DOSE-DEPENDENT RESPONSES IN INSULIN-LIKE GROWTH-FACTORS, INSULIN-LIKEGROWTH FACTOR-BINDING PROTEIN-3 AND PARAMETERS OF BONE METABOLISM TO GROWTH-HORMONE THERAPY IN YOUNG-ADULTS WITH GROWTH-HORMONE DEFICIENCY

There is increasing awareness that growth hormone (GH) replacement the rapy is also essential in adult patients with growth hormone deficienc y (GHD). There are little data available on the dose requirements for replacement therapy in this age group. In childhood, the growth respon se to GH therapy can serve as an indicator for the correct replacement dose. Because this indicator does not exist in adults, we analyzed gr owth factors and biochemical markers of bone metabolism by specific ra dioimmunoassays in a group (n = 12) of adult patients (age, 20.0-31.6 years) with GHD with childhood onset before and after a 4-week treatme nt period (daily, s.c.) with recombinant, human GH at different doses (0.125, 0.25 and 0.5 IU/kg body weight/week). Comparing the basal leve ls to those on low-dose GH (0.125 IU/kg/week) and on a high dose (0.5 IUlkglweek), the following results were obtained. Insulin-like growth factor-I (IGF-I) in serum: basal, 68.6 +/- 37 ng/ml; low dose, 176.9 /- 65 ng/ml (p less than or equal to 0.05); high dose, 380.6 +/- 200 n g/ml (p less than or equal to 0.01). IGF-binding protein-3 in serum: b asal, 2.13 +/- 0.58 mg/l; low dose, 3.23 +/- 0.84 mg/l (p less than or equal to 0.01); high dose, 3.97 +/- 0.82 mg/l. Osteocalcin in serum: basal, 3.88 +/- 1.27 ng/ml; low dose, 7.01 +/- 2.20 ng/ml (p less than or equal to 0.01); no further increase. Procollagen-I peptide in seru m: basal, 113.6 +/- 36.7 mu g/l; low dose, 211.6 +/- 90.4 mu g/l (p le ss than or equal to 0.01); no further increase. Galactosylhydroxylysin e excretion in urine: basal, 12.9 +/- 5.24 mu mol/g; low dose, 23.3 +/ - 13.2 mu mol/g (p less than or equal to 0.05); high dose, 27.7 +/- 13 .7 mu mol/g. We conclude that the parameters measured possibly represe nt a useful tool for the assessment of the correct replacement dose in adult GHD. As the lowest dose investigated (0.125 IU/kg body weight/w eek) normalized serum levels of growth factors and parameters of bone metabolism, this dose might be the advisable replacement dose in adult GHD.