title: IGF-I bioactivity better reflects growth hormone deficiency than total IGF-I.
abstract: BACKGROUND
  GH is considered the main regulator of circulating IGF-I. Total (extractable) IGF-I is therefore routinely used for diagnosis of GH deficiency (GHD) and for monitoring treatment. Methods currently used for measurement of circulating total IGF-I may be hampered by interferences of IGF-binding proteins. Recently a kinase receptor activation assay was developed to determine IGF-I bioactivity in human serum. The principle of this assay is based on quantification of IGF-I receptor activation after stimulation with serum in vitro.
  
  
  OBJECTIVE
  The objective of the study was to investigate the diagnostic potential of IGF-I bioactivity in adults with GHD.
  
  
  METHODS
  This was a single-center observational study.
  
  
  METHODS
  Ninety-four GH-untreated patients diagnosed with GHD by GH-provocative tests were included.
  
  
  METHODS
  IGF-I bioactivity (determined by the IGF-I kinase receptor activation assay) and total IGF-I (determined by immunoassay) were measured in fasting blood samples.
  
  
  RESULTS
  IGF-I bioactivity was more frequently below the normal range (<-2 sd) in untreated GH-deficient patients than total IGF-I levels (81.9 vs. 61.7%, respectively), especially in patients older than 40 years of age. IGF-I bioactivity decreased with the duration of GHD, whereas total IGF-I did not. With a decreasing number of additional pituitary deficits, total IGF-I levels more frequently remained within the normal range, whereas the percentage below the normal range was high for IGF-I bioactivity, independent of additional deficits.
  
  
  CONCLUSIONS
  Determination of IGF-I bioactivity may offer advantages in the evaluation of adult GHD compared with total IGF-I as bioactivity better reflects GHD as defined by GH stimulation tests, especially in subjects older than 40 years of age.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Varewijck
authors.forename: S W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: P
authors.initials: P
authors.lastname: Uitterlinden
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: J A M J L
authors.initials: JA
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I