Pathogenesis of pituitary tumors

  • Melmed S
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Abstract

Multifactorial mechanisms participate in the complex steps leading to pituitary tumor formation (Fig. 2). These include early chromosomal mutations that probably result in release of pituitary stem cells from growth inhibition. Activating genetic mutations occurring proximal to growth factor dysfunction have also been identified. The transformed pituitary cell undergoes clonal expansion and is subsequently subjected to the growth stimuli of several permissive factors, including hypothalamic hormone receptor signals, intrapituitary growth factors, and disordered cell cycle regulation, which all determine the ultimate biologic fate of the tumor. This cascade of events results in autonomous anterior pituitary hormone production and secretion and cell proliferation, which are the hallmarks of pituitary adenomas. Rarely, malignant transformation and metastasis formation may be associated with a secondary oncogenic (ras) transformation in a small subset of pituitary adenomas. Although subcellular events preceding the formation of most secreting and nonfunctional pituitary adenomas have not yet been elucidated, several recent observations have underscored the role of early activating events in most adenomas.

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Authors

  • Shlomo Melmed

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