ESPE Abstracts

Serum levels of insulin-like growth factor-1(IGF-1) are used universally for monitoring growth hormone (GH) therapy in patients with GH deficiency (GHD). However, the serum levels of IGF-1 are variable, therefore in the last years the serum levels of IGF binding protein-3 (IGFBP-3) and the molar ratio IGF-1/IGFBP-3 were introduced as more effective and stable parameters evaluating the safety and efficacy of GH treatment. Many studies present reference values of IGF-1, IGFBP-3 and evaluation of their ratio (as SD, as logarithm, as specific formula), but currently there is no unified method to compare these parameters.

Objective: The aim of this study is to compare the serum levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio with already presented models in order to propose new reliable and easy to use in the everyday practice tool for supporting the assessment of the GH therapy efficacy and safety in GHD patients.

Design: Serum levels of IGF-1 (ng/ml) and IGFBP-3 (ng/ml) were measured in 72 GHD patients (73.6% boys, age range 1-18 years) treated with GH and followed up at a tertiary University pediatric endocrinology center. Blood samples (n = 104) were analyzed at different points of the patients’ observation (2019-2020) – before starting of therapy (n = 7), during the 1^st year of treatment (n = 26), during the 2^nd year (n = 15) and after 2 years of treatment (n = 56). IGF-1 to IGFBP-3 was calculated as a simple ratio without any prior adjustments.

Results: Before treatment, levels of IGF-1(mean 118.8±75.8ng/ml), IGFBP-3 (mean 4100±1776ng/ml) and IGF-1/IGFBP-3 ratio (mean 0.027±0.009) correlated highly with the values in SD (r = 0.69, P < 0.05) and specific formula for calculating molar ratio (r = 0.72, P = <0.05). After initiation of GH therapy increase in IGF-1 and IGFBP-3 concentrations was observed (mean 263.9±86.2ng/ml and 5850±2130ng/ml) which correlated positively with results from other studies. The IGF-1/IGFBP-3 ratio for the 1^st year also increased to 0.042±0.023, median 0.036±0.027. Increase of the IGF-1/IGFBP-3 ratios was observed until the second year of treatment, then they remained stable. The ratio did not correlate with age, sex or pubertal status, just with the GH therapy year since start.

Conclusion: The results of this study revealed that the proposed calculation of IGF-1/IGFBP-3 ratio could be used as easily accessible index during GH treatment. Its relation with other parameters of efficacy and safety as well as its behavior in other GH treated conditions remains to be further elucidated.