The endocrinologist dedicated to the studies of pituitary adenomas is surprised when confronted by the highly variable biological appearance of pituitary tumours. By immunohistochemistry and in situ hybridization, pituitary tumours are frequently composed of cells able to co-secrete hormonal molecules with completely different biochemical and biological activities, such as GH/alpha-subunit, PRL/alpha-subunit or GH/TSH, together with normally differentiated cells. This phenomenon is particularly surprising taking into account the recent discovery that the great majority of pituitary tumours are monoclonal in origin. In addition, the frequent detection of allelic deletions of different chromosomes in sporadic pituitary adenomas suggests loss of tumour suppressor genes in these neoplasia. Recent findings also show mutations which result in the constitutive activation of GTP-binding proteins in subsets of pituitary adenomas and a pathogenetic role has been envisaged for gsp and ras oncogenes which are expressed in pituitary tumours with variable frequency.
The latest example of the above