Adrenocortical carcinoma (ACC) is the most likely cause of this patient's Cushing syndrome, and surgical excision is the most appropriate management. The patient has classic clinical manifestations of Cushing syndrome (CS), and the 24-hour urine cortisol is markedly elevated on repeated measurements. Plasma adrenocorticotropic hormone (ACTH) is suppressed consistent with an ACTH-independent cause. The imaging characteristics of ACC include a large mass with irregular borders or shape, calcification, high attenuation (high Hounsfield units) on CT, and delay in contrast medium washout (less than 50% at 10 minutes), findings all present in this patient.

The treatment of ACC depends on the extent of disease at presentation. Surgical removal after appropriate biochemical assessment remains the best option, especially in patients with early disease. Even after apparent complete resection, adjuvant therapy with mitotane, a known adrenal cytotoxic drug, may be beneficial. Treatment with mitotane is recommended for patients with persistent disease and others with known metastases and is associated with objective remissions in approximately 25% of patients. The main factors limiting the use of mitotane include nausea, vomiting, lethargy, and neurologic side effects. Experience with other cytotoxic chemotherapy is limited, but has usually been ineffective. A poorer prognosis is associated with advanced stages of the disease, the presence of metastasis at diagnosis, an older age, and cortisol hypersecretion by the tumor. In patients without clinically evident disease after initial surgery, the median survival rate is 60% at 5 years.

Fine-needle biopsy cannot distinguish a benign adenoma from a carcinoma and is not used in the evaluation of ACC. It is sometimes used to distinguish ACC from metastatic disease. Its use in this patient is both unnecessary and inappropriate.

Radiation therapy is not used as the principal initial treatment in ACC; however, it may be used as adjuvant therapy after surgery to prevent tumor recurrence. Radiation therapy can also be used to treat areas of metastasis, such as to the bones or brain.