EFFECTS OF 17 MONTHS TREATMENT USING RECOMBINANT INSULIN-LIKE GROWTH FACTOR-I IN 2 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 mug/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/l), low plasma IGF-1 (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-1 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/l) 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 ug/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.