Molecular genetic testing in the management of pituitary disease

Abstract

Objective Most pituitary tumours occur sporadically without a genetically identifiable germline abnormality, a small but increasing proportion present with a genetic defect that predisposes to pituitary tumour development, either isolated (e.g., aryl hydrocarbon receptor‐interacting protein, AIP) or as part of a tumour‐predisposing syndrome (e.g., multiple endocrine neoplasia (MEN) type 1, Carney complex, McCune‐Albright syndrome or pituitary tumour and paraganglioma association). Genetic alterations in sporadic pituitary adenomas may include somatic mutations (e.g., GNAS, USP8). In this review, we take a practical approach: which genetic syndromes should be considered in case of different presentation, such as tumour type, family history, age of onset and additional clinical features of the patient. Design Review of the recent literature in the field of genetics of pituitary tumours. Results Genetic testing in the management of pituitary disease is recommended in a significant minority of the cases. Understanding the genetic basis of the disease helps to identify patients and at‐risk family members, facilitates early diagnosis and therefore better long‐term outcome and opens up new pathways leading to tumorigenesis. Conclusion We provide a concise overview of the genetics of pituitary tumours and discuss the current challenges and implications of these genetic findings in clinical practice.

Genetics of Cushing’s disease: from the lab to clinical practice

“…Cushing’s disease is very rare in genetic syndromes, such as, multiple endocrine neoplasia 1 ( MEN1 encoding for menin), MEN4 ( CDKN1B encoding for the cell cycle inhibitor p27/Kip1) and Carney complex ( PRKAR1A encoding for type 1 alpha regulatory subunit of the cAMP-dependent protein kinase A) (reviewed in [ 2 , 3 ]). Similarly, it is very rarely found in patients with familial isolated pituitary adenomas (FIPA).…”

“…MSH2 , MSH6 and PMS2 ). Although pituitary tumors are seldom, when present they are often invasive corticotroph tumors or carcinomas (reviewed in [ 3 ]).…”

A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study

“…The mechanisms underlying pituitary tumorigenesis are still largely unknown. A small proportion of tumors (~5%) are due to germline mutations, as part of syndromic diseases or as familial isolated pituitary adenomas [ 3 , 4 ]. These tumors are usually more aggressive, may present at a younger age, have a larger tumor size, show increased invasiveness, and are often resistant to standard treatments [ 5 ].…”

Editorial for Clinical Endocrinology special issue on “Genetics in Endocrinology”

“…2 Caroline Pieterman and Gerlof Valk provide a contemporary update on the management of Multiple Endocrine Neoplasia type 1 3 and Márta Korbonits and Eva Coopmans deliver a detailed overview of the genetics of pituitary tumours. 4 Kevin Colclough and colleagues outline a comprehensive approach to the diagnosis of Maturity Onset Diabetes of the Young. 5 Bettina Winzeler and colleagues provide original data and a review of the literature outlining the utility of somatic sequencing platforms in the clinical management of phaeochromocytoma and paraganglioma.…”

“…Paul Newey and colleagues provide expert practical guidance on the approach to variants of uncertain significance 2 . Caroline Pieterman and Gerlof Valk provide a contemporary update on the management of Multiple Endocrine Neoplasia type 1 3 and Márta Korbonits and Eva Coopmans deliver a detailed overview of the genetics of pituitary tumours 4 …”