DOSE-DEPENDENT RESPONSES IN INSULIN-LIKE GROWTH-FACTORS, INSULIN-LIKE GROWTH 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 therapy is also essential in adult patients with growth hormone deficiency (GHD). There are little data available on the dose requirements for replacement therapy in this age group. In childhood, the growth response to GH therapy can serve as an indicator for the correct replacement dose. Because this indicator does not exist in adults, we analyzed growth factors and biochemical markers of bone metabolism by specific radioimmunoassays 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 treatment 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 levels 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 ng/ml (p less than or equal to 0.01). IGF-binding protein-3 in serum: basal, 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 serum: basal, 113.6 +/- 36.7 mu g/l; low dose, 211.6 +/- 90.4 mu g/l (p less than or equal to 0.01); no further increase. Galactosylhydroxylysine 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 represent 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/week) normalized serum levels of growth factors and parameters of bone metabolism, this dose might be the advisable replacement dose in adult GHD.