Abstract
Pediatric Cushing disease (CD) often presents with short stature, but we have observed
significant inter-individual variability in the growth delay caused by endogenous
hypercortisolism. Glucocorticoids cause growth retardation by affecting the growth
hormone (GH) – insulin-like growth factor-1 (IGF 1) somatotropic axis, but also other,
GH-independent sites. Recently, the GH receptor (GHR) gene was found to have a common
polymorphism (P) that leads to a deletion (d3) or retention of exon 3. In this study,
we tested the hypothesis that the GH receptor polymorphism (GHR-P) maybe one of the
significant variants that determines the degree of growth delay among patients with
CD. GHR genotyping was performed on 56 children with newly diagnosed CD (24 females,
32 males, mean age of 12.9±3.3 years) who were followed at our institution between
the years 1997–2007. Correlation analysis included genotype, measures of growth and
the somatotropic axis, and anthropometrics. Within the group, 31 (12 girls, 19 boys)
expressed the full length GHR allele, 10 (4 girls, 6 boys) were d3-GHR homozygotes
and 15 (7 girls, 8 boys) were d3-GHR heterozygotes. No significant differences were
found between the GHR genotypes and patient's height and/or growth velocity, or any
other measures that we evaluated. The presence of a well-studied and common GHR polymorphism
does not appear to be responsible for the variability of growth delay observed in
patients with Cushing disease.
Key words
Cushing syndrome - cortisol - pituitary gland - growth hormone receptor - genetics
References
Correspondence
stratakc@mail.nih.gov
