title: Neuroendocrine tumours of the small bowel: interpretation of raised circulating chromogranin A, urinary 5 hydroxy indole acetic acid and circulating neurokinin A.
abstract: BACKGROUND
  Neuroendocrine tumours (NETs) of the small bowel are difficult to diagnose as symptoms are non-specific and more often found in common gastrointestinal diseases. Chromogranin A (CGA), urinary 5 hydroxy indole acetic acid (U-5HIAA) and Neurokinin A (NKA) are used as laboratory diagnostic tests but results may be misleading or confusing.
  
  
  OBJECTIVE
  To clarify the relevance of NET biomarkers for diagnosis of small bowel NETs.
  
  
  METHODS
  A review of laboratory test results.
  
  
  METHODS
  We reviewed 500 consecutive raised plasma CGA, U-5HIAA and plasma NKA, results from patients in N Ireland. The diagnosis of NET was confirmed by the Northern Ireland Cancer Registry.
  
  
  RESULTS
  In 500 specimens recording raised CGA, 52.2% were from patients with NETs, 13.6% being small bowel tumours, 5.4% of specimens from patients with auto-immune atrophic gastritis and 15.4% from patients taking proton pump inhibitors. In 500 specimens with raised U-5HIAA, 87.8% were from patients with NETs, 68.2% being small bowel tumours. Lung NETs contributed 12.2% and NETs from other sites, 7.4%. Of 500 specimens with raised NKA (reference range (RR) > 20 ng/L), 72.6% were from patients with small bowel NETs and 6% specimens from patients with other NETs. In 20% of specimens NKA concentrations were 21-23 ng/L, within limits of assay precision.
  
  
  CONCLUSIONS
  CGA remains the best general circulating marker for NETs although only half of raised test results are due to an NET. U-5HIAA is an excellent marker for small bowel and lung NETs with 80% of high test results confirming these diagnoses. NKA is the most specific biomarker for small bowel NETs.
authors.affiliation: From the Regional Regulatory Peptide Laboratory, Kelvin Building, NET Specialist Group, Royal Victoria Hospital Belfast NHS Trust, Belfast BT12 6BA, Northern Ireland, UK, Queen's University Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK and Joy.ardill@qub.ac.uk.
authors.forename: J E S
authors.initials: JE
authors.lastname: Ardill
authors.affiliation: From the Regional Regulatory Peptide Laboratory, Kelvin Building.
authors.forename: L
authors.initials: L
authors.lastname: Armstrong
authors.affiliation: Clinical Biochemistry, Kelvin Building, Royal Victoria Hospital Belfast NHS Trust, Belfast BT12 6BA, Northern Ireland, UK.
authors.forename: M
authors.initials: M
authors.lastname: Smye
authors.affiliation: Clinical Biochemistry, Kelvin Building, Royal Victoria Hospital Belfast NHS Trust, Belfast BT12 6BA, Northern Ireland, UK.
authors.forename: R
authors.initials: R
authors.lastname: Doherty
authors.affiliation: NET Specialist Group, Royal Victoria Hospital Belfast NHS Trust, Belfast BT12 6BA, Northern Ireland, UK, Queen's University Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK and.
authors.forename: D R
authors.initials: DR
authors.lastname: McCance
authors.affiliation: NET Specialist Group, Royal Victoria Hospital Belfast NHS Trust, Belfast BT12 6BA, Northern Ireland, UK, Queen's University Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK and.
authors.forename: B T
authors.initials: BT
authors.lastname: Johnston
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D053379:Chromogranin A / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D007414:Intestinal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D015288:Neurokinin A / Q000097:blood*; D009660:Northern Ireland / Q000453:epidemiology; D012042:Registries; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D006897:Hydroxyindoleacetic Acid; D015288:Neurokinin A