title: Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours.
abstract: BACKGROUND
  As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage.
  
  
  OBJECTIVE
  The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients.
  
  
  METHODS
  This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail.
  
  
  RESULTS
  In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P < .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively.
  
  
  CONCLUSIONS
  Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course.
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Crona
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Norlén
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Antonodimitrakis
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Welin
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stålberg
authors.affiliation: Departments of Medical Sciences (J.C., P.A., S.W., B.E.) and Surgical Sciences (O.N., P.S.), Uppsala University, 75185 Uppsala, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007421:Intestine, Small / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D010187:Pancreatic Hormones / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D007328:Insulin; D010187:Pancreatic Hormones