Pituitary adenomas are a heterogeneous group of
tumors that may occur as part of a complex syndrome or as an isolated endocrinopathy and both forms can be familial or non-familial. Studies of syndromic and non-syndromic
pituitary adenomas have yielded important insights about the molecular mechanisms underlying
tumorigenesis. Thus, syndromic forms, including
multiple endocrine neoplasia type 1 (MEN1), MEN4,
Carney Complex and
McCune Albright syndrome, have been shown to be due to mutations of the
tumor-suppressor protein menin, a
cyclin-dependent kinase inhibitor (p27Kip1), the
protein kinase A regulatory subunit 1-α, and the
G-protein α-stimulatory subunit (Gsα), respectively. Non-syndromic forms, which include
familial isolated pituitary adenoma (FIPA) and sporadic
tumors, have been shown to be due to abnormalities of: the
aryl hydrocarbon receptor-interacting protein; Gsα; signal transducers; cell cycle regulators; transcriptional modulators and
miRNAs. The roles of these molecular abnormalities and epigenetic mechanisms in pituitary
tumorigenesis, and their therapeutic implications are reviewed.