ESPE Abstracts

Background: Klotho is an anti-aging protein acting as a circulating hormone. Major physiologic activities attributed to klotho include regulation of phosphate and calcium homeostasis, aging, adipogenesis, and glucose metabolism. Pubertal children had higher klotho than prepubertal. Insulin like growth factor-1 (IGF-1) directly promotes klotho shedding. Klotho levels significantly correlated with IGF-1 standard deviation scores (SDS).

Objects: Elevated klotho levels during puberty may be associated with elevated IGF-1 concentrations, which may also be observed in central precocious puberty (CPP). We investigated the effect of GnRH agonist treatment on klotho levels in children with CPP and factors related with change of klotho levels.

Methods: Klotho levels were measured in 82 CPP girls aged 8.42 ± 0.65 years treated with GnRH agonist between March 2020 and May 2021. All subjects had samples obtained between before and 6 months after the treatment. Klotho levels were measured using an 𝛼-klotho ELISA kit. A compared t-test was used to compare continuous variables between before and 6 months after the onset of GnRH agonist treatment groups. Pearson’s correlation analysis was examined to determine the relationship between 𝛼-klotho and other clinical variables. Subjects after 6 months of GnRH agonists treatment were considered prepubertal girls, and receiver operating characteristic curve used to discriminate the ability of 𝛼-klotho to detect CPP.

Results: After GnRH agonists treatment, peak LH, peak FSH, estradiol, alkaline phosphatase, and IGF-1 SDS were statistically significantly decreased in all subjects (P<0.001). 𝛼-klotho levels decreased from 2529.36 ± 999.51 pg/ml to 2147.50 ± 789.62 pg/ml (P<0.001) after 6 months of treatment with GnRH agonists. After adjusting for age and BMI SDS, 𝛼-klotho levels showed positive correlations with peak LH (r=0.274, p=0.014) before treatment, but no correlation after treatment. 𝛼-klotho showed a weak correlation with IGF-1 SDS when analyzed including all subjects before and after treatment after adjusting for age and BMI SDS (r=0.157, p=0.05). The area under the curve for 𝛼-klotho was 0.686 (95% confidence interval: 0.594–0.777, p=0.012) with 59.4% of sensitivity and 73.4% of specificity.

Conclusions: The results of this study suggest the role of 𝛼-klotho as a possible marker to detect CPP. Further studies to compare klotho levels between patient with CPP and prepubertal children and to establish cut-off levels for CPP are needed in the future.