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 IS 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. Hypoglycaemia 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 17μg/L, IGF-I<5th centile, with% increment during IGF-I generation test <20%. IG1411313-3 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, 120μg/kg bid induced a change in mean height velocity from 4.1cm/year before treatment to 10.2cm/year at 6 months and 8.8cm/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.