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Horm Metab Res 2010; 42(3): 194-197
DOI: 10.1055/s-0029-1242744
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

The Growth Hormone Receptor (GHR) Polymorphism in Growth-retarded Children with Cushing Disease: Lack of Association with Growth and Measures of the Somatotropic Axis

L. Drori-Herishanu1 , M. Lodish1 , 2 , S. Verma1 , 2 , E. Bimpaki1 , M. F. Keil2 , A. Horvath1 , C. A. Stratakis1 , 2
  • 1Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN), National Institutes of Health (NIH), Bethesda, USA
  • 2Pediatric Endocrinology Inter-Institute Training Program (PEITP), National Institutes of Health (NIH), Bethesda, USA
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Publikationsverlauf

received 02.05.2009

accepted 18.10.2009

Publikationsdatum:
09. Dezember 2009 (online)

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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

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Correspondence

C. A. StratakisMD, D(Med).Sc. 

Chief, Section on Endocrinology & Genetics (SEGEN)

Director Pediatric Endocrinology

Training Program DEB NICHD NIH

Building 10

CRC, Room 1-3330

10 Center Dr., MSC1103 Bethesda

20892 Maryland

USA

Telefon: +1 301 496 4686/496 6683

Fax: +1 301 402 0574/480 0378

eMail: stratakc@mail.nih.gov