Kisspeptin-10/basal LH ratio robustly differentiates central precocious puberty from premature thelarche

Accurately distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) is a significant clinical challenge. Current diagnostic protocols often necessitate a GnRH stimulation test, which is invasive, time-consuming, and costly. Identifying less burdensome, non-invasive biomarkers is crucial for pediatric endocrinology. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are known to regulate GnRH secretion and the hypothalamic-pituitary-gonadal (HPG) axis, making them promising candidates for improved diagnostic tools.

This prospective study enrolled 96 Indian girls aged 6-9 years, comprising 40 controls, 33 with ICPP, and 23 with PT. Researchers assessed anthropometric parameters, basal LH, FSH, and estradiol levels, and performed pelvic ultrasonography. Plasma levels of Kisspeptin-10, NKB, and NPY were measured. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Logistic regression models were constructed to assess 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). There was no therapeutic intervention or specific dose of Kisspeptin-10 administered, as it was measured as a biomarker.

Anthropometric parameters showed no significant differences between the ICPP and PT groups. Plasma Kisspeptin-10 and NKB levels were found to be higher in both early-puberty groups (ICPP and PT) compared to controls. However, neither Kisspeptin-10 nor NKB alone could effectively discriminate between ICPP and PT. The composite Kisspeptin-10/basal LH ratio demonstrated superior diagnostic performance. An ROC-derived cut-off of <4.07 ng/mIU for this ratio achieved a sensitivity of 72.7%, a specificity of 87.0%, and an overall accuracy of 78% in differentiating ICPP from PT. All three logistic regression models, including those with additional markers like bone age advancement or estradiol, showed similar discrimination with an AUC ranging from 0.78-0.79, indicating no meaningful improvement beyond the Kp-10/basal LH ratio.

Decision curve analysis (DCA) further revealed a higher net benefit for using the Kisspeptin-10/basal LH ratio compared to 'treat-all' or 'treat-none' strategies across clinically relevant diagnostic thresholds.