Intersubject responsiveness of high-affinity growth hormone (GH)-binding protein (GHBP) to long-term GH replacement therapy

In adult growth hormone deficiency (GHD) syndrome responsiveness to GH repl acement therapy is reported to vary considerably. The underlying mechanisms , however, are not well understood. The aim of this study was to investigat e which baseline variables determine the reported variable intersubject res ponsiveness of high-affinity GH-binding protein (GHBP) to GH replacement th erapy. In the setting of a double blind study over 12 months with placebo c ontrol over the first 6 months, we analyzed the interrelationship between a number of baseline variables, which vary considerably amongst subjects, an d the GHBP response to GH replacement in 31 GHD adults (21 males and 10 fem ales). The following variables were investigated: age, gender, duration of GHD, body composition, serum levels of high-affinity GHBP, insulin-like gro wth factor-1 (IGF-1), and IGF-binding protein-3 (IGFBP-3). The results show ed that in the b months treated group of 16 patients (11 males, 5 females), serum IGF-1 increased from 87 ng/ml (range: 26 to 173) to 250 (range: 62 t o 467) (p<0.01) and GHBP increased from 1302 pmol/l (range: 845 to 1960) to 1418 (range: 941 to 2025) (p=0.04). Both parameters showed a significant t ime effect (within-subjects) (p less than or equal to 0.001). In the 12 mon ths treated group of 15 patients (10 males, 5 females), serum IGF-1 increas ed from 92 ng/ml (range: 20 to 180) to 272 (range: 45 to 491) (p<0.01), whe reas GHBP did not show a significant change: from 1186 pmol/l (range: 660 t o 1690) to 1252 (range: 580 to 1890) (p=0.87). Also no significant time eff ect (within-subjects) was observed for GHBP (p=0.06). Stepwise multiple reg ression analyses revealed that during the b months placebo period baseline GHBP explained 83% of the variance in post-placebo GHBP, whereas the varian ce in post-treatment GHBP could be accurately predicted (adjusted R-2=0.93) from baseline GHBP and body fat mass, irrespective of the duration of GH t reatment. No other baseline variables contributed independently to the GHBP response, with the exception of IGFBP3, which showed a small, but signific ant contribution in females, but not in males. These findings indicate that the variable intersubject responsiveness of GHBP to GH replacement therapy is mainly due to differences in baseline body fat mass amongst adult GHD p atients, and that in female patients a relatively low baseline IGFBP-3 cont ributes to a rise in serum GHBP after GH treatment. The clinical relevance of measuring GHBP in adult GHD patients is limited to the first screening s tep to diagnose GHD, because long-term GH therapy tends to restore serum GH BP to pretreatment levels. (C) 2000, Editrice Kurtis .