Serological biomarker models composed of luteinizing hormone, kisspeptin, vitamin D and estradiol, and their clinical test value in girls.

OBJECTIVE

Central precocious puberty (CPP) may lead to premature pubertal onset. While the GnRH stimulation test remains the gold standard, its invasive nature and prolonged procedure limit clinical utility, particularly in pediatric populations. Emerging biomarkers, including luteinizing hormone, estradiol, kisspeptin, and vitamin D, have shown promise in distinguishing CPP from normal puberty. This study systematically evaluated the diagnostic utility of these biomarkers both individually and in novel combinatorial models, with the aim of establishing a non-invasive and more accessible diagnostic alternative for CPP.

METHODS

This retrospective study included 129 girls with CPP and 116 age-matched controls. Clinical characteristics, including height, weight, body mass index, and bone age, were recorded. Serum levels of luteinizing hormone, estradiol, kisspeptin, vitamin D, progesterone, and prolactin were measured. The diagnostic performance of individual biomarkers and three combined biomarker models was assessed using receiver operating characteristic curve analysis.

RESULTS

Model 1 included luteinizing hormone and kisspeptin, Model 2 incorporated vitamin D, and Model 3 added estradiol. CPP patients exhibited significantly higher levels of luteinizing hormone (2.51 vs. 0.23 mIU/mL), kisspeptin (1.59 vs. 0.96 μg/L), and estradiol (25.86 vs. 13.41 pg/mL) and lower vitamin D levels (20.13 vs. 25.90 ng/mL) compared to controls (all p < 0.001). Model 3 demonstrated the highest diagnostic accuracy with an AUC of 0.939 (95 % CI: 0.910-0.968), sensitivity of 89.06 %, and specificity of 87.93 %, outperforming individual biomarkers and other models.

CONCLUSION

This study highlights the potential of combining luteinizing hormone, kisspeptin, vitamin D, and estradiol into a single diagnostic model for CPP.