Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.

The Kp-10/basal LH ratio may help differentiate ICPP from PT in young girls, potentially reducing the need for invasive GnRH stimulation testing.

Summary and findings

This study evaluated the diagnostic performance of Kisspeptin-10 (Kp-10) in distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) in Indian girls aged 6-9 years. The Kp-10/basal LH ratio demonstrated a sensitivity of 72.7% and specificity of 87.0% with an ROC-derived cut-off of <4.07 ng/mIU. No significant anthropometric differences were found between the groups.

Abstract

Background Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are key regulators of GnRH secretion and may serve as surrogate biomarkers. We evaluated whether these neuropeptides, alone or in combination with basal gonadotropins, could provide clinically useful discrimination of ICPP and PT. Methods In this prospective study, Indian girls aged 6-9 years were enrolled as controls (n = 40), ICPP (n = 33), and PT (n = 23). Anthropometry, basal LH, FSH, estradiol, pelvic ultrasonography, and plasma Kp-10, NKB, and NPY levels were assessed. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Logistic regression models assessed incremental predictive value: Model 1 included the Kp-10/basal LH ratio; Model 2 added bone age advancement (BA-CA); and Model 3 further included basal estradiol. Clinical utility was examined using decision curve analysis (DCA). Results Anthropometric parameters did not differ between ICPP and PT. Kp-10 and NKB levels were higher in both early-puberty groups than controls, but neither marker alone discriminated ICPP from PT. The composite Kp-10/basal LH ratio showed superior performance, with an ROC-derived cut-off <4.07 ng/mIU (sensitivity 72.7%, specificity 87.0%, accuracy 78%). All three models showed similar discrimination (AUC 0.78-0.79), with no meaningful improvement after adding BA-CA or estradiol. DCA demonstrated a higher net benefit for the Kp-10/basal LH ratio compared with treat-all or treat-none strategies across clinically relevant thresholds. Conclusion The Kp-10/basal LH ratio provides robust discrimination and meaningful clinical utility in differentiating ICPP from PT and may reduce reliance on GnRH stimulation testing.

Key findings

• Not reported in abstract.

Limitations

• Not reported in abstract.

Elsewhere in the Kisspeptin (KP-10) corpus