Carcinomas may arise in the adrenal cortex (adrenocortical carcinoma [ACC]) or the adrenal medulla (malignant pheochromocytomas). Metastatic cancer from other sites may also be seen.

Approximately 60% secrete steroid hormones; about 40% are nonfunctioning.

A functioning ACC secretes cortisol, androgens, estrogens, or aldosterone—alone or in combination. Cortisol overproduction is most common (∼45%) and results in Cushing syndrome. Androgen secretion (∼25%) causes hirsutism and virilization in women and precocious puberty in children but is often asymptomatic in men. Estrogen production causes menstrual disturbances in women and gynecomastia and hypogonadism in men. Excess aldosterone secretion causes hypertension and hypokalemia (Conn syndrome) (Fig. 29-1).

A nonfunctioning ACC manifests clinically as abdominal or flank pain or as an adrenal mass discovered on physical examination or incidentally during an imaging procedure.

Computed tomography (CT) is the method of choice to determine the size and physical characteristics of the mass. Features that most strongly suggest ACC are size greater than 6 cm, heterogeneity, calcifications, irregular borders, local invasion, lymphadenopathy, and decreased lipid content. The last feature is assessed by signal attenuation, expressed in Hounsfield units (HU). An adrenal mass CT protocol is employed in many institutions; this consists of a non-contrast CT, a contrast-enhanced CT, a delayed contrast-enhanced CT, and calculation of the relative washout percentage (RWP) of enhancement. Table 29-1 shows the typical CT findings for some commonly seen adrenal masses. MRI can also be used to assess the size, features, and lipid content of adrenal masses but is more expensive. Fluorodeoxyglucose (¹⁸F) positron emission tomography (FDG-PET) or PET-CT fusion scanning may also be useful, especially for masses with high HU or low RWP on CT. High sensitivities and specificities have been reported with this technique using a standard uptake value (SUV) cutoff of 3.1. Other PET tracers, such as metomidate 11^C, may offer even better sensitivity in the future.

The goal is to determine whether the mass is producing hormones that may cause symptoms or that may be indicative of malignancy (androgens). Many experts recommend a focused evaluation consisting of an overnight 1-mg dexamethasone suppression test, measurement of plasma free metanephrines or fractionated urinary catecholamines and metanephrines, and, for hypertensive patients, measurement of plasma aldosterone and renin. Tests currently recommended by the European Network for the Study of Adrenal Tumors (ENSAT) are shown in Table 29-2.

Surgery is often recommended for tumors larger than 4 cm, for those showing significant growth on follow-up, and for those with evidence of excessive cortisol, androgen, estrogen, aldosterone, or catecholamine secretion. Nonfunctioning adrenal masses smaller than 4 cm should be reassessed in 6 months and then annually thereafter.