The Cytogenesis and Pathogenesis of Pituitary Adenomas*

Abstract

PITUITARY tumors are common neoplasms that exhibit a wide range of biological behavior, in terms of hormonal and proliferative activities. Their hormonal activity is usually reflective of their cytodifferentiation. The adenohypophysis is a complex gland composed of several cell types that are responsible for the production of many hormones. It was once believed that one cell could make only one hormone (1); the concept of plurihormonality in pituitary adenomas was once controversial and poorly understood. However, advances in our recognition of the factors that regulate cell differentiation in the adenohypophysis have led to a new classification of adenohypophysial cell types (2) and a more sophisticated understanding of the mechanisms that determine the patterns of hormone production in pituitary adenomas. For many years there has been controversy regarding the basis of pituitary tumorigenesis. Two prevailing theories have pitted hormonal stimulation against an intrinsic pituitary defect. Several animal models have provided support for the role of hormonal stimulation in the development of these neoplasms, and there is evidence for adenohypophysial production of hypothalamic hypophysiotropic hormones that may be responsible for excess stimulation. Other growth factors have also been shown to cause pituitary tumors. In contrast, the clonal nature of pituitary adenomas and the lack of associated hyperplasia in most patients with pituitary adenomas argue for a molecular defect as the etiology of these lesions. An integrated approach reconciles the two proposed theories of tumorigenesis by applying the multistep theory of carcinogenesis. It is likely that the majority of pituitary adenomas develop from transformed cells that are, nevertheless, dependent on hormonal and/or growth factor stimulation for tumor progression, which will be discussed below.