title: Metachronous hormonal syndromes in patients with pancreatic neuroendocrine tumors: a case-series study.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described.
  
  
  OBJECTIVE
  To describe MHSs in patients with sporadic PNETs.
  
  
  METHODS
  Retrospective, multicenter study.
  
  
  METHODS
  4 French referral centers.
  
  
  METHODS
  Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014.
  
  
  METHODS
  Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling.
  
  
  RESULTS
  Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs.
  
  
  CONCLUSIONS
  Retrospective data collection and heterogeneity of pathologic specimen size and origin.
  
  
  CONCLUSIONS
  Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates.
  
  
  BACKGROUND
  None.
authors.forename: Louis
authors.initials: L
authors.lastname: de Mestier
authors.forename: Olivia
authors.initials: O
authors.lastname: Hentic
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cros
authors.forename: Thomas
authors.initials: T
authors.lastname: Walter
authors.forename: Guillaume
authors.initials: G
authors.lastname: Roquin
authors.forename: Hedia
authors.initials: H
authors.lastname: Brixi
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombard-Bohas
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.forename: Marie-Danièle
authors.initials: MD
authors.lastname: Diebold
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cadiot
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005755:Gastrins / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D013577:Syndrome; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005755:Gastrins; D006728:Hormones; D007328:Insulin; D019394:Ki-67 Antigen; D014660:Vasoactive Intestinal Peptide; D005934:Glucagon