SERUM-FREE INSULIN-LIKE GROWTH-FACTOR-I IN GROWTH HORMONE-DEFICIENT ADULTS BEFORE AND AFTER GROWTH-HORMONE REPLACEMENT

The objective of the present study was to compare fasting levels of fr ee IGP-I in serum from patients with adult onset growth hormone defici ency (GHD) and from healthy volunteers, and to examine the effect of G H replacement therapy in GHD on serum free IGF-I, Free IGF-I was measu red using separation of free IGF-I by ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with GHD, in the latter be fore and after 1 year of treatment with GH (2 IU/m(2)) (n=13 or placeb o (n=14). Free IGF-I was significantly decreased in patients with GHD (700 +/- 100 ng/l (mean +/- S.E.M.). range 55-2618 ng/l) compared with controls (1010 +/- 70 ng/l, range 231-2431 ng/l: P=0.0016), Total IGF -I was 85 +/- 10 mu g/l (GHD) and 160 +/- 10 mu g/l (controls) (P < 0. 0001). The ratio of free over total IGF-T was increased in GHD to 0.85 +/- 0.08% compared with 0.66 +/- 0.05% in controls (P = 0.04), In bot h GHD and controls, free IGF-I correlated significantly (P < 0.05% wit h total IGF-I (GHD r=0.78; controls r=0.42), IGFBP-1 (GHD r=-0.67; con trols r=-0.46) and the molar ratio of total IGF-I over IGFBP-3 (GHD r= 0.58; controls r=0.62), After 1 year of GH treatment, free IGF-I was i ncreased to 2780 +/- 320 ng/l (P = 0.003) and total IGF-I was increase d to 270 +/- 30 mu g/l (P = 0.006) both of which values were greater t han those in healthy volunteers, There were no changes in free or tota l IGF-I in the placebo-treated group, In conclusion, levels of free IG F-I are decreased in GHD, but measurements of free IGF-I in a single, fasting serum sample do not offer a better separation of patients with GHD from individuals with normal GH status than can be achieved by me asurement of total IGF-I. One year of treatment with 2 IU/m(2) GH caus ed an increase of serum free ICF-I to supraphysiological levels.