Background: α-klotho is a transmembrane protein which can be cleaved and act as a circulating hormone. Since low α-klotho levels were found in organic GH deficiency (GHD) and high levels in acromegaly, an interaction between α-klotho, GH and linear growth has been suggested.
Objective and hypotheses: We investigated the role of α-klotho protein as a reliable marker of GH secretion in short children and the factors influencing its secretion. For this purpose, we used the pegvisomant-primed GH stimulation test, since pegvisomant acts as enhancer of GH secretion.
Method: We enrolled 20 Egyptian short children with reduced GH secretion (GH peak <10 ng/ml) after two pharmacological stimuli (clonidine and insulin tolerance test) and 20 subjects with normal GH secretion. Then, pegvisomant was injected subcutaneously and after three days a GH stimulation test (insulin tolerance test) was performed. The baseline samples obtained before and after pegvisomant were used for measuring IGF-I and α-klotho. α-klotho levels were measured by an ELISA assay, IGF-I and GH levels were determined by a chemiluminescent assay which has no cross-reaction with pegvisomant.
Results: α-klotho basal levels were not significantly different between GHD and non-GHD children. After pegvisomant priming, a reduction in IGF-I and α-klotho levels was found in both groups. Furthermore, α-klotho basal levels significantly correlated with IGF-I levels in both groups and with the area under the curve of GH secretion (GH-AUC) only in non-GHD subjects. In these children, the reduction of α-klotho depends on the basal α-klotho and IGF-I levels and on the reduction of IGF-I but not on GH-AUC. On the contrary, in GHD children, the correlation with basal α-klotho levels was no longer significant after adjusting for BMI.
Conclusion: In conclusion, IGF-I and the nutritional status have a role in the regulation of circulating α-klotho. Therefore, α-klotho is not a reliable biomarker for GH secretion in children.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology