Urinary metabolomic biomarkers for diagnosing central precocious puberty and revealing sexual dimorphism

The incidence of central precocious puberty (CPP) is rising, especially during the COVID-19 pandemic. Early detection is crucial to prevent adverse outcomes in affected children. Current diagnostic methods are invasive and inconsistent, necessitating less invasive approach. Metabolomics offers a novel method to reveal CPP mechanisms and identify biomarkers.

This study aims to identify and validate urinary metabolomic biomarkers for the diagnosis of CPP and to elucidate the sex-dimorphic metabolic mechanisms underlying this condition, with the ultimate goal of developing non-invasive diagnostic approaches.

Urine samples from CPP patients and aged-matched controls were analyzed using NMR-based metabolomics. Statistical analyses identified potential CPP biomarkers. LASSO regression and binary logistic regression (LR) screened diagnostic groups, validated using random forest, LR and support vector machine to generate receiver operating characteristic (ROC) curves and calculate area under curves (AUCs). Direct comparison between CPP boys and girls discerned gender-specific metabolic characteristics.

The study identified 13, 13, 17 and 12 potential markers for CPP girls versus prepubertal/adolescent girls, and CPP boys versus prepubertal/adolescent boys, respectively. Diagnostic groups with 7, 3, 3 and 3 biomarkers were selected, yielding mean AUCs of 0.928, 0.942, 0.984 and 0.865. Eight gender-specific markers were identified.

The study reveals distinct metabolic differences between CPP children and controls, with gender variations. Obesity is a risk factors for CPP in girls, while CPP boys exhibit faster amino acid turnover and bone growth. Gender comparison shows distinct metabolic profiles, confirming sexual dimorphism in CPP presentation. These findings suggest that metabolic regulation interventions may be beneficial in managing CPP and highlight the need for gender-specific diagnostic approaches.