All adrenal abnormalities should be evaluated in a systematic fashion, including a thorough history and physical examination investigating the possibility of a hormone-secreting mass. This includes the possibility of a pheochromocytoma, Cushing’s syndrome, primary hyperaldosteronism, and hypertestosteronemia. Specifically, the patient should be questioned regarding poorly controlled hypertension, diabetes, edema, diaphoresis, tachycardia, palpitations, sudden severe headaches, flushing, and easy bruising. The physical exam should look for evidence of central obesity, edema, peripheral wasting, core muscle weakness, a buffalo hump, striae, thin skin, and facial plethora. Because the adrenal gland is situated in the retroperitoneum, unless it is extremely large, palpation of the mass is usually unable to be achieved.

All adrenal masses should undergo appropriate biochemical testing. Even in the absence of signs or symptoms, patients should have at a minimum: potassium, aldosterone, renin, plasma fractionated metanephrines (followed by 24-hour urine metanephrines and normetanephrines, catecholamines, and vanillylmandelic acid (VMA) if plasma values are abnormal), 24-hour urine-free cortisol, and adrenocorticotropic hormone (ACTH). Some physicians may also perform a low-dose dexamethasone suppression test and obtain dehydroepiandrosterone Sulfate (DHEA-S) and free testosterone, among other laboratory tests.

Imaging studies should include an adrenal protocol computed tomography (CT) scan (to assess imaging characteristics and calculate washout percentage of contrast from the tumor) or magnetic resonance imaging (MRI) (to assess decrease in signal between in and out of phase images) and 18F-Fluorodeoxyglucose (18FDG) positron emission tomography (PET) CT if malignancy is questioned (FIG 1).

Additional imaging studies may be required depending on the functionality of the tumor (metaiodobenzylguanidine [MIBG] for some pheochromocytoma patients, adrenal vein sampling for hyperaldosteronism, etc.).

Fine needle aspiration or core biopsy is not recommended if adrenocortical carcinoma is questioned. FNA may be useful if metastasis to the adrenal gland is in the differential and the adrenal tumor is the most accessible site of metastasis in the setting of multiple sites of metastatic disease. If biopsy is performed, it is imperative to first biochemically rule out pheochromocytoma.

Adrenal tumors, if benign appearing by imaging criteria, nonfunctional, and therefore not requiring resection, should be reevaluated with at least one additional CT scan or MRI 6 to 12 months after the initial imaging study to ensure stability in size and internal imaging characteristics. Some advocate for a longer period of follow-up imaging for 2 years with reevaluation of biochemistry for 4 years.¹

Functional tumors leading to hormone excess, indeterminate masses, and those suspected of being adrenocortical carcinoma or isolated metastatic disease from another primary tumor without evidence of widespread metastatic disease should be removed.