In order to assess the relationship between insulin-like growth factor-1 (IGF-1) and the growth hormone (GH) dose utilized to treat GH-deficient children, the IGF-1 response was compared with the changes noticed in height-standard deviation scores (H-SDS) and height velocity during treatment.

The study was carried out in 24 prepubertal GH-deficient patients with a mean age of 10.5 ± 1.8 years and a mean bone age of 8.4 ± 2.1 years.  H-SDS for chronological age and bone age before therapy were -2.6 ± 0.8 and -1.2 ± 0.8, whereas height velocity was -1.1 ± 1.5 cm.  Serum IGF-1 and insulin-like-growth factor binding protein-3 (IGFBP-3) levels were measured before, after 6 months and 12 months of GH treatment, and correlated with the GH dose.   IGF-1 increased significantly during the first six months of therapy, but did not increase any further at twelve months, despite the use of higher GH dosages (0.14 vs. 0.1 IU/kg/day), whereas IGFBP-3 increased at both 6 and 12 months.  There was no correlation between GH dose and IGF-1 and IGFBP-3 levels. Height velocity as well as height for chronological age and bone age were significantly greater after one year of treatment with GH.  The authors concluded that the increment in IGF-1 during therapy did not correlate with the interval height increase and was found to be less useful than height increments in adjusting the GH dose needed to treat prepubertal GH-deficient children.

Lanes R, Jakubowicz S. J Pediatr 2002;141:606-610.

Editor’s Comment: The monitoring approach that individualizes therapy and includes both biochemical and auxological determinations to titrate the GH dose utilized to treat GH deficiency is considered standard practice in treatment with GH. A common practice is to monitor height increments and serum IGF-1 and IGFBP-3 concentrations to guide with the treatment of GH-deficient patients.  However, in this study IGF-1 and IGFBP-3 levels were not found useful in assessing the response to GH treatment.  There are wide variations in IGF-1 levels during the day, as well as different stages throughout time, and even in the same individual. Of great importance is the nutritional status and intake of the patients in relation to the IGF levels. Any one or several of these factors might have played a role in the lack of a clinically relevant, as well as statistically significant, difference in IGF levels found in this small group of patients studied.  The reader is advised to read the editorial on this paper published in the same journal by Dr. Barry Bercu¹ entitled “Titration of growth hormone dose using insulin-like growth factor-1 measurements:  Is it feasible in children?” This study once again demonstrates that careful measurements of height and the monitoring of growth progression is the most important marker in the assessment of short children with or without GH deficiency, as well as during treatment with GH. 

Reference

1.       Bercu B. J Pediatr 2002;141:601-5.

Fima Lifshitz, MD