COLLAGEN METABOLITES IN THE PREDICTION OF RESPONSE TO GH THERAPY IN SHORT CHILDREN

To evaluate the role of collagen metabolites in the prediction of the response to GH treatment we measured the serum concentrations of the C -terminal propeptide of type I procollagen (PICP) and the N-terminal p ropeptide of type LII procollagen (PIIINP) with specific RIAs in 35 sh ort children (16 boys) before and after 5 days, 5 weeks and 3 months o f GH therapy. The mean age of the children was 10.3 years (range 1.9-1 6.4 years) and the bone age ranged from 1.2 to 12.5 years (mean 7.6 ye ars), The initial mean relative height (RHI) was -3.6 SDS (range -6.6 to -2.4s.D.). Nineteen children were found to have GK deficiency (GHD; peak GH responses in two pharmacological tests <10 mu g/l), while the remaining 16 were considered to have undefined short stature (USS). T he children were treated with recombinant human GH (O.1U/kg given subc utaneously at bedtime 6-7 times/week). The increases in RHI over the f irst 6 and 12 months of therapy were used as response measures. There was already a significant increase (P < 0.001) in both the serum PICP and PIIINP levels at 5 days, and the concentrations continued to rise up to 3 months, PICP levels rising less than the PIIINP levels, In the whole group the RHI over 6 months correlated most strongly with the a bsolute PICP concentrations at 3 months (r(s)=0.59; P < 0.05), while t he absolute PIIINP concentrations at 3 months showed the strongest rel ation to the one year RHI (r(s) = 0.69; P < 0.001). In the GHD group t he 6 month RHI was most strongly related to the absolute PICP concentr ation at 3 months (r(s) = 0.59; P < 0.05). In the USS group the absolu te PICP concentrations at 3 months correlated most strongly with the o ne year RHI (r(s) = 0.82; P < 0.01). Significant correlations were als o observed between the absolute PIIINP levels at 3 months and the 6 mo nth RHI (r(s) = 0.60; P < 0.05) and 12 month RHI (r(s) = 0.76; P < 0.0 1) in this group. These results show that GK therapy results in an une quivocal increase in circulating concentrations of PICP and PIIINP. Th e serum PICP and PIIINP concentrations may be of value in the predicti on of the long-term response to GH therapy.