Morphological changes and lateralization of the thalamic nuclei in children with growth hormone deficiency

Joo Young Lee^1*Sung-min Lim²Jung Hwan Oh³Yong Hun Jang¹Gang Yi Lee¹Jeong-Kyu HOH³Seung Yang³Hyun Ju Lee^3*

• ¹Hanyang University, Seoul, Republic of Korea
• ²Hanyang University Seoul Hospital, Seongdong-gu, Republic of Korea
• ³Hanyang University College of Medicine, Seongdong-gu, Republic of Korea

Introduction: Childhood growth hormone deficiency (GHD) is an endocrine disorder characterized by reduced secretion of growth hormone (GH), leading to impaired linear growth and delayed developmental milestones. Recent studies suggest that GHD is associated with cognitive, socio-emotional, and behavioral impairments, potentially via altered neurodevelopment, with neuroimaging studies revealing changes in brain morphology and broader GH-related effects on the central nervous system. The thalamus, a major subcortical relay integrating sensory, motor and cognitive information, has received limited attention in neuroimaging studies of children with GHD. This study aimed to investigate morphological alterations and characterize lateralization patterns of thalamic nuclei in children with GHD. Methods: Fifteen children diagnosed with GHD and fifteen age- and sex-matched children with idiopathic short stature (ISS) were recruited. The pituitary gland was segmented using ITK-SNAP software. Thalamic nuclei were delineated and parcellated into ten regions using Bayesian MRI methods and a probabilistic atlas. Lateralization indices were calculated as: ((Left−Right)/(Left+Right)) × 100. Group comparisons and correlation analyses were conducted with age and sex as covariates. All volumes were normalized to total intracranial volume (tICV). Results: Children with GHD exhibited a significantly smaller pituitary gland volume compared to those with ISS, even after adjustment for age, sex, and tICV. In children with GHD, the anteroventral (AV) thalamic nucleus showed increased volume, and the ventral anterior (VA) nucleus exhibited significantly greater leftward asymmetry compared to ISS. Moreover, there was a significant positive correlation between the lateralization index (LI) of the AV nucleus and serum IGF-1 levels (p=0.022) and between the LI of the VA nucleus and serum IGF-1 levels (p=0.022). Similarly, the LI of the AV nucleus was significantly positively correlated with serum IGFBP-3 levels (p=0.022), and there was also a significant correlation between the LI of the VA nucleus and serum IGFBP-3 levels (p=0.033). Conclusion: The observed leftward lateralization in the anterior thalamic nuclei, together with associations with serum IGF-1 and IGFBP-3 levels, suggests that thalamic lateralization reflects a neurodevelopmental adaptation to disrupted GH signaling. These findings suggest that GH/IGF activity shapes subcortical development in a dose-dependent manner and reveal structural adaptations in hormone-sensitive regions to early endocrine disruption.