ESPE Abstracts (2016) 86 P-P1-614

Serum [alpha]-Klotho Levels are not Informative for the Evaluation of GH Secretion in Short Children

Heba Elsedfya, Cristina Meazzab, Giorgio Radettic, Randa I. Khalafa, Sara Paganib, Nicodemo Sessad, Riccardo Albertinid, Anna Maria De Stefanoe, Antonella Navarrae, Fiorenzo Lupif, Mohamed El Kholya & Mauro Bozzolab

aPaediatrics Department, Ain Shams University, Cairo, Egypt; bPaediatric and Adolescent Unit, Internal Medicine and Therapeutics Department, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; cMarienklinik, Bolzano, Italy; dLaboratory of Clinical Chemistry Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; eIRCCS Fondazione Salvatore Maugeri, Pavia, Italy; fOspedale Regionale di Bolzano, Bolzano, Italy

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.