title: Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides.
abstract: OBJECTIVE
  Circulating insulin-like growth factor (IGF)-II and IGF binding protein-2 (IGFBP-2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF-II and IGFBP-2 distributions between acromegalics and a large normal adult population to explore possible determinants.
  
  
  METHODS
  Sixty acromegalic patients undergoing screening colonoscopy (age range 25-81 years); normative data from 306 healthy adults (age range 20-89 years).
  
  
  METHODS
  Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t-tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r).
  
  
  RESULTS
  For acromegalic patients, GH was significantly correlated with IGF-I (r = 0.50; P < 0.001) and IGFBP-3 (r = 0.29; P = 0.03) but not IGF-II or IGFBP-2. Contrary to expectations, mean IGF-II and IGFBP-2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) microg/l and 305 (200, 410) microg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF-II and IGFBP-2. The (IGF-I + IGF-II)/IGFBP-3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP-3 were not linear: as IGFBP-3 increased, IGF-I also increased whereas IGF-II initially increased but then decreased. IGFBP-2 did not correlate with IGF-II, but molar concentration significantly correlated with the IGF-II/IGFBP-3 molar ratio (r = 0.40; P = 0.001).
  
  
  CONCLUSIONS
  Serum IGF-II and IGFBP-2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF-I + IGF-II)/IGFBP-3 molar ratio appears to be pivotal in determining IGF-II values, which, in turn, expressed as a ratio of IGFBP-3, is related to IGFBP-2. These observations offer new insights into the regulation of these peptides.
authors.affiliation: Department of Surgery, Christie Hospital NHS Trust, Manchester, UK. arenehan@picr.man.ac.uk
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
authors.forename: A A
authors.initials: AA
authors.lastname: Toogood
authors.forename: W D
authors.initials: WD
authors.lastname: Ryder
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: C S
authors.initials: CS
authors.lastname: Potten
authors.forename: S T
authors.initials: ST
authors.lastname: O'Dwyer
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000150:complications; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000150:complications; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008875:Middle Aged; D012044:Regression Analysis
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II