ESPE Abstracts

Introduction: Short stature is one of the most common reasons for children presenting to an endocrinologist. In normal conditions, growth hormone (GH) stimulates the IGF-1 production in hepatocytes via the STAT5 signaling pathway. Approximately 40% of children diagnosed with idiopathic short stature (ISS), i.e. with normal GH secretion, have a reduced IGF-1 level for unknown reasons. Recently, it has been described that there are certain factors that reduce IGF-1 secretion by inhibiting STAT5. These include sirtuin 1 (SIRT1) and fibroblast growth factor 21 (FGF-21). The aim of the study was to assess the concentration of SIRT1 and FGF21 in children with ISS and to compare the results with those observed in children with GH deficiency (GHD) and healthy controls as well as to analyse the relationship between SIRT1 and FGF21 and height, GH secretion and IGF-1 and IGFBP3 concentrations in children.

Materials and methods: The study group included 102 children with short stature (height SDS below -2.0). According to maximal GH concentrations (maxGH) in two different stimulation tests, children were qualified into GH deficiency (GHD) group – maxGH <10 ng/ml (n=40) or ISS group – maxGH≥10 ng/ml (n=62). The Control group consisted of healthy children with normal height (n=48). In each child SIRT1, FGF21, IGF-1 and IGFBP3 concentrations were determined.

Results: In the total group the median age was: 10.8 (8.4-12.7) years; there was no significant difference in age and sex between GHD, ISS and Control groups. SIRT1 levels were similar in the ISS and GHD groups, but in both those groups significantly higher than in the Control group [median (25%-75%): 0.97 ng/ml (0.64- 2.0) vs 0.79 ng/ml (0.48-1.22) vs 0.36 ng/ml (0.14-0.38), P=0,000, respectively]. FGF21 levels did not differ between the groups. A significant negative correlation was found between SIRT1 and: height SDS (r= -0,44), IGF-1 (r= -0,21), and IGF-1/IGFBP3 molar ratio (r= -0,18).

Conclusions: In short stature children, regardless of GH secretion, SIRT1 concentrations are elevated. Since there are significant negative correlations between the concentration of SIRT1 and the level of IGF-1, IGF-1/IGFBP3 molar ratio and the degree of growth deficiency, it can be assumed that elevated SIRT1 levels are a mechanism that inhibits IGF-1 secretion in short stature children. FGF21 does not appear to have a significant role in inhibiting the intracellular GH signal for IGF-1 production in children with short stature.