Growth Hormone Insensitivity Syndrome (GHIS); Clinical Presentation and Effects of Treatment with Recombinant Human Insulin-like Growth Factor I (rhIGF-I) European Experience

Growth hormone insensitivity syndrome (GHIS) is a pathological state characterised by disturbance of the normal relationships between growth hormone (GH) secretion, insulin-like growth factor I (IGF-I) synthesis and GH action. Laron syndrome (LS) is the most severe form and is related to defects of the GH receptor gene. Twenty-seven cases of LS from 8 European countries and Australia were characterised clinically and endocrinologically. Clinical features (median) were; age 2.8-22.6 years, 12 males, 15 females, birth weight-0.72 SDS, birth length-1.59 SDS. Hypoglycemia occurred in 33 % and micropenis in 58 % of males. Height was-6.0 SDS, weight-3.2 SDS, % weight for height 111.3. Bone age was delayed in 19 of the 27 patients. Endocrine values (median) were; GH 17 [igL, IGF-I < 5th centile, with % increment during IGF-I generation test < 20%. IGFBP-3 was < 5th centile, GH-BP was low or undetectable in 20 and normal in 7 subjects. Treatment with recombinant IGF-I offered the only form of effective therapy. Treatment of 13 patients with IGF-I, 120 (ig/kg bid induced a change in mean height velocity from 4.1 cm/year before treatment to 10.2 cm/year at 6 months and 8.8 cm/year at 12 months. Adverse effects were minimal. Facial appearance showed a change in maturity associated with capital hair growth. Further studies to define the optimum dose regimen of IGF-I are in progress.