PROLONGED TREATMENT WITH RECOMBINANT INSULIN-LIKE GROWTH-FACTOR-I IN CHILDREN WITH GROWTH-HORMONE INSENSITIVITY SYNDROME - A CLINICAL RESEARCH-CENTER STUDY

Eight children with GH insensitivity syndrome, five with GH receptor d eficiency (Laron syndrome) and three with growth-attenuating antibodie s to GH, were treated with recombinant human insulinlike growth factor I(IGF-I) for 24 months (one was treated for 36 months). Their ages at the beginning of therapy ranged from 2-11 yr. The dose of IGF-I range d between 80-120 mu g/kg, given sc twice daily. During the first year of treatment, height velocity (HV) improved in each patient (mean pret reatment HV, 4.0 cm/yr; mean of first year, 9.3 cm/yr). HV declined by 33% during the second year (mean HV, 6.2 cm/yr). The third year HV of the one patient so treated was approximately the same as that in the second year. The mean so score KV before therapy was -2.4 and improved to +3.8 and +0.5 after 1 and 2 yr of therapy, respectively. Increased HV was accompanied by weight gain. IGF-I-related hypoglycemia occurre d infrequently and only early in treatment. No adverse changes in bioc hemical profile were observed. Bone age did not advance more rapidly t han chronological age (mean change in bone age, 2.1 yr; mean change in chronologocal age, 2.2 yr). The growth of the spleen and kidneys (det ermined by ultrasound) was rapid in the first year of therapy. In the second year, spleen growth slowed to a normal rate in most patients. K idney growth, however, remained relatively rapid. These results indica te that IGF-I stimulates statural growth for at least 2 yr and confirm s that this peptide has the capacity to act through endocrine mechanis ms. Prolonged treatment of GH insensitivity syndrome patients shows pr omise. The stimulation of growth by IGF-I treatment over years needs t o be documented, and patients need to be monitored for side-effects.