ADRENOCORTICAL ADENOMA AND CARCINOMA
Adrenocortical Tumours are rare (incidence approximately 0.2 per 100,000 per year) and may be benign or malignant. The most frequent presentation is with Cushing syndrome with or without associated virilization, sometimes with primary aldosteronism; estrogen-producing Tumours are rare. Adrenocortical carcinomas are proven component cancers in Li–Fraumeni syndrome caused by germline TP53 mutations. Indeed, early-onset (under the age of 4 years) or bilateral disease carries a high likelihood of germline TP53 mutation (Malkin et al. 1990; Eng et al. 1997). In a series of 14 patients with adrenocortical carcinoma unselected for family history, 11 (82%) carried a germline TP53 mutation.
Interestingly, the same two mutations (at codons 152 and 158) were present in 9 of the 11 mutation-positive cases. In another series of 36 cases of childhood adrenocortical carcinoma in southern Brazil, 35 carried an identical R337H mutation (Ribeiro et al. 2001). Some believe that adrenocortical carcinomas can be found at increased frequencies in Beckwith–Wiedemann syndrome (Wiedemann 1983).
A macroscopically and histologically distinctive type of adrenocortical hyperplasia called primary pigmented nodular adrenocortical disease (PPNAD) is a component neoplasia of CNC (NAME syndrome). PPNAD can be clinically diagnosed by its paradoxical response to dexamethasone challenge (Stratakis et al. 1999). Benign adrenocortical lesions, usually nonfunctional, are reported in MEN 1 patients, some believe as frequently as 20–40 %. Adrenocortical nodular hyperplasia and rarely adenoma may be seen in McCune–Albright syndrome. Hypercortisolism is often associated with macronodular hyperplasia of the adrenal cortex. Recently, germline variation in PDE11 has been associated with macronodular hyperplasia of the adrenal cortex (Horvath et al. 2006).