Interpreting IGF-1 in children treated with recombinant growth hormone: challenges during early puberty

It can be challenging to determine the correct dosage of recombinant growth hormone (GH) in children with GH deficiency, leading to highly variable treatment responses. Insulin-like growth factor-1 (IGF-1) is a tool for monitoring GH treatment and dosing. However, IGF-1 levels depend on sex, age, and pubertal stage, amongst other factors, making its interpretation somewhat difficult. This study aimed to evaluate descriptively a group of 93 children treated per protocol with GH to assess the influence of pubertal signs and sex steroid levels on the interpretation of IGF-1.

93 (67 boys and 26 girls) prepubertal children who participated in a previous GH treatment trial were included. Age, pubertal stage, weight, height, GH dose, and IGF-1 plasma concentrations were collected at least yearly from 2 years before pubertal start and 3 years after pubertal start. Levels of estradiol in girls and testosterone in boys were analyzed from previously collected frozen samples.

Nine of 58 (15.5%) estradiol samples in girls with Tanner breast stage 1 had pubertal levels of estradiol ≥25 pmol/L. For boys with testes size <4 mL, 24 out of the 153 (15.7%) testosterone samples were above the pubertal cut-off, ≥0.47 nmol/L. All the IGF-1 samples were divided into two groups based on an IGF-1 standard deviation score (SDS) of ≥2 or <2 SDS. The IGF-1 ≥2 SDS samples had a higher median (range) GH dose, 0.042 (0.02-0.10) mg/kg/day, compared with the IGF-1 <2 SDS samples, 0.038 (0.01-0.10) mg/kg/day, p<0.001. In the IGF-1 ≥2 SDS samples vs the IGF <2 SDS samples, estradiol levels were lower among girls, 13 (3-214) vs 102 (1-1070) pmol/L p<0.001, and testosterone levels were lower among boys, 0.35 (0.11-27.2) vs 6.9 (0.04-31.2) nmol/L p<0.001.

Interpretation of IGF-1 near puberty is challenging due to the influence of sex steroids. Variations in sex steroid levels and pubertal status can lead to misleading interpretations and an overestimation of IGF-1 SDS. Establishing an IGF-1 reference range that includes sex steroid levels can improve its clinical use to monitor GH treatment.