PMID- 26186299 OWN - NLM STAT- MEDLINE DCOM- 20151124 LR - 20220317 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 100 IP - 9 DP - 2015 Sep TI - Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers. PG - E1242-54 AB - 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. A total 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. FAU - Hernandez-Ramirez, Laura C AU - Hernandez-Ramirez LC FAU - Gabrovska, Plamena AU - Gabrovska P FAU - Denes, Judit AU - Denes J FAU - Stals, Karen AU - Stals K FAU - Trivellin, Giampaolo AU - Trivellin G FAU - Tilley, Daniel AU - Tilley D FAU - Ferrau, Francesco AU - Ferrau F FAU - Evanson, Jane AU - Evanson J FAU - Ellard, Sian AU - Ellard S FAU - Grossman, Ashley B AU - Grossman AB FAU - Roncaroli, Federico AU - Roncaroli F FAU - Gadelha, Monica R AU - Gadelha MR FAU - Korbonits, Marta AU - Korbonits M CN - International FIPA Consortium LA - eng SI - ClinicalTrials.gov/NCT00461188 GR - 098395/WT_/Wellcome Trust/United Kingdom GR - G0801473/MRC_/Medical Research Council/United Kingdom GR - 097970/Z/11/Z/WT_/Wellcome Trust/United Kingdom GR - G0701307/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (aryl hydrocarbon receptor-interacting protein) RN - Pituitary Adenoma, Familial Isolated SB - IM MH - Adenoma/*diagnosis/genetics/pathology MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Child MH - Child, Preschool MH - Female MH - Genetic Testing MH - Germ-Line Mutation MH - Growth Hormone-Secreting Pituitary Adenoma/*diagnosis/genetics/pathology MH - Humans MH - Intracellular Signaling Peptides and Proteins/*genetics MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Mutation MH - Pituitary Neoplasms/*diagnosis/genetics/pathology MH - Prospective Studies MH - Young Adult PMC - PMC4570169 FIR - Agha, Amar IR - Agha A FIR - Akker, Scott A IR - Akker SA FIR - Aflorei, Elena D IR - Aflorei ED FIR - Alfoldi, Sandor IR - Alfoldi S FIR - Arlt, Wiebke IR - Arlt W FIR - Atkinson, Brew IR - Atkinson B FIR - Aulinas-Maso, Anna IR - Aulinas-Maso A FIR - Aylwin, Simon J IR - Aylwin SJ FIR - Backeljauw, Philippe F IR - 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Storr H FIR - Strasburger, Christian IR - Strasburger C FIR - Street, Maria Elisabeth IR - Street ME FIR - Swords, Francesca IR - Swords F FIR - Thakker, Rajesh V IR - Thakker RV FIR - Tham, Elaine IR - Tham E FIR - Thompson, Chris IR - Thompson C FIR - Thorner, Michael O IR - Thorner MO FIR - Toth, Miklos IR - Toth M FIR - Trainer, Peter J IR - Trainer PJ FIR - Tsagarakis, Stylianos IR - Tsagarakis S FIR - Tzanela, Marinella IR - Tzanela M FIR - Vadasz, Janos IR - Vadasz J FIR - Vaks, Vladimir IR - Vaks V FIR - Verkauskiene, Rasa IR - Verkauskiene R FIR - Wass, John A IR - Wass JA FIR - Webb, Susan M IR - Webb SM FIR - Weber, Astrid IR - Weber A FIR - Yamada, Shozo IR - Yamada S FIR - Yarman, Sema IR - Yarman S FIR - Yeoh, Philip IR - Yeoh P FIR - Yoshimoto, Katsuhiko IR - Yoshimoto K FIR - Zammitt, Nicola N IR - Zammitt NN EDAT- 2015/07/18 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/07/17 CRDT- 2015/07/18 06:00 PHST- 2015/07/18 06:00 [entrez] PHST- 2015/07/18 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/07/17 00:00 [pmc-release] AID - 15-1869 [pii] AID - 10.1210/jc.2015-1869 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2015 Sep;100(9):E1242-54. doi: 10.1210/jc.2015-1869.