Effects of 17 months treatment using recombinant insulin-like growth factor-I in two children with growth hormone insensitivity (Laron) syndrome

OBJECTIVE With the availability of recombinant insulin-like growth factor-I (recIGF-I), it was possible to study whether this peptide could promote growth without noticeable side-effects in patients with growth hormone insensitivity syndrome (Laron syndrome). We report data obtained before and during 17 months treatment using recIGF-I, 40 μg/kg s.c. twice a day, in two Lebanese siblings. PATIENTS The boy and the girl showed very short stature (-6.8 and ?6.1 SDS), high GH (79 and 147 IU/I), low plasma IGF-I (0.12 and 0.18 U/ml) and undetectable GH-binding protein. Height velocities were 4.3 and 3.8 cm/year before treatment which started at 8.4 and 6.8 years of age, respectively. RESULTS After 1–8 weeks of therapy, biological evidence of IGF-I effect was obtained from reduction in serum GH and increase in procollagen-I. During the first 6 months of treatment, height velocity increased to 7.8 and 8.4 cm/year without any clinical evidence of side-effects. Between 6 and 12 months, growth response decreased to 6.6 and 6.3 cm/year. Between 12 and 17 months, growth rate returned to pretreatment values. Changes in bone mineral density paralleled growth response and bone maturation increased by 1 5 and 2 0 years during the first 12 months of treatment. Daily assessment of blood sugar showed asymptomatic low values (< 2 8 mM/I) in 11/730 and 22/730 measurements in the boy and the girl, respectively. CONCLUSIONS Treatment of two patients with growth hormone insensitivity syndrome using 40 μ g/kg of IGF-I twice a day resulted in increased linear bone growth and bone mineralization as well as increased bone maturation without remarkable adverse events. After 1 year of therapy, growth response could no longer be observed in these two patients.