ESPE Yearbook of Paediatric Endocrinology

Pediatr Res. 2025 Mar 24. Online ahead of print.PMID: 40128591 doi: 10.1038/s41390-025-04003-2

Brief Summary: This study investigated the distinct influences of height and growth hormone (GH) on brain structure-function coupling (SC-FC) in children with short stature. It specifically compared three groups: children with growth hormone deficiency (GHD), children with idiopathic short stature (ISS), and healthy controls (HC).

Substantial evidence indicates that brain gray and white matter volumes peak during childhood through early adolescence, which is crucial for cognitive development. While factors like age and sex are known to influence SC-FC coupling, the role of height remained unclear. Previous research identified brain alterations in children with short stature, but a simultaneous analysis across GHD, ISS, and HC groups to differentiate the effects of height and GH was lacking.

The authors hypothesized that both short stature and GHD would lead to distinct patterns of change in brain SC-FC coupling. They analysed retrospective data collected from children aged 6–12 years, including 71 GHD cases, 80 ISS cases, and 30 HC subjects. Clinical, behavioral assessments (using the Wechsler Intelligence Scales for Children - WISC-IV), and multimodal brain MRI data (Diffusion Tensor Imaging - DTI and resting-state functional MRI - rs-fMRI) were incorporated.

SC-FC coupling matrices were derived from DTI and rs-fMRI data.

Both short-statured groups (GHD and ISS) displayed lower scores across all behavioral cognition scales (e.g., Full-Scale IQ, Perceptual Reasoning Index, Working Memory Index) compared to HC, with no differences between GHD and ISS. This suggests the impact of height, rather than solely GH, on these outcomes. Both GHD and ISS groups exhibited reduced SC-FC coupling in primary sensory regions, specifically the Visual Network (VIS) and Sensorimotor Network (SMN), compared to HC. No differences were found between the GHD and ISS groups in these areas.

GH’s Distinct Influence in GHD: A negative correlation between peak GH levels and SC-FC coupling was observed exclusively in the GHD group. While no direct correlation between height and SC-FC coupling was found in an aggregated analysis across all three groups, the differences observed between HC and the short stature groups (GHD and ISS) still underscore the potential influence of height on brain network coupling.

The study demonstrates that height and GH levels have distinct impacts on brain SC-FC coupling in children with short stature and underscores the importance of early intervention for children with GHD, as reduced SC-FC coupling in primary sensory regions may correlate with cognitive and behavioral outcomes. The study acknowledged limitations, including its retrospective design, constrained sample size (especially for HC), and lack of extensive psychological evaluations. Future longitudinal studies are planned to investigate the effects of age and GH treatment more comprehensively.