Major Genetic Motifs in Pituitary Adenomas: A Practical Literature Update

Pituitary adenomas (PAs) are common central nervous system tumors arising from the adenohypophysis of the pituitary gland. They are the second most common intracranial neoplasms following meningiomas.1, 2, 3, 4 PAs have a varying prevalence rate and can be as high as 17%.2,3,5 Often benign and monoclonal, PAs have many different classifications, including clinically significant and silent PAs.1,6, 7, 8 PAs can become clinically apparent secondary to their mass effect and impingement on surrounding neurovascular structures and/or endocrinological derangements due to altered pituitary hormone secretion, the specifics of which are elaborated on below.4,5,8,9 The ability of some PAs to secrete hormones has further helped categorizing these lesions into nonfunctional (non–hormone-secreting) and functional (hormone-secreting) adenomas (Figure 1).

The management paradigm of PAs depends on various factors, including whether the tumor is functional, the patient's age, clinical manifestations, tumor size, and invasion into surrounding structures, among others.1,7,10 While medical therapy is essential in the management of certain PAs (e.g., prolactinomas), surgical resection remains an important modality in the management of PAs through the relief of mass effect and therefore the restoration of normal hormonal regulation.6,8

Although the pathophysiology of PA development and growth remains elusive, various genetic mutations (both germline and sporadic) have been identified as potential culprits. The genetic markers for germline mutation–derived PAs are well characterized in the literature (Figure 2) with several identified biomarkers, including p27Kip1 (p27), p21Cip1 (p21), pituitary tumor-transforming gene (PTTG), CD34, and vascular endothelial growth factor.11 With the genetic discoveries surrounding multiple endocrine neoplasia (MEN) 1 and 4 syndromes, there is new understanding of important genetic mutations and their functions, such as the pivotal role of p27 in causing MEN1- and MEN4-derived PAs.

With the increased understanding of PAs and the molecular/genetic aberrations associated with their development and growth, new therapies are being developed to target these molecular and genetic culprits.2,8 Thus, it becomes essential to understand these molecular and genetic alterations and their implications on PA development and growth. However, despite these initial encouraging results, most of the underlying mutations have not yet been elucidated, as the majority of PAs are sporadic in origin. The goal of this article was to review the genetic underpinnings of PAs to provide a practical clinical understanding and application for scientists and clinicians.9

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