ESPE Yearbook of Paediatric Endocrinology

Endocrine (2024) 86:1110–1120 PMID: 39143422. doi: 10.1007/s12020-024-03992-0

Brief Summary: This observational retrospective study investigated the relationship between insulin-like growth factor-1 (IGF1) levels and body composition in 135 children (64 with Growth Hormone Deficiency (GHD) and 71 with Idiopathic Short Stature (ISS)) undergoing recombinant human growth hormone (rhGH) therapy. 305 bioimpedance analysis (BIA) was used to assess fat percentage (FATP), appendicular skeletal muscle mass (ASMM) z-score, and muscle-to-fat ratio (MFR) z-score.

The main findings regarding the relationship between IGF1 levels and body composition in pediatric patients receiving recombinant human growth hormone (rhGH) treatment are summarized as follows:

• Differences in Body Composition at Baseline: Children with Growth Hormone Deficiency (GHD) showed greater adiposity compared to those with Idiopathic Short Stature (ISS). This was evidenced by higher body mass index (BMI) z-scores, higher fat percentage (FATP), higher truncal FATP, and a lower muscle-to-fat ratio (MFR) z-score in the GHD group. Additionally, the GHD group had higher diastolic blood pressure percentiles. Importantly, the muscle component (appendicular skeletal muscle mass or ASMM z-score) did not differ between the GHD and ISS groups at this initial stage.

• Impact of rhGH Treatment on Body Composition: rhGH treatment appeared to mitigate the initial differences in adiposity between GHD and ISS patients. In rhGH-treated patients, the differences in FATP and truncal FATP between the GHD and ISS groups were no longer significant. Furthermore, rhGH-treated patients in both groups showed lower truncal FATP and higher ASMM z-scores compared to their non-treated counterparts. This suggests that rhGH treatment, by restoring normal IGF1 levels, may promote muscle growth and alleviate the detrimental metabolic impact of increased adiposity.

• Key Factors Influencing Body Composition: higher FATP (adiposity) was associated with female sex and GHD diagnosis.Higher ASMM z-score (muscle mass) was strongly linked to female sex, older age, and higher insulin-like growth factor 1 (IGF1) z-scores. Interestingly, IGF1 z-scores were found to be related to muscle mass but were not associated with adiposity (FATP) or the muscle-to-fat ratio. Neither the socioeconomic position (SEP) index nor the cumulative rhGH dose were significant contributors to any of the body composition parameters in the models. This implies that individual responsiveness to rhGH, mediated by endogenous IGF1 secretion, is a more influential factor for muscle mass than the total dose administered.

• Role of IGF1 Levels: The findings highlight that sex- and age-adjusted IGF1 levels are crucial for determining muscle mass. IGF1 plays a critical role in regulating protein metabolism by enhancing amino acid transport into muscle cells and inhibiting protein degradation, thereby contributing to skeletal muscle preservation and expansion.

• Sex Dimorphism: Female sex was a contributing factor for increased adiposity (higher FATP). However, surprisingly, female sex was also a contributor to a favorable sex- and age-adjusted muscle mass (ASMM z-score) and a better muscle-to-fat ratio z-score. Females also demonstrated a greater increase in IGF1 z-score over time after adjusting for cumulative rhGH dose.

In conclusion, children with GHD are at a higher risk of increased adiposity. The study suggests that rhGH treatment, by restoring normal IGF-1 levels and thereby promoting muscle growth, may help mitigate the adverse metabolic effects associated with this increased adiposity. This highlights the importance of considering both fat and muscle components when managing pediatric patients with GHD. The main strength of the study is its standardized and comprehensive assessment, while a limitation is its cross-sectional design, which precludes causal inferences.

References: 1. Grimberg, D.B. Allen, Growth hormone treatment for growth hormone deficiency and idiopathic short stature: new guidelines shaped by the presence and absence of evidence. Curr. Opin. Pediatr. 29, 466–471 (2017).2. Duan, H. Ren, S. Gao, Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins: Roles in skeletal muscle growth.3. T.V. Bersin et al. Nutritional status affects Igf1 regulation of skeletal muscle myogenesis, myostatin, and myofibrillar protein degradation pathways in gopher rockfish (Sebastes carnatus). Mol. Cell. Endocrinol. 573, 111951 (2023).