Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa

Exaggerated GH and reduced insulin-like growth factor I (IGF-I) level are c ommon features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback could account, in part, for GH hypersecretion. To ascertain this, we studied the effects of recombinant human (rh)IGF-I on spontaneous and GH -releasing hormone (GHRH)-stimulated GH secretion in nine women with AN [bo dy mass index, 14.1 +/- 0.6 kg/m(2)] and in weight matched controls (normal weight). Mean basal GH concentrations (mGHc) and GHRH (2.0 mug/kg, iv) sti mulation were significantly higher in AN. rhIGF-I administration (20 mug/kg , sc) significantly reduced mGHc in AN (P < 0.01), but not normal weight, a nd inhibited peak GH response to GHRH in both groups; mGHc and peak GH, how ever, persisted at a significantly higher level in AN. Insulin, glucose, an d IGFBP-1 basal levels were similar in both groups. rhIGF-I inhibited insul in in AN, whereas glucose remained unaffected in both groups. IGFBP-1 incre ased in both groups (P < 0.05), with significantly higher levels in AN. IGF BP-3 was under basal conditions at a lower level in AN (P < 0.05) and remai ned unaffected by rhIGF-I. This study demonstrates that a low rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH secret ion in AN, pointing also to the existence of a defective hypothalamic contr ol of GH release. Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in AN.