The molecular pathogenesis of corticotroph tumours

Eur J Clin Invest 2012; 42 (6): 665676 Abstract Background The pathogenesis of tumour formation in the anterior pituitary including adrenocorticotropic hormone (ACTH)-secreting tumours has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain unclear. Materials and methods We searched PubMed on any paper related with molecular pathology of pituitary corticotroph adenomas and have included to this review all relevant references published up to June 2011. Results Current studies increased our knowledge on the genetic basis of McCuneAlbright syndrome (MAS), multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), pituitary adenoma predisposition syndromes and tuberous sclerosis, but they have performed little to elucidate the causes of sporadic pituitary tumours including Cushing disease. Discussion The aim of this review was to focus on the most recently published advances in the molecular pathology of corticotroph adenomas, which are presented in the context of changes seen in all types of pituitary adenomas, as well as in terms of corticotrophin-releasing hormone/ACTH/cortisol-specific pathways. Conclusions We would expect that over the next 5 years, more detailed analysis of inter-cellular communication pathways between pituitary cells, including the cadherins and integrins, and their interactions with other signalling pathways such as the beta-catenin cascade will help elucidate what exactly goes awry in the formation of a benign corticotroph adenoma. This should in turn predict novel forms of pharmacological tumour control.