title: Circulating serotonin and bone density, structure, and turnover in carcinoid syndrome.
abstract: BACKGROUND
  Gut-derived serotonin has been proposed as a regulator of bone formation, and inhibition of gut serotonin synthesis increases bone formation in rodents. Carcinoid neuroendocrine tumors can produce very high levels of circulating serotonin and so offer a model of serotonin excess in humans.
  
  
  OBJECTIVE
  The objective of the study was to determine whether patients with carcinoid syndrome have lower bone formation markers, lower bone density, or poor bone structure compared with healthy controls.
  
  
  METHODS
  We conducted a cross-sectional study of 25 patients with carcinoid syndrome and 25 healthy controls, individually matched to carcinoid patients by gender, age, height, and body mass index.
  
  
  METHODS
  We measured circulating serotonin in blood and plasma and 5-hydroxyindoleacetic acid (5HIAA) in plasma and urine. We measured lumbar spine and hip bone mineral density by dual-energy x-ray absorptiometry, the distal radius and tibia with high-resolution peripheral quantitative computed tomography, and bone turnover with serum osteocalcin, amino-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX).
  
  
  RESULTS
  All measures of serotonin and 5HIAA were higher in carcinoid patients than in controls. No measures of bone density or bone structure differed significantly between cases and controls. Osteocalcin was higher in the cases than controls (26.0 vs 21.1 ng/mL, P = .02). PINP and CTX did not differ between cases and controls. In patients with carcinoid syndrome, plasma 5HIAA was positively correlated with osteocalcin. In controls, whole-blood serotonin was positively correlated with osteocalcin, PINP, and CTX (R values = 0.40-0.47, all P < .05.).
  
  
  CONCLUSIONS
  High circulating serotonin in carcinoid syndrome is not associated with clinically significant lower bone density, poorer bone structure, or lower bone formation markers.
authors: Academic Unit of Bone Metabolism, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, United Kingdom. jennifer.walsh2@sth.nhs.uk
authors: Jennifer S
authors: JS
authors: Walsh
authors: John D
authors: JD
authors: Newell-Price
authors: Miguel
authors: M
authors: DeBono
authors: Joanne
authors: J
authors: Adaway
authors: Brian
authors: B
authors: Keevil
authors: Richard
authors: R
authors: Eastell
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000652:urine; D008297:Male; D008303:Malignant Carcinoid Syndrome / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism / Q000652:urine; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism / Q000652:urine; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D012701:Serotonin / Q000097:blood*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid
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