title: Macroprolactinomas in children and adolescents: factors associated with the response to treatment in 77 patients.
abstract: BACKGROUND
  Pituitary adenomas are rare in children and adolescents. The response of macroprolactinomas to dopamine agonists (DA) in this age group has been less extensively studied than in adults.
  
  
  OBJECTIVE
  We retrospectively analyzed data on a large cohort of young patients with macroprolactinomas.
  
  
  METHODS
  Patients aged younger than 20 years at macroprolactinoma diagnosis and seen in three tertiary referral centers between 1983 and 2013 were studied by analyzing their clinical and genetic (AIP and MEN1) characteristics. Hormonal and tumoral responses to DA were analyzed, and the patients' status at their last visit, after a mean (±SD) follow-up of 8.2 ± 5.8 years, was assessed.
  
  
  RESULTS
  The cohort comprised 77 patients (26 males, 51 females). Mean age at diagnosis was 16.1 ± 2.5 years (range, 4.5-20 y). In both sexes, the most frequent revealing symptom was a pubertal disorder (49%), followed by visual problems (24%) and growth retardation (24%). Basal prolactin (PRL) levels and maximal tumor diameter were significantly higher in boys than in girls (7168 ng/mL, 202-40 168 vs 1433 ng/mL, 115-20 000, P = .002; and 33 ± 14 mm, 15-64 vs 19 ± 9 mm; 10-50, P < .001, respectively). PRL levels normalized in 74% of the patients treated with DA. A mutation of AIP or MEN1 was found in 14% of the patients. Factors associated with resistance to DA were young age, higher PRL levels, larger volume, and the presence of a MEN1 (but not an AIP) mutation.
  
  
  CONCLUSIONS
  Macroprolactinomas are rare below the age of 20 years, mainly occurring in girls and during adolescence. Like adults, young patients are very sensitive to DA, which should therefore be considered the first-line treatment. DA resistance is associated with a higher PRL level and larger tumor size, both parameters being closely linked together. About 14% of these young patients have an AIP or MEN1 mutation, this latter being an independent predictor of DA resistance.
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction and Centre de Référence des Maladies Endocriniennes Rares de la Croissance (S.S., T.B., P.K., J.Y., P.C.), and Service de Génétique Moléculaire, Pharmacogénétique, et Hormonologie (J.B., A.G.-M.), and Service d'Endocrinologie Pédiatrique and Centre de Référence des Maladies Rares du Métabolisme Phospho-Calcique, (A.L.), Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin-Bicêtre, F-94275, France; Service d'Endocrinologie (D.A., B.D.) and Service de Pédiatrie (P.-F.S.), Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré, Reims, F-51092, France; Faculté de Médecine (G.R., M.N., F.B.-C.), Université de Lyon, Lyon 1, Lyon-Est, Lyon F-69372 France; Fédération d'Endocrinologie (G.R., F.B.-C.) and Service d'Endocrinologie Pédiatrique (M.N.), Hôpital Femme-Mère-Enfant, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, F-69003, France; Institut National de la Santé et de la Recherche Médicale Unité 1028 (G.R.), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon Neuroscience Research Center, Service de Neurooncology-Neuroinflammation, and INSERM Unité 1052 (F.B.-C.), Unité Mixte de Recherche Centre National de la Recherche Scientifique Unité 5286, Centre de Recherche en Cancérologie de Lyon, Equipe Tumeurs Endocrines, Lyon, F-69000, France; Unité Mixte de Recherche Scientifique Unité 693 (P.K., J.B., A.M., A.L., J.Y., P.C.), Faculté de Médecine Paris-Sud, Université Paris-Sud 11, Le Kremlin-Bicêtre F-94276, France; INSERM Unité 986 (A.L.) and INSERM Unité 693 (P.K., J.B., A.M., J.Y., P.C.), Le Kremlin-Bicêtre F-94276, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Deborah
authors.initials: D
authors.lastname: Ancelle
authors.forename: Thibaut
authors.initials: T
authors.lastname: Bahougne
authors.forename: Gérald
authors.initials: G
authors.lastname: Raverot
authors.forename: Peter
authors.initials: P
authors.lastname: Kamenický
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Souchon
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Delemer
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018491:Dopamine Agonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D011388:Prolactin