Endocrine Abstracts (2011) 27 OC2.5

A selective effect of IGFBP3 on brain volumes in healthy children

Emma Webb, Jon Clayden, C J Edmonds, K Seunarine, A Singhal, J Lanigan, A Lucas, C Clark, E Isaacs & M T Dattani

Institute of Child Health, London, UK.

Background: GH deficiency is associated with reduction in IQ and neural volumes (globus pallidum and thalamus). Significant relationships between IGF1, IGFBP3 and brain volumes have also been described in children born extremely preterm (total brain volume and cerebellum). No published studies report the relationship between markers of GH status and brain volumes in healthy children.

Methods: Cognitive assessment, MRI brain and measurement of IGF1 and IGFBP3 were performed. Neural volumes were determined. Partial correlation was performed to assess the relationship between IGF1 and IGFBP3 SDS; IQ (controlled for socioeconomic status) and MRI measures (controlled for age, sex and total brain volume). P values for significance were adjusted to control for the false discovery rate.

Results: Two hundred and seventy-nine individuals were recruited; 254 children (150 males) underwent both cognitive testing, and measurement of serum IGF1 and IGFBP3 (mean 11.7 years). Of these 254, 161 (99 males) underwent unsedated MRI; volumetric data were available for 95. Neither IGF1 or IGFBP3 SDS correlated with IQ. IGF1 SDS did not correlate significantly with neural volumes. IGFBP3 SDS correlated significantly with right cerebellum (P<0.02), globus pallidum (left P<0.01, right P<0.007) and thalamic (left P<0.02, right P<0.004) volumes.

Conclusion: We have identified significant correlations between IGFBP3 and pallidum, thalamus and cerebellar volumes in healthy children. Similar relationships have previously been identified in extreme preterm and GH deficient children. This suggests that the association between neural volumes and IGFBP3 is real and that circulating concentrations of IGFBP3 significantly influence brain development. Interestingly, in individuals with GHD we also found a significant relationship between IGF1 and IGFBP3 SDS and IQ. The lack of association between cognitive function and the IGF1 axis in the current cohort suggests that children with a normal GH axis may be less vulnerable to variations in the IGF1 axis than individuals with GH abnormalities.

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