Landscape of FIPA : AIP and Prospective Diagnosis
Hernández-Ramírez, Laura C. Queen Mary University of London
Gabrovska, Plamena Queen Mary University of London
Dénes, Judit Queen Mary University of London
Stals, Karen Royal Devon and Exeter National Health Service Foundation Trust
Trivellin, Giampaolo Queen Mary University of London|National Institutes of Health
Tilley, Daniel Queen Mary University of London
Ferraù, Francesco Queen Mary University of London
Evanson, Jane Queen Mary University of London
Ellard, Sian Royal Devon and Exeter National Health Service Foundation Trust
Grossman, Ashley B. Churchill Hospital
Roncaroli, Federico Imperial College
Gadelha, Mônica R. Federal University of Rio de Janeiro
Korbonits, Márta Queen Mary University of London
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 previously unrecognized disease.
Objective: To determine the 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: This was an observational, longitudinal study conducted over 7 years.
Setting: International collaborative study conducted at referral centers for pituitary diseases.
Participants: FIPA families (n = 216) and sporadic young-onset (≤30 y) pituitary adenoma patients (n = 404) participated in the study.
Interventions: We performed 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): We assessed 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 with patients with nontruncating 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.Atotal of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 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.
The Journal of Clinical Endocrinology & Metabolism
The Endocrine Society|Oxford University Press
Collaborators : Members of the FIPA consortium are listed at http://www.fipapatients.org/fipaconsortium/.
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).
|DOI (Published Version)|
|URL ( Publisher's Version )|
jcem_100_9_E1242.pdf 522 KB