title: Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was an observational, longitudinal study conducted over 7 years.
  
  
  METHODS
  International collaborative study conducted at referral centers for pituitary diseases.
  
  
  METHODS
  FIPA families (n 216) and sporadic young-onset (30 y) pituitary adenoma patients (n 404) participated in the study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Hernández-Ramírez
authors.forename: Plamena
authors.initials: P
authors.lastname: Gabrovska
authors.forename: Judit
authors.initials: J
authors.lastname: Dénes
authors.forename: Karen
authors.initials: K
authors.lastname: Stals
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.forename: Daniel
authors.initials: D
authors.lastname: Tilley
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrau
authors.forename: Jane
authors.initials: J
authors.lastname: Evanson
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Federico
authors.initials: F
authors.lastname: Roncaroli
authors.forename: Mónica R
authors.initials: MR
authors.lastname: Gadelha
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein