title: GH sensitivity of GH-deficient adults is dependent on gender     but not timing of onset.
abstract: BACKGROUND
  Females secrete 2-3 -fold greater amounts of GH compared with males despite maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from relative resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and the need for higher GH maintenance doses during replacement. Adults with severe GHD of childhood-onset (CO) have lower basal IGF-I SDS and require higher GH maintenance doses compared with adult-onset (AO) patients with GHD of equal severity. We hypothesised CO-GHD adults to be less sensitive to GH than AO-GHD patients.
  
  
  METHODS
  In a single site study we analysed the incremental change in IGF-I (DeltaIGF-I) in 116 GHD adults following initiation of GH replacement. The data were corrected to provide DeltaIGF-I/mg GH because of slight variances in initial GH dose.
  
  
  RESULTS
  Following GH replacement DeltaIGF-I was 230 +/- 245 and 356 +/- 278 ng/ml/mg GH in females and males, respectively (P = 0.01). In CO and AO patients DeltaIGF-I was 282 +/- 206 and 294 +/- 292 ng/ml/mg GH, respectively (P = 0.83). Further analysis after stratification by both gender and timing of onset of GHD showed DeltaIGF-I was 226 +/- 164, 324 +/- 228, 231 +/- 268, and 373 +/- 304 ng/ml/mg GH in the CO females, CO males, AO females, and AO males, respectively (AO males vs. AO females, P = 0.03; CO males vs. CO females, P = 0.17; AO males vs. CO males, P > 0.05; AO females vs. CO females, P > 0.05). Multiple linear regression with DeltaIGF-I as the dependent variable and age, gender, BMI, baseline IGF-I level, and timing of onset as independent variables showed DeltaIGF-I to be dependent on gender alone (R = 0.28, P = 0.004). Age (P = 0.44), BMI (P = 0.54), baseline IGF-I level (P = 0.63) and timing of onset (P = 0.61) had no effect on DeltaIGF-I.
  
  
  CONCLUSIONS
  We have shown gender to have a significant impact on GH sensitivity in GHD adults, which, at least in part, explains differences in maintenance dosages during replacement. None of the additional variables impacted significantly on GH sensitivity. The lower basal IGF-I SDS and higher GH replacement requirement reported in CO compared with AO patients cannot be explained by differences in sensitivity to GH.
authors.affiliation: Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: Breeda
authors.initials: B
authors.lastname: Columb
authors.forename: Linda E
authors.initials: LE
authors.lastname: Smethurst
authors.forename: Annice
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Andreas
authors.initials: A
authors.lastname: Jostel
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone