ID 109656
Author
Hernández-Ramírez, Laura C. Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Gabrovska, Plamena Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Dénes, Judit Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Stals, Karen Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust
Trivellin, Giampaolo Program on Developmental Endocrinology and Genetics, Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)
Tilley, Daniel Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Ferraù, Francesco Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Evanson, Jane Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
Ellard, Sian Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust
Grossman, Ashley B. Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital
Roncaroli, Federico Division of Brain Sciences, Faculty of Medicine. 11L07b Laboratory Block, Charing Cross Hospital, Imperial College
Gadelha, Mônica R. Endocrinology Unit, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro
Korbonits, Márta Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
The International FIPA Consortium
Keywords
FIPA
AIP
acromegaly
gigantism
genetic screening
prospective diagnosis
Content Type
Journal Article
Description
Context : Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify unapparent disease.
Objective : To determine AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members.
Design : Observational, longitudinal study, 2007-2013.
Setting : International collaborative study, referral centers for pituitary diseases.
Participants : FIPA families (n=216) and sporadic young-onset (≤30 years) pituitary adenoma patients (n=404).
Interventions : Genetic screening of patients for AIPmuts, clinical assessment of their family members and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.
Main Outcome Measure(s) : Clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1 and FGFR4 analysis.
Results : Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared to patients with non-truncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut positive individuals. A total of 164 AIPmut positive unaffected family members were identified; pituitary disease was detected on 18 of those who underwent clinical screening.
Conclusions : A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut positive pituitary adenomas.
Journal Title
The Journal of clinical endocrinology & metabolism
ISSN
0021972X
NCID
AA00695484
Volume
100
Issue
9
Start Page
E1242
End Page
E1254
Sort Key
1242
Published Date
2015-09
Remark
Copyright © 2015 by the Endocrine Society
This article has been published under the terms of the Creative Commons Attribution
License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
EDB ID
Published Source
The Journal of clinical endocrinology & metabolism (2015) Vol.100, No.9 p.E1242-E1254 (doi: 10.1210/jc.2015-1869)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
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