title: Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study.
abstract: BACKGROUND
  AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.
  
  
  OBJECTIVE
  The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas.
  
  
  METHODS
  This study was an international, multicenter, retrospective case collection/database analysis.
  
  
  METHODS
  The study was conducted at 36 tertiary referral endocrine and clinical genetics departments.
  
  
  METHODS
  Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls.
  
  
  RESULTS
  The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy.
  
  
  CONCLUSIONS
  AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium.
authors.forename: Adrian F
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authors.lastname: Daly
authors.forename: Maria A
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authors.lastname: Petrossians
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authors.lastname: De Menis
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authors.lastname: Montañana
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authors.forename: Juliet
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authors.lastname: Labarta Aizpún
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authors.lastname: Georgitsi
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authors.lastname: Valimaki
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authors.lastname: De Herder
authors.forename: Renato
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authors.lastname: Cozzi
authors.forename: Mirtha
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authors.lastname: Guitelman
authors.forename: Flavia
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authors.lastname: Magri
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authors.lastname: Lagonigro
authors.forename: Georges
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authors.lastname: Halaby
authors.forename: Vinciane
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authors.lastname: Corman
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Hagelstein
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Vanbellinghen
authors.forename: Gustavo Barcelos
authors.initials: GB
authors.lastname: Barra
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Cameron
authors.forename: Françoise
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authors.lastname: Borson-Chazot
authors.forename: Ian
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authors.lastname: Holdaway
authors.forename: Sergio P A
authors.initials: SP
authors.lastname: Toledo
authors.forename: Günter K
authors.initials: GK
authors.lastname: Stalla
authors.forename: Anna
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authors.lastname: Spada
authors.forename: Sabina
authors.initials: S
authors.lastname: Zacharieva
authors.forename: Jerome
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authors.lastname: Bertherat
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
authors.forename: Vincent
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authors.lastname: Bours
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mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000367:Age Factors; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists