Insulin-like growth factor-I treatment in two children with growth hormone gene deletions.

Two unrelated Brazilian patients had homozygous 6.7 kb deletions in the GH-1 gene (girl and boy, 1.8 and 3.3 yr, heights -7.9 and -6.0 SDS, respectively). Desensitization using small amounts of exogenous GH (0.033 IU/kg body weight/week, divided into daily s.c. injections) was attempted, but anti-GH antibodies appeared. Replacement with usual doses of hGH induced only transient increase in growth. IGF-I therapy with increasing doses resulted in catch-up growth without side-effects. Growth velocity was 7.5 cm/yr in the first year and 8.4 cm/yr in the next 6 months in patient 1, and 6.7 cm/yr in the first year, 5.9 cm/yr in the second year and 7.9 cm/yr in the third year of IGF-I treatment in patient 2, when the daily dose of 240 micrograms/kg was divided into three injections. IGFBP-3 levels were low (0.55 and 0.40 mg/I) and did not increase after IGF-I treatment, suggesting that this GH effect is not mediated by IGF-I, and injected IGF-I had a rapid disappearance rate. We conclude that IGF-I promotes growth by endocrine mechanisms and constitutes an effective treatment for patients with GH insensitivity secondary to GH antibodies.