Growth hormone therapy does not alter the insulin-like growth factor-I/insulin-like growth factor binding protein-3 molar ratio in growth hormone-deficient children.
BACKGROUND
Recent studies have linked raised levels of IGF-I and/or reduced levels of its main binding protein, IGF binding protein (IGFBP)-3, with the risk of developing cancer. A GH dose-dependent increase in IGF-I/IGFBP-3 molar ratio has been reported in subjects treated with GH, raising concern about the long-term safety.


OBJECTIVE
The aim of this study was to evaluate changes in serum IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio over the first 12 months of replacement GH therapy in GH deficient (GHD) children.


METHODS
The study included 20 GHD children who had not previously received GH treatment, and 40 untreated non-GHD short children closely matched for age, gender, pubertal stage, and body mass index (BMI), as controls. Serum IGF-I, IGFBP-3 levels were measured before and after 12 months of GH treatment. Based on the molecular weight of IGF-I (7500) and IGFBP- 3 (40,000, mean of glycosylated variants), we calculated the molar ratio of IGF-I/IGFBP-3.


RESULTS
IGF-I/IGFBP-3 molar ratio significantly increased during GH therapy (p=0.01). No significant difference in IGF-I/IGFBP-3 ratio was found between GHD children and controls at the different time points. In the multiple regression analysis, BMI (beta=0.33) and age (beta=0.33) proved to be the major predictors of the IGF-I/IGFBP-3 molar ratio (adjusted r2=0.53, p<0.0001).


CONCLUSIONS
Our results suggest that at a conventional replacement dose GH does not alter the IGF-I/IGFBP-3 molar ratio. Potential fears related to long-term cancer risk are likely to be greatest in patients exposed to high-dose GH therapy and with genetic predisposition to high IGF-I and/or low IGFBP-3 concentrations.
Scirè
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Rina Balducci Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Tor Vergata University, IT-00133, Rome, Italy.
Del Bianco
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Spadoni
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Cianfarani
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D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I