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 fac tor-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 obtai ned 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 gir l showed very short stature (-6.8 and -6.1 SDS), high GH (79 and 147 I U/l), low plasma IGF-1 (0.12 and 0.18 U/ml) and undetectable GH-bindin g 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 Afte r 1-8 weeks of therapy, biological evidence of IGF-1 effect was obtain ed from reduction in serum GH and increase in procollagen-I. During th e 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 maturatio n increased by 1.5 and 2.0 years during the first 12 months of treatme nt. 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, r espectively. CONCLUSIONS Treatment of two patients with growth hormone insensitivity syndrome using 40 ug/kg of IGF-I twice a day resulted i n increased linear bone growth and bone mineralization as well as incr eased bone maturation without remarkable adverse events. After 1 year of therapy, growth response could no longer be observed in these two p atients.