title: Parathyroid hormone-related peptide (PTHrP) secretion by gastroenteropancreatic neuroendocrine tumors (GEP-NETs): clinical features, diagnosis, management, and follow-up.
abstract: BACKGROUND
  Only a small number of case reports has been published on patients with PTHrP-hypersecreting metastatic gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
  
  
  OBJECTIVE
  The objective of this study was to evaluate the clinical, biochemical, and radiological features, management, and treatment outcome of patients with PTHrP-hypersecreting GEP-NETs.
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Tertiary referral hospital.
  
  
  METHODS
  Clinical, biochemical, and radiological features were measured, as well as response to therapy and survival.
  
  
  METHODS
  Ten patients with PTHrP-secreting GEP-NETs (nine pancreatic and one unknown primary) with a median age of 50.4 years (range, 38.3-61.1) were studied. Multiple endocrine neoplasia type 1 patients were excluded.
  
  
  RESULTS
  The median follow-up was 57.2 months (range, 11.6-204.5 mo). Median overall survival was 86.0 months. In total, 51 different treatment interventions and combinations were applied. In seven of the 10 patients, somatostatin analog (SSA) treatment resulted in a temporary normalization of serum calcium levels with a long-term response observed in two patients (up to 35.2 mo). Peptide receptor radiotherapy (PRRT) with radiolabeled SSAs induced long-term responses ranging from 9.0-49.0 months in four of six patients treated with PRRT.
  
  
  CONCLUSIONS
  Hypersecretion of PTHrP by metastatic GEP-NETs is very rare and seems to be exclusively associated with metastatic pancreatic NETs. PTHrP production has major clinical impact because poorly controllable hypercalcemia is associated with increased morbidity and mortality. The most successful treatment options for PTHrP-producing GEP-NETs are SSAs and PRRT using radiolabeled SSAs. Isotonic saline and bisphosphonates can be considered as supportive therapies.
authors.affiliation: Department of Internal Medicine, Sector of Endocrinology (K.K., R.A.F., R.C.S.v.A., W.W.d.H.), Department of Clinical Chemistry (Y.B.d.R.), Department of Pathology (F.H.v.N.), and Department of Nuclear Medicine (D.J.K.), ENETS Centre of Excellence, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kamp
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.forename: Roxanne C S
authors.initials: RC
authors.lastname: van Adrichem
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Francien H
authors.initials: FH
authors.lastname: van Nederveen
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000601:surgery; D015282:Octreotide / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000601:surgery; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D044162:Parathyroid Hormone-Related Protein; D015282:Octreotide