title: Serum and plasma 5-hydroxyindoleacetic acid as an alternative to 24-h urine 5-hydroxyindoleacetic acid measurement.
abstract: BACKGROUND
  Neuroendocrine tumours are slow growing tumours known to secrete a variety of vasoactive peptides which give rise to symptoms of the carcinoid syndrome. The diagnosis and monitoring of patients with neuroendocrine tumours is undertaken in many centres using 24 h urinary measurement of 5-hydroxyindoleacetic acid. However, 5-hydroxyindoleacetic acid can also be quantified in plasma and serum.
  
  
  METHODS
  We measured 5-hydroxyindoleacetic acid concentration in 134 paired EDTA plasma and urine samples from 108 patients with known neuroendocrine tumours and 26 healthy volunteers. We also compared 5-hydroxyindoleacetic acid concentrations in paired serum and plasma samples (n = 63), then analysed paired urine and serum samples (n = 97). Furthermore, we examined the impact of renal impairment on serum 5-hydroxyindoleacetic acid by analysing 5-hydroxyindoleacetic acid in patients without neuroendocrine tumours in different stages of chronic kidney disease, as indicated by the estimated glomerular filtration rate.
  
  
  RESULTS
  Plasma and urine 5-hydroxyindoleacetic acid had very similar diagnostic sensitivities and specificities, with areas under the curve on ROC analysis of 0.917 and 0.920, respectively. Serum and plasma 5-hydroxyindoleacetic acid values showed good correlation but serum results demonstrated a positive bias, indicating the necessity for different serum and plasma reference intervals. There was an inverse correlation between estimated glomerular filtration rate and serum 5-hydroxyindoleacetic acid concentration, with 5-hydroxyindoleacetic acid increasing once the estimated glomerular filtration rate falls below 60 mL/min/1.73 m(2).
  
  
  CONCLUSIONS
  The measurement of both serum and plasma 5-hydroxyindoleacetic acid can be used for the diagnosis and monitoring of patients with neuroendocrine tumours. Provided renal function is taken into consideration, either of these tests should be incorporated into standard practice as an alternative assay to urinary 5-hydroxyindoleacetic acid.
authors.affiliation: Department of Clinical Biochemistry, University Hospital South Manchester NHS Foundation Trust, Manchester, UK The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK jo.adaway@uhsm.nhs.uk.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Adaway
authors.affiliation: Department of Obesity and Endocrinology, University Hospital Aintree and University of Liverpool, Liverpool, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Academic Unit of Bone Metabolism, The University of Sheffield, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Walsh
authors.affiliation: Department of Obesity and Endocrinology, University Hospital Aintree and University of Liverpool, Liverpool, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.affiliation: Christie Pathology Partnership, The Christie NHS Foundation Trust, UK.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Monaghan
authors.affiliation: Department of Endocrinology, The Christie NHS Foundation Trust, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Trainer
authors.affiliation: The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK Department of Medical Oncology, The Christie NHS Foundation Trust, UK.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of Clinical Biochemistry, University Hospital South Manchester NHS Foundation Trust, Manchester, UK The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Keevil
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002275:Carcinoid Heart Disease / Q000097:blood / Q000175:diagnosis / Q000652:urine; D002276:Carcinoid Tumor / Q000097:blood / Q000175:diagnosis / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D006897:Hydroxyindoleacetic Acid
keywords: 5-hydroxyindoleacetic acid; Neuroendocrine tumour; liquid chromatography-tandem mass spectrometry; sensitivity; specificity