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Horm Metab Res 2020; 52(08): 553-561
DOI: 10.1055/a-1143-5930
Review

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas

Vladimir Vasilev
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
2   Department of Endocrinology, Medical University, Sofia, Bulgaria
,
Adrian F. Daly 
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
,
Sabina Zacharieva
2   Department of Endocrinology, Medical University, Sofia, Bulgaria
,
Albert Beckers
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
› Institutsangaben Funding: This work was supported by grants from the JABBS Foundation, UK and the Fonds d’Investissement Pour la Recherche Scientifique (FIRS), CHU de Liège, Belgium
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Abstract

Pituitary adenomas are benign tumors with variable functional characteristics that can have a significant impact on patients. The majority arise sporadically, but an inherited genetic susceptibility is increasingly being recognized. Recent advances in genetics have widened the scope of our understanding of pituitary tumorigenesis. The clinical and genetic characteristics of pituitary adenomas that develop in the setting of germline-mosaic and somatic GNAS mutations (McCune–Albright syndrome and sporadic acromegaly), germline MEN1 mutations (multiple endocrine neoplasia type 1), and germline PRKAR1A mutations (Carney complex) have been well described. Non-syndromic familial cases of isolated pituitary tumors can occur as familial isolated pituitary adenomas (FIPA); mutations/deletions of the AIP gene have been found in a minority of these. Genetic alterations in GPR101 have been identified recently as causing X-linked acro-gigantism (X-LAG) leading to very early-onset pediatric gigantism. Associations of pituitary adenomas with other tumors have been described in syndromes like multiple endocrine neoplasia type 4, pheochromocytoma-paraganglioma with pituitary adenoma association (3PAs) syndrome and some of their genetic causes have been elucidated. The genetic etiologies of a significant proportions of sporadic corticotropinomas have recently been identified with the discovery of USP8 and USP48 mutations. The elucidation of genetic and molecular pathophysiology in pituitary adenomas is a key factor for better patient management and effective follow-up.

Key words

pituitary adenoma - GNAS - AIP - USP8 - MEN1 - GPR101 - Carney complex - X-LAG - FIPA


Publikationsverlauf

Eingereicht: 14. August 2019

Angenommen: 11. März 2020

Artikel online veröffentlicht:
16. April 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

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