Long-Term Monitoring of Treatment with Recombinant Human Growth Hormone by Serial Determinations of Type III Procollagen-Related Antigens in Serum

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Abstract
Inasmuch as recombinant human growth hormone is now more generally available for the treatment of different types of short stature, there is a need for better short-term indicators of treatment success. In healthy children, serum concentrations of antigens related to the aminoterminal propeptide of type III procollagen (P-III-NP) closely follow the growth velocity curve. P-III-NP was measured longitudinally in 20 children with growth hormone deficiency during 6 months of human growth hormone substitution therapy. Two different radioimmuno-assay systems were used; one recognizes predominantly the intact propeptide showing a lesser affinity to a smaller monomeric peptide (RIAgnost assay), while the other assay detects both forms equally (FAB assay). These results were compared to the growth response [median 5.6 (0.4 to 13.9) cm in 6 months] and to other established growth correlated parameters (somatomedin C, alkaline phosphatase). A relatively better growth response correlated significantly with high pretreatment P-III-NP (RIAgnost assay) values (r = 0.56) and delayed bone age (r = −0.70). A combination of these parameters in multiple regression analysis increased the cumulative prediction value to above 60% (r2 = 0.61). On the other hand, P-III-NP (FAB assay) values proved to be best in monitoring treatment, correlating with the individual growth rate during the first 3 months (r = 0.40; p < 0.05), during the consecutive 3 months (r = 0.66; p < 0.001), and during the total 6-months period (r = 0.46; p < 0.05). All other parameters showed associations to growth only during some treatment periods. Ease of measurement and good correlation with the growth response support the use of the P-III-NP determination in monitoring of human growth hormone therapy.