Recommended IGF-I Dosage Causes Greater Fat Accumulation and Osseous Maturation Than Lower Dosage and May Compromise Long-term Growth Effects

Abstract

Abstract Context: The maximum dose of IGF-I recommended for treatment of GH insensitivity is commonly used. Objective: The aim was to test the hypothesis that a lower dose is as effective as a high dose of IGF-I in growth promotion and has fewer deleterious effects. Design and Setting: Subjects were treated for 3 years with regular examinations including bone age and dual energy x-ray absorptiometry and for 1 year with abdominal ultrasound studies at a clinical research institute in Quito, Ecuador. Subjects: The study included 21 subjects ages 3.2–15.9 years with GH insensitivity due to the same splice site mutation on the GH receptor gene. Interventions: Subjects were allocated to receive 120 (n = 14) or 80 (n = 7) μg/kg IGF-I twice daily. Main Outcome Measures: Height velocity, osseous maturation, height SD scores (SDS), body composition, abdominal organ growth, and side effects were assessed. Results: There were no differences in growth velocity or height SDS increment by dosage, and the SDS increase was greater than in other reported series. Osseous maturation over 3 years with the high dose was nearly twice as rapid as with the lower dose (P < .001) and correlated with an increase in percentage body fat (r = .64; P < .001) and with adrenal size increase over 1 year (r = .32; P = .03). The ratio of bone age to height age was lower in the high-dose group after 3 years of treatment (P = .007). Conclusions: The commonly used IGF-I dosage of 120 μg/kg twice a day is excessive in comparison to a dose of 80 μg/kg twice a day, disproportionately accelerating osseous maturation, probably from the combined effects of obesity and inappropriate adrenal growth, thus likely compromising adult height potential. Moreover, the lower dose decreases direct treatment cost by one-third.