Adrenocortical Carcinomas

WHILE ADRENOCORTICAL MASSES are common and occur in up to 15 percent of the adult population, adrenocortical carcinomas (ACs) are much less frequent. In fact, an international estimate of ACs is only one per million each year. However, it is currently not known why the incidence is approximately 10 times higher in southern Brazil. While there is no racial predilection towards this disease, it occurs in females approximately three times more frequently than in males. One of the more common classification schemes for adrenocortical carcinomas is the functional and nonfunctional distinction. Classification of functional tumors is based on the type of hormone that the tissue produces, i.e., mineralocorticoids, glucocorticoids, androgens, estrogens or other peptide hormones. There is generally a bimodal age distribution with functional carcinomas: early childhood and in the fourth to fifth decades of their lives. Nonfunctional carcinomas are more common in adults.

Adrenocortical tumors have been linked to several hereditary cancer syndromes, including multiple endocrine neoplasia type 1 (MEN 1), familial polyposis coli, Turcot syndrome, Beckwith-Wiedmann syndrome, Li-Fraumeni syndrome, Gardner syndrome, the SBLA (sarcoma, breast, lung, and adrenocortical cancer) syndrome and Cowden syndrome. The cause of these syndromes is not yet known, although it has been proposed that tumor suppressor gene (TP53 and TP57 genes) mutations and adrenal hyperplasia may predispose an individual to ACs. Furthermore, protooncogene and defects in apoptosis may be another target, as they also regulate AC development.

Adrenocortical carcinomas may manifest themselves in individuals as symptoms directly related to the tumor mass itself or due to the excessive hormonal production. Nonfunctional tumors often are associated with abdominal pain or fullness, back pain and weight loss. In addition to these symptoms, the individual may also have symptoms related to his/her particular endocrine abnormality. This may include the following:

• Cushing's syndrome
• Feminization
• Primary hyperaldosteronism
• Hirsutism, facial acne, oligomenorrhea or amenorrhea
• Virilization syndromes: virilization in girls, precocious puberty in boys
• Hypertension
• Polycythemia
• Hypercalcemia
• Hypoglycemia
• Insulin resistance
• Catecholamine excess

If an adrenocortical tumor is suspected, computed tomography (CT) scanning or magnetic resonance imaging (MRI) are the preferred imaging modalities. The classic finding of an AC on CT scans is a unilateral mass with irregular borders. MRIs are important when differentiating adrenocortical carcinomas from adenomas. Ultrasounds are less useful for detection, but can be used to follow adrenal incidentalomas.

It is also important to test for abnormal hormone production. Dexamethasone suppression tests and 24-hour urinary cortisol excretion tests can be used to screen for Cushing syndrome. Hyperaldosteronism can be evaluated by measuring aldosterone and renin levels.

Individuals should be tested for levels of adrenal androgens and plasma estradiol to screen for virilization syndromes and feminization syndromes, respectively. The presence of urinary catecholamines helps to establish the presence of a pheochromocytoma.

Once the presence of an adrenocortical carcinoma has been established, the stage of the tumor must be established to guide treatment. Staging for ACs is commonly based on the Sullivan scale, which takes into consideration tumor size, the involvement of lymph nodes, and metastatic disease. Treatments include surgery, chemotherapeutic drugs, and radiation therapy. The definitive treatment for adrenocortical adenomas and carcinomas [Page 7]is surgical management. Surgery is almost always curative for adenomas and provides the best prognosis for carcinomas.

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