DIURNAL-VARIATION IN SERUM INSULIN-LIKE GROWTH-FACTOR (IGF)-I AND IGFBINDING-PROTEINS CONCENTRATIONS DURING DAILY SUBCUTANEOUS INJECTIONS OF RECOMBINANT HUMAN GROWTH-HORMONE IN GH-DEFICIENT ADULTS

OBJECTIVE Whereas there seems to be little, if any, circadian variatio n in circulating concentrations of IGF-I and IGFBP-3 in healthy subjec ts, there are conflicting reports on this issue in GH-deficient patien ts treated with GH as a daily subcutaneous injection, We have therefor e investigated the 24-hour serum profiles of IGF-I and IGFBP-3 concent rations after one week and more than one year of GH treatment. PATIENT S Eleven subjects, with adult onset GH deficiency mainly caused by pit uitary adenomas were included in the study. DESIGN AND MEASUREMENTS In an open study, six subjects (three women and three men; age (+/-SEM) 41.2 +/- 3.9 years) were investigated after one week of GH therapy and five subjects (three women and two men; age (+/-SEM) 61.4 +/- 3.3 yea rs) were investigated after 13-40 months of GH therapy, The GH injecti ons were given at 2000 h. The subjects were hospitalized for 24-hour b lood sampling at 1-hour intervals and serum concentrations of GH, IGF- I and IGFBP-3 were determined. RESULTS There was a significant diurnal variation in serum IGF-I and IGFBP-3 concentrations both in the subje cts who had received GH for one week and in those who had received GH treatment for more than one year, The serum concentrations of IGF-I an d IGFBP-3 were highest in the morning and lowest during night-time and early morning, The molar IGF-I/IGFBP-3 ratio varied significantly wit h time in both groups of patients in a similar way as IGF-I and IGFBP- 3 indicating a more pronounced variation in IGF-I compared with IGFBP- 3 in response to the GH therapy, CONCLUSION Significant diurnal variat ions in serum IGF-I and IGFBP-3 concentrations occur after one week an d more than one year of GH treatment with daily subcutaneous injection s, The results indicate that the free fraction of IGF-I may exhibit a diurnal variation.