Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias

Nat Clin Pract Endocrinol Metab. 2007 Nov;3(11):748-57. doi: 10.1038/ncpendmet0648.


Adrenocortical causes of Cushing's syndrome include the following: common cortisol-producing adenomas, which are usually isolated (without associated tumors) and sporadic (without a family history); rare, but often clinically devastating, adrenocortical carcinomas; and a spectrum of adrenocorticotropin-independent, and almost always bilateral, hyperplasias, which are not rare, and are the most recently recognized cause. The majority of benign lesions of the adrenal cortex seem to be linked to abnormalities of the cyclic AMP signaling pathway, whereas cancer is linked to aberrant expression of insulin-like growth factor II, tumor protein p53 and related molecules. In this article, we propose a new clinical classification and nomenclature for the various forms of adrenocorticotropin-independent adrenocortical hyperplasias that is based on their histologic and genetic features. We also review the molecular genetics of adrenocortical tumors, including recent discoveries relating to the role of phosphodiesterase 11A. This is a timely Review because of recent advances in the clinical and molecular understanding of these diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adrenal Cortex Diseases / classification
  • Adrenal Cortex Diseases / complications
  • Adrenal Cortex Diseases / genetics
  • Adrenal Cortex Diseases / pathology
  • Adrenal Cortex Neoplasms / classification
  • Adrenal Cortex Neoplasms / complications
  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / pathology
  • Adrenal Gland Neoplasms / classification*
  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / pathology
  • Animals
  • Cushing Syndrome / classification*
  • Cushing Syndrome / complications
  • Cushing Syndrome / genetics*
  • Cushing Syndrome / pathology
  • Humans
  • Hyperplasia / classification
  • Hyperplasia / genetics
  • Hyperplasia / pathology