Females release 23 fold greater GH compared with males whilst maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and higher GH maintenance doses during replacement. GHD adults of childhood- (CO) and adult-onset (AO) show CO-GHD adults to have lower basal IGF-I values and require higher maintenance doses. We hypothesised CO-GHD adults are less sensitive to GH than AO-GHD patients.
We analysed the incremental change in IGF-I (ΔIGF-I) in 114 GHD adults following initiation of GH replacement. The data were corrected to provide ΔIGF-I/mgGH due to slight variances in initial GH dose. Following GH replacement ΔIGF-I was 356±278 and 230±245 ng/ml/mgGH in females and males respectively (P=0.003). In CO and AO patients ΔIGF-I was 282±206 and 285±287 ng/ml/mgGH respectively (P=0.71). Further analysis after stratification by gender and timing of onset of GHD showed ΔIGF-I was 226±164, 324±228, 216±250, and 373±308 ng/ml/mgGH in the CO females, CO males, AO females, and AO males respectively (AO males vs AO females, P<0.05; 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 ΔIGF-I as the dependent variable and age, gender, BMI, baseline IGF-I level, and timing of onset as independent variables showed ΔIGF-I to be dependent on gender alone (R=0.28, P=0.004). Age (P=0.44), BMI (P=0.56), baseline IGF-I level (P=0.64) and timing of onset (P=0.63) had no effect on ΔIGF-I.
We showed gender has 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 and higher GH requirement in CO patients remains unexplained.