ESPE Abstracts

Background: Short stature, increased adiposity and insulin resistance are conditions frequently observed in patients with Turner syndrome (TS). Many hormones are involved in the pathogenesis of the condition but therapeutic options we can offer to the patients are still scant. Each newly discovered peptide give us hope. Klotho play a very important role in the regulation of the human body metabolism and was not investigated in patients with TS so far.

Objective and Hypotheses: The objective of the study was to investigate the concentration of Klotho protein and the response to the treatment with rHGH in patients with TS.

The study group consisted of 28 patients with TS diagnosed in one pediatric tertiary center. Their mean age was 7.6 years (range 3.2–16.1 years). The patients were diagnosed by karyotyping. Conventional G-banding and fluorescence in situ hybridization on peripheral blood cultures confirmed numerical or structural abnormalities of X chromosome or mosaicism. X chromosome monosomy was established in 14 patients (50%). Because of short stature the patients were treated with rHGH given subcutaneously once a day at bedtime, in a dose 0.05 mg/kg/day. The dose of rHGH was adjusted to body weight every 3 months. The mean period of treatment was 1.4 yr (range 0.4-3.6 yr). No other medication including estrogen replacement therapy was conducted during the study. Patients with coexisting endocrine diseases were excluded. Prior to and following the rHGH treatment anthropometric data were recorded as well as biochemical parameters were measured: Klotho, OGTT, insulin, lipids, IGF-1, and IGFBP-3.

Results: The treatment with rHGH caused a significant rise in Klotho level (1386,3 ± 663,9 vs 3421,5 ± 1320,0, mean ± SD, P = 0,000). The increase of IGF-1 SDS at the end of observation was also significant (-1.68 ± 0.49 vs 0.36 ± 1.42, mean ± SD, P = 0,000). The rHGH treatment influenced insulin resistance revealed by increased HOMA values (0.82 ± 0.56 vs 1.46 ± 1,6 P = 0.02). The correlation between Klotho and IGF-1 SDS levels was not significant neither before nor on the treatment . Klotho correlated with IGFBP3 level before rHGH treatment but not on rGH therapy. Klotho also correlated negatively with HDL cholesterol (r=-0,6) and positively with triglycerides (r=0,4) before rHGH applying.

Conclusions: Result of the study showed an increase in Klotho level following rHGH application. This effect is not mediated by IGF-1. Klotho can be used as a marker of the response to the treatment with rHGH