The effect of recombinant IGF‐I on anterior pituitary function in healthy volunteers

Summary OBJECTIVE Insulin‐like growth factor‐I is the mediator of many of the actions of GH and is a potent metabolic regulator. Recombinant IGF‐I (rhIGF‐I) is of potential value in the treatment of syndromes associated with either GH or insulin resistance. This study was designed to assess the effects of subcutaneous (s.c.) rhIGF‐I on anterior pituitary function. DESIGN Double‐blind, placebo controlled, randomized cross‐over study. The interval between investigations was 2 weeks. SUBJECTS Twelve normal volunteers received on one occasion a single S.C. dose of 40 μg/kg rhIGF‐I and on the other, placebo. MEASUREMENTS Circulating levels were measured, over 24 hours, of GH, LH, FSH, PRL, TSH, cortisol, ACTH, glucose, IGF‐I, IGF‐II, Insulin, C‐peptide; IGF binding proteins by Western ligand blotting; total IGF bioactivity using FRTL‐5 thyroid cells; and glucose by the glucose oxidase method. RESULTS Recombinant IGF‐I Increased AUC for plasma IGF‐I, measured by radioimmunoassay (rhIGF‐I mean 7065 ± SEM 33 vs 3895 ± 204 μg/l, P < 0·0001) and IGF bioactivity (22·5 ± 3·4 vs 14·2 ± 1·8 U/ml, P < 0·001) but plasma IGF‐II fell (9308 ± 403 vs 11052 ± 451 μg/l, P < 0·0001). There was no biochemical or clinical evidence of hypoglycaemia and no difference in mean glucose levels. No difference existed in AUC for GH, LH, FSH, ACTH and cortisol between rhIGF‐I and placebo; additionally, pulse number and amplitude for GH and LH were unaffected. TSH fell following rhIGF‐I (33·0 ± 3·36 vs 42·5 ± 5·98 mU h/l, P = 0·01). Both mean plasma C‐peptlde (0·73 ± 0 06 vs 0·91 ± 0±05 nmol/l, P = 0·03), and insulin (10·81 ± 1·02 vs 15·36 ± 1·18 mU/l, P = 0·03) were lower following rhIGF‐I. There was no change In IGFBPs. CONCLUSION A single injection of 40 μg/kg of subcutaneous rhIGF‐I does not cause hypoglycaemia. IGF bioactivity was increased without inhibition of GH secretion. The only change observed in anterior pituitary function was a fall in plasma TSH.