Serum free insulin-like growth factor-I in growth hormone-deficient adults before and after growth hormone replacement

Abstract

The objective of the present study was to compare fasting levels of free IGF-I in serum from patients with adult onset growth hormone deficiency (GHD) and from healthy volunteers, and to examine the effect of GH replacement therapy in GHD on serum free IGF-I. Free IGF-I was measured using separation of free IGF-I by ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with GHD, in the latter before and after 1 year of treatment with GH (2 IU/m2) (n = 13) or placebo (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 micrograms/l (GHD) and 160 +/- 10 micrograms/l (controls) (P < 0.0001). The ratio of free over total IGF-I was increased in GHD to 0.85 +/- 0.08% compared with 0.66 +/- 0.05% in controls (P = 0.04). In both GHD and controls, free IGF-I correlated significantly (P < 0.05) with total IGF-I (GHD r = 0.78; controls r = 0.42), IGFBP-1 (GHD r = -0.67; controls 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 increased to 2780 +/- 320 ng/l (P = 0.003) and total IGF-I was increased to 270 +/- 30 micrograms/l (P = 0.006) both of which values were greater than those in healthy volunteers. There were no changes in free or total IGF-I in the placebo-treated group. In conclusion, levels of free IGF-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 measurement of total IGF-I. One year of treatment with 2IU/m2 GH caused an increase of serum free IGF-I to supraphysiological levels.