title: Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome.
abstract: BACKGROUND
  Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer.
  
  
  RESULTS
  We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma.
  
  
  CONCLUSIONS
  Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. © 2016 S. Karger AG, Basel.
authors.affiliation: UPMC Univ Paris 06, Sorbonne Universités, Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Brioude
authors.forename: Carole
authors.initials: C
authors.lastname: Nicolas
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marey
authors.forename: Stephan
authors.initials: S
authors.lastname: Gaillard
authors.forename: Michèle
authors.initials: M
authors.lastname: Bernier
authors.forename: Cristina
authors.initials: C
authors.lastname: Das Neves
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Bouc
authors.forename: Philippe
authors.initials: P
authors.lastname: Touraine
authors.forename: Irene
authors.initials: I
authors.lastname: Netchine
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism; D003480:Cushing Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D056426:Genetic Loci; D006801:Humans; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D056827:Endosomal Sorting Complexes Required for Transport; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D010450:Endopeptidases; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase