title: Individual igf-I responsiveness to a fixed regimen of low-dose growth hormone replacement is increased with less variability in obese compared to non-obese adults with severe growth hormone deficiency.
abstract: OBJECTIVE
  Decreased GH and IGF-I levels and increased GH responsiveness are frequently reported in obesity. As GH-deficient adults are commonly obese, the role of obesity in affecting hepatic responsiveness of IGF-I generation to GH stimulation is unclear in severe GH-deficient states. To address this question, we challenged a cohort of severely GH-deficient non-obese and obese adults with a fixed low GH dose (0.2 mg/day), and examined the relationship of body mass index (BMI) with IGF-I response.
  
  
  METHODS
  12 non-obese (6 males, median BMI 24.7 kg/m2) and 14 obese (7 males, median BMI 45.2 kg/m2) adults with severe GH deficiency were studied for 8 weeks. Blood samples were collected at baseline, and weeks 4 and 8.
  
  
  RESULTS
  There was a larger increment and reduced variability of IGF-I levels in obese compared to non-obese GH-deficient adults at week 8, but not at week 4. A similar but smaller increment and less variability was observed with IGFBP-3. Increment IGF-I positively correlated with baseline BMI at weeks 4 (r=0.49, p<0.02) and 8 (r=0.47, p<0.02). No gender differences were observed with the IGF-I and IGFBP-3 response.
  
  
  CONCLUSIONS
  This study demonstrates that there is a larger increment and deceased individual variability of IGF-I to the low GH replacement dose in obese compared to non-obese adults with severe GH deficiency, regardless of gender. The positive association of IGF-I increment with BMI implies a greater impact of obesity rather than GH deficiency in enhancing hepatic sensitivity to GH. These findings, thus, question the reliability of interpreting single serum IGF-I levels in non-obese adults with severe GH deficiency treated with low GH replacement doses.
authors.affiliation: Department of Endocrinology, Addenbrooke's Hospital, Cambridge, UK, and Division of Endocrinology, Oregon Health and Science University, Portland 97239-3098, USA.
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: David M
authors.initials: DM
authors.lastname: Cook
authors.forename: Elease E
authors.initials: EE
authors.lastname: Rumbaugh
authors.forename: Marie B
authors.initials: MB
authors.lastname: Cook
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D002352:Carrier Proteins / Q000097:blood; D015331:Cohort Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies
chemical_list: D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D020155:3-Hydroxybutyric Acid