6825 α-Klotho Levels in Girls with Central Precocious Puberty

Abstract Disclosure: I. Hwang: None. E. Kim: None. Background: The exact mechanisms that trigger the onset of puberty are not fully understood. While it is known that elevated estradiol during puberty induces an increase in IGF-1, which subsequently promotes a rise in α-klotho levels, the relevance of these elevated α-klotho levels in children with Central Precocious Puberty (CPP) remains to be established. Given the potential significance of α-klotho in pubertal development, we initiated this study to determine whether increased α-klotho levels in CPP children are meaningfully pronounced and if these levels could serve as a reliable marker for CPP diagnosis and monitoring. Methods: A total of 139 girls were enrolled in the study, comprised of 82 diagnosed with CPP and 57 who were healthy prepubertal controls. From March 2020 to May 2023, we assessed both α-klotho levels and clinical parameters. α-klotho concentrations were measured using an α-klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment. Result: α-Klotho levels were higher in the CPP group compared with the controls (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P < 0.001). α-Klotho significantly decreased after 6 months on GnRH agonist treatment.(2147± 789 pg/mL) (P < 0.001). α-Klotho levels were positively correlated with height-SDS, weight-SDS, bone age, ALP, IGF-1 SDS, baseline FSH and LH. α-Klotho relationship with IGF-1 SDS, baseline LH studied by partial correlation with adjustment for age, height and weight SDS (r= 0.275, p= 0.003; r= -0.229, p= 0.014). A ROC curve analysis identified an α-klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing CPP girls from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723. Conclusion: Our study indicates a notable association between elevated α-klotho levels and CPP, especially as these levels adjust following GnRH agonist treatment. Based on our findings, considering α-klotho concentrations might offer a way to distinguish CPP from controls. Further studies could elucidate the potential of α-klotho as a biomarker for CPP diagnosis and monitoring. Presentation: 6/1/2024