ESPE Yearbook of Paediatric Endocrinology

Horm Res Paediatr. 2024 Nov 21:1-12. PMID: 39571543. doi: 10.1159/000542579

Brief Summary: This study investigated clinical predictors of response to growth hormone treatment (GHT) during the first year in children with Idiopathic Short Stature (ISS). ISS is a heterogeneous condition in which a child is significantly shorter than peers of the same age and sex, without identifiable systemic, endocrine, nutritional, or chromosomal causes, and with normal endogenous GH secretion. While GHT can help some ISS patients to achieve normal adult height, its use remains debated due to variable treatment responses.

The analysis included data from two large observational registries: NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905). The study population comprised 207 prepubertal children aged 3–11 years (boys) and 3–10 years (girls) at treatment initiation. Patients were classified based on their first-year change in height standard deviation score (ΔHSDS): good responders (ΔHSDS > 1.0), middle responders (ΔHSDS 0.4–1.0), and poor responders (ΔHSDS < 0.4). Responsiveness to GH dose was also assessed by annualized ΔHSDS per 10 μg/kg/day GH, categorizing patients into high, medium, and low responsiveness groups.

Younger age at treatment initiation was associated with a higher likelihood of good response (Odds Ratio [OR] 0.69, 95% CI 0.5–0.9; p = 0.0169). Good responders had the lowest mean age (6.4 years). Greater distance from target HSDS predicted better response (OR 2.05, 95% CI 1.1–3.9; p = 0.0259). Good responders had the largest mean distance from target HSDS (2.3).In univariate analysis, target HSDS (OR 2.66; p = 0.016) and maternal HSDS (OR 1.78; p = 0.058) were also notable predictors. Neither sex nor average GH dose in the first year independently predicted response in multivariate models. When stratified by responsiveness to GH dose, a positive correlation between GH dose and ΔHSDS was found in the high and medium responsiveness groups (p = 0.003 and p < 0.001, respectively). Female sex (OR 0.24; p = 0.042) was associated with low responsiveness to GH dose, whereas greater distance from target HSDS predicted high responsiveness (OR 1.85; p = 0.045).

In conclusion, younger age at treatment start and a greater distance from target HSDS are clinical predictors of better first-year response to GHT in children with ISS. The heterogeneity in GH dose responsiveness suggests underlying individual and possibly genetic differences. Further research into genetic factors may help personalize treatment and improve outcomes.

References: 1. Hintz RL. Growth hormone treatment of idiopathic short stature. Horm Res. 1996; 46(4–5):208–14.2. Bakker B, Frane J, Anhalt H, Lippe B, Rosenfeld RG. Height velocity targets from the National Cooperative Growth Study for firstyear growth hormone responses in short children. J Clin Endocrinol Metab. 2008; 93(2):352–7.3. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the growth hormone research society, the lawsonwilkinspediatric endocrine society,and the European society for paediatric en- docrinology workshop. J Clin Endocrinol Metab. 2008;93(11):4210–7.4. Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review. BMJ. 2011;342:c7157.