title: Clinical characterization of familial isolated pituitary adenomas.
abstract: BACKGROUND
  Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).
  
  
  OBJECTIVE
  Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA).
  
  
  METHODS
  We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands.
  
  
  RESULTS
  Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases.
  
  
  CONCLUSIONS
  Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium.
authors.forename: A F
authors.initials: AF
authors.lastname: Daly
authors.forename: M-L
authors.initials: ML
authors.lastname: Jaffrain-Rea
authors.forename: A
authors.initials: A
authors.lastname: Ciccarelli
authors.forename: H
authors.initials: H
authors.lastname: Valdes-Socin
authors.forename: V
authors.initials: V
authors.lastname: Rohmer
authors.forename: G
authors.initials: G
authors.lastname: Tamburrano
authors.forename: C
authors.initials: C
authors.lastname: Borson-Chazot
authors.forename: B
authors.initials: B
authors.lastname: Estour
authors.forename: E
authors.initials: E
authors.lastname: Ciccarelli
authors.forename: T
authors.initials: T
authors.lastname: Brue
authors.forename: P
authors.initials: P
authors.lastname: Ferolla
authors.forename: P
authors.initials: P
authors.lastname: Emy
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: E
authors.initials: E
authors.lastname: De Menis
authors.forename: P
authors.initials: P
authors.lastname: Lecomte
authors.forename: F
authors.initials: F
authors.lastname: Penfornis
authors.forename: B
authors.initials: B
authors.lastname: Delemer
authors.forename: J
authors.initials: J
authors.lastname: Bertherat
authors.forename: J L
authors.initials: JL
authors.lastname: Wémeau
authors.forename: W
authors.initials: W
authors.lastname: De Herder
authors.forename: F
authors.initials: F
authors.lastname: Archambeaud
authors.forename: A
authors.initials: A
authors.lastname: Stevenaert
authors.forename: A
authors.initials: A
authors.lastname: Calender
authors.forename: A
authors.initials: A
authors.lastname: Murat
authors.forename: F
authors.initials: F
authors.lastname: Cavagnini
authors.forename: A
authors.initials: A
authors.lastname: Beckers
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D005260:Female; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D006065:Gonadotropins, Pituitary; C517834:PRKAR1A protein, human; D010908:Pituitary Hormones, Anterior; D000324:Adrenocorticotropic Hormone; D017868:Cyclic AMP-Dependent Protein Kinases