Silent and incidentally detected adrenocortical neoplasms are the most frequent abnormality
of the adrenal cortex. The prevalence of these lesions in the general population is
around 1%, increases with age and reaches 6% in the seventh decade of life. Primary
adrenocortical carcinoma, on the other hand, a highly malignant tumor, is rare with
an incidence of 1.7 cases per million per year. Recent progress has been achieved
in the understanding of adrenocortical tumorigenesis by mapping and identification
of genes responsible for hereditary tumor syndromes like the Li-Fraumeni syndrome,
Beckwith-Wiedemann syndrome, Carney complex and the Multiple Endocrine Neoplasia Type
I. Investigation of the clonal composition of adrenal tumors demonstrates that adrenal
carcinomas are generally monoclonal, whereas adrenal adenoma may be polyclonal in
approximately 25% of cases. These adenomas may have a multicellular origin under the
putative action of extra-adrenal and local growth factors. Oncogenes and tumor suppressor
genes involved in adrenal carcinomas include mutations in the p53 tumor suppressor
gene and rearrangements of the chromosomal locus 11 p15.5 associated with IGF II hyperexpression.
Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not
play a role in adrenal tumor formation. Conversely, deletions of the ACTH receptor
gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical
carcinomas. This indicates that the signaling pathways responsible for adrenocortical
tumor formation are different from that of other endocrine neoplasms like pituitary
and thyroid adenomas.
Key words
Adrenocortical Adenoma - Adrenocortical Carcinoma - Oncogene - Tumor Suppressor Gene
- Tumorigenesis - Steroidogenesis
