Genetic mutations in sporadic pituitary adenomas—what to screen for?

Abstract

Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.

Symptomatic Occlusion of Internal Carotid Artery Caused by Pituitary Macro Adenoma Among the Patients Without Apoplectic Signs; Case Report and Review of the Literature

“…It has demonstrated that invasion of the cavernous sinus by tumors might lead to the compression and occlusion of the internal carotid artery (ICA) (4). The consequence of this event would be the presence of various clinical manifestations (4). On the other hand, the prevalence of pituitary adenomas has increased in the last few years (5).…”

“…If they have grown to larger sizes they might result in compression with surrounding structures including cavernous sinus (2,3). It has demonstrated that invasion of the cavernous sinus by tumors might lead to the compression and occlusion of the internal carotid artery (ICA) (4). The consequence of this event would be the presence of various clinical manifestations (4).…”

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

“…MEN1-gén-mutációt a sporadikus daganatok 0,6-2,6%-ában, AIP-mutációt nagyjából a 3%-ukban, GNAS1-mutációt pedig a növekedési hormont termelő daganatok 27-43%-ában találnak szöveti szinten [9][10][11].…”

Gene mutations in Cushing's disease

“…Recent studies have demonstrated that mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene, and Carney complex and multiple endocrine neoplasia type 1 (MEN1) are associated with sporadic PAs (6,7). Disruption in the balance of pituitary-secreting hormones as a result of gene mutation may result in severe-to-fatal consequences.…”