Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults: I. Effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis.
Recombinant human growth hormone (GH) is routinely administered as daily subcutaneous injections to patients with GH deficiency (GHD). However, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on longitudinal bone growth, serum insulin-like growth factor-I (IGF-I) concentrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well-documented GH-dependent factors. Recombinant human GH (0.25 U/kg/wk) was administered to nine men with GHD for 14 days in two different ways, ie, as a daily subcutaneous injection at 8 PM and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. An oral glucose tolerance test (OGTT) was performed on day 0 and day 14. Daily injections and continuous infusion of GH exerted similar effects in terms of body weight and body composition. The two modes of administration resulted in similar daily urinary GH excretion and similar serum GH concentrations in the morning. GH binding protein (GHBP) concentrations did not change significantly during the various treatment periods. Serum IGF-I and IGF-I binding protein (IGFBP)-3 concentrations increased to a greater degree during continuous infusion of GH versus daily injections. Serum IGFBP-I concentrations decreased to a similar degree during the two modes of administration. Serum concentrations of free triiodothyronine and total triiodothyronine (T3) increased and free thyroxine (T4) decreased to a similar degree, independent of the mode of administration. However, total T4 concentrations were unchanged during both modes of treatment. Serum thyrotropin (TSH) concentrations decreased during continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels increased during treatment with only daily injection of GH, but there was no significant effect from continuous infusion. Results of measurements of fasting concentrations of blood glucose and oral glucose tolerance (OGT) indicated a more impaired glucose tolerance after daily injections of GH versus continuous infusion. In conclusion, continuous infusion and daily injections of GH have similar effects on the variables described, but the magnitude of the effects differs.
Johansson
J O
JO
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg University, Sweden.
Oscarsson
J
J
Bjarnason
R
R
Bengtsson
B A
BA
D000328:Adult; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood
D005230:Fatty Acids, Nonesterified; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D013006:Growth Hormone; D005947:Glucose