Pituitary adenomas are commonly occurring lesions, only some of which will result in clinically significant disease. The underlying molecular changes leading to monoclonal cell proliferation with self-limited growth in the majority of cases, and continuous growth in a small proportion, are currently unknown. While hormonal influences are clearly important additional factors, the primary abnormality will ultimately lead to up-regulation of the cell cycle machinery. Hormonal feedback pathways as well as signal transduction pathways such as the PI3K-Akt-mTOR and Raf-ERK pathways, cell cycle proteins and tyrosine kinase receptors have all been studied both for up/downregulation and for somatic mutations. Another clinically very important approach is studying markers which could be used clinically to predict the behaviour of pituitary adenomas. Although familial pituitary adenomas are rare, the role of germline mutations has been recently recognised in a high percentage of young-onset cases. Finally, although minimal data are available, the role of environmental factors cannot be ruled out.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: This research was supported by The Wellcome Trust (grant numbers 084361, 078432, and 086545).