The Molecular Genetics of Corticotroph Tumours

Abstract

Cushing disease caused by adrenocorticotropin ‐secreting pituitary adenomas leads to hypercortisolaemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity and increased mortality. Previous studies have enhanced our knowledge on the genetic basis of familial pituitary adenomas, including the McCune–Albright syndrome, multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), Carney complex, the MEN1‐like phenotype (MEN4), pituitary adenoma predisposition syndromes and tuberous sclerosis. These studies, however, have done little to elucidate the causes of sporadic pituitary tumours, including Cushing disease.

We summarise the information available on the molecular derangements of corticotroph tumours, including the most recent advances in the molecular genetics of sporadic lesions, which were published after the latest review on this topic written in 2011. We have left for further reading information about silent corticotroph adenomas, as well as plurihormonal expressing adenomas. We also suggest that more general literature for the readers who want to broaden their knowledge on the molecular biology in general of pituitary adrenomas.

Key Concepts:

  • Some 5% of pituitary adenomas are familial.

  • Previous studies have enhanced our knowledge on the genetic basis of familial pituitary adenomas including the McCune–Albright syndrome (MAS), multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), Carney complex (CNC), the MEN1‐like phenotype (MEN4), pituitary adenoma predisposition (PAP) syndromes and tuberous sclerosis (TSC).

  • These studies, however, have done little to elucidate the causes of sporadic pituitary tumours, including Cushing disease.

  • Molecular studies on pituitary tumours have shown that alterations in the best known tumour suppressor genes in other neoplasms (e.g. P53, RB, etc.) or common oncogenes (e.g. the Ras‐familly) are only rarely involved in the development of these tumours.

  • Silent corticotroph adenomas (SCA) are rare pituitary tumours that are immunoreactive for ACTH, but without clinical evidence of Cushing disease, and tend to show aggressive features.

  • Future work should focus on understanding the molecular mechanisms that control pituitary tumour transformation, where intracellular signalling molecules will constitute not only diagnostic/prognostic markers but also novel therapeutic targets.

Keywords: genetics; corticotroph adenoma; molecular pathogenesis; familial; sporadic

Figure 1.

Selective molecular alterations in pituitary ACTH‐omas.

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Dworakowska, Dorota, and Grossman, Ashley B(Jul 2014) The Molecular Genetics of Corticotroph Tumours. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024906]