Genetics of Familial Acromegaly and Pituitary Gigantism

[en] The subset of pituitary adenomas with a heritable genetic basis is small but clinically striking. Somatotropinomas are amongst the most frequent pituitary adenoma subtypes encountered in this setting, with germline variants being enriched in familial acromegaly kindreds and people with a childhood or adolescent history of GH hypersecretion manifesting as pituitary gigantism.The genetic causes of familial acromegaly and pituitary gigantism include variants in established pituitary adenoma predisposition genes (AIP especially, but also MEN1, CDKN1B, MAX, and PRKAR1A), X-linked acrogigantism due to Xq26.3 microduplications, and McCune-Albright syndrome due to postzygotic gain-of-function GNAS variants. Potential associations include variants in emerging pituitary adenoma predisposition genes including NF1, PRKACB, PAM, and CHEK2. Given the potential for gene-specific therapeutic implications in these diseases, multimodal genetic testing arranged by experienced pituitary subspecialists and conducted in expert, clinically accredited laboratories is needed to fully evaluate the genetic basis of disease. Key investigations include next-generation sequencing, chromosome microarray, and droplet digital polymerase chain reaction.Exploratory research-based genetic testing may help uncover new genetic causes of familial acromegaly kindreds and pituitary gigantism in people with negative results on standard testing, benefiting those being tested as well as advancing our understanding of the heritable basis of somatotropinomas.

Precision for document type :

Review article

Disciplines :

Endocrinology, metabolism & nutrition

Author, co-author :

De Sousa, Sunita M C

Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques

Language :

English

Title :

Genetics of Familial Acromegaly and Pituitary Gigantism

Publication date :

07 April 2026

Journal title :

Journal of Clinical Endocrinology and Metabolism

ISSN :

0021-972X

eISSN :

1945-7197

Publisher :

Oxford University Press, New York, Us ny

Pages :

dgag151

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://doi.org/10.1210/clinem/dgag151

Available on ORBi :

since 09 April 2026

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