The role of serum growth hormone and insulin-like growth factor-1 in adult humans brain morphology

Abstract

Growth hormone (GH) and its anabolic mediator, insulin-like growth factor-1 (IGF-1), have a critical role in the central nervous system. However, their detailed roles in the adult human brain are not clear. In this study, structural MRIs of 48 patients with GH-secreting pituitary adenoma (GH-PA), 48 sex-and age-matched clinical Non-Functional pituitary adenoma patients (NonFun-PA) and healthy controls (HCs) were assessed using voxelbased morphometry (VBM) and region-based morphometry (RBM). Correlation analyses helped determine the relationships between serum hormone levels and brain structure. The whole-brain gray matter volume (GMV) and white matter volume (WMV) significantly increased at the expense of cerebrospinal fluid volume (CSFV) in GH-PA (Bonferroni corrected, p<0.01). The increase in GMV and reduction in CSFV were significantly correlated with serum GH/IGF-1 levels (p<0.05). VBM showed significant correlations of the GMV/WMV alteration pattern between GH-PA vs HCs and GH-PA vs NonFun-PA and widespread bilateral clusters of significantly increased GMV and WMV in GH-PA (pFDR<0.05). RBM showed obviously increased GMV/WMV in 54 of 68 brain regions (p<0.05) in GH-PA compared to HCs. Our results provide imaging evidence that serum GH/IGF-1 contributes to brain growth, which may be a potential treatment option for neurodegenerative disorders and brain injury in humans.

In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma

“…In our study, we found widespread increases in cortical thickness in the patients with acromegaly compared to the controls with SBM analysis. This result is consistent with our previous voxel-based morphometry (VBM) analysis, which showed a diffuse increase in GM volume (17). The diffuse increase in cortical thickness may be related to the role of GH/ IGF-1 in contributing to the proliferation of cells in the CNS (10,30).…”

“…In addition, we also found that Viso was significantly increased in the WM fiber bundles in acromegaly relative to controls, which indicated that increased extracellular fluid in the white matter was caused by long-term excessive hormone levels. In our previous study, we found diffuse increases in WM volume in patients with acromegaly (17). This may be due to the increase in extracellular fluid in white matter.…”

“…In our previous study, we found that higher serum GH/IGF-1 levels significantly increased the volume of brain tissue (grey matter (GM) and white matter (WM) at the expense of cerebrospinal fluid volume (CSFV) and that GH/IGF-1 levels were associated with GM volume and CSFV, but not white matter volume, in acromegalic patients (17). In the current study, 29 active acromegalic patients (growth hormone-secreting pituitary adenoma) and 31 controls (patients with non-functional pituitary adenoma) were recruited to characterize the cortical and white matter microstructural pathology in acromegalic patients.…”

Cognitive Dysfunction, an Increasingly Valued Long-Term Impairment in Acromegaly

“…Sievers et al [ 27 ] found increased gray and white matter in the cerebral hemispheres, particularly in the left and right lateral hippocampus, of patients with acromegaly, especially early in the course of the disease. This finding was confirmed by Yuan et al [ 71 ] in 2020, further finding a decrease in cerebrospinal fluid volume (CSFV) and that these changes significantly correlated with serum GH and IGF-1 levels. A subsequent in-depth study by Yuan et al [ 36 ] showed a general decrease in T1/T2 weighted ratio in most cortical and white matter in patients with acromegaly, implying extensive cortical and white matter demyelination and myelin regeneration.…”

Effectiveness of Recombinant Human Growth Hormone Therapy for Children With Phelan-McDermid Syndrome: An Open-Label, Cross-Over, Preliminary Study

“…IGF-1 is a 70amino acid polypeptide hormone primarily produced in the liver, which is well known to promote the peripheral effects of GH and serve as the mediator factor for GH's actions. IGF-1 in circulation can bypass the blood-brain barrier into the brain tissue and cerebrospinal fluid, activating its receptors as GH does (31,32). Previous studies have reported the GH-IGF-I axis plays an important role in multiple brain functions and might be targeted as a promising therapy for neurodegenerative diseases such as Amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and dementia (33)(34)(35)(36).…”