title: Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor.
abstract: BACKGROUND
  Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to various neoplasms. Endocrine manifestations in PJS include gynecomastia due to calcified Sertoli cell testicular tumors usually referred to as large-cell calcifying Sertoli cell tumors (LSCT).
  
  
  OBJECTIVE
  To evaluate the value of endocrine markers and aromatase inhibitor treatment in children with PJS and LSCT.
  
  
  METHODS
  Familial cases, followed in a tertiary care center.
  
  
  METHODS
  Two male siblings aged 7 and 9 years with PJS and LSCT.
  
  
  METHODS
  Third generation aromatase inhibitor (anastrozole) in one of the patients.
  
  
  METHODS
  Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers and auxological evaluation.
  
  
  RESULTS
  The two male siblings with PJS had similar bilateral multifocal testicular calcifications and biochemical evidence of Sertoli cell dysfunction manifested by elevated plasma inhibin-alpha levels. Only one sibling had gynecomastia. Estradiol levels were normal in both. During treatment with anastrozole, estradiol levels, growth and skeletal maturation, as well as Sertoli cell markers (inhibin B, inhibin-alpha and anti-Mullerian hormone) decreased.
  
  
  CONCLUSIONS
  Inhibin-alpha may be considered as a marker for LSCT in children with PJS, pointing to a specific defect in inhibin regulation in this condition. Moreover, the decrease in Sertoli cell markers during aromatase inhibitor treatment suggests that increased estrogen production is a primary event regulating downstream production of Sertoli cell peptides. Anastrozole is efficient in controlling the clinical features of the disease and should be proposed as an alternative to bilateral orchidectomy, which is often performed in this condition.
authors.affiliation: Department of Pediatric Endocrinology and INSERM U561, Groupe Hospitalier Cochin-Saint Vincent de Paul and Université Paris V, 82 av Denfert Rochereau, 75014 Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefevre
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvattier
authors.forename: Najiba
authors.initials: N
authors.lastname: Lahlou
authors.forename: Catherine
authors.initials: C
authors.lastname: Adamsbaum
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
mesh_terms: D000077384:Anastrozole; D054304:Anti-Mullerian Hormone; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006177:Gynecomastia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007265:Inhibins / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D010375:Pedigree; D019683:Penetrance; D010580:Peutz-Jeghers Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D012707:Sertoli Cell Tumor / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013735:Testicular Hormones / Q000097:blood; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D006023:Glycoproteins; D009570:Nitriles; D013735:Testicular Hormones; D014230:Triazoles; C422364:inhibin B; C094377:inhibin-alpha subunit; D000077384:Anastrozole; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D004247:DNA