distinguishing unilateral from bilateral MACS may require adrenal vein sampling to guide appropriate therapy 4