ESPE Abstracts

Background: Kisspeptin and Delta-like 1 homolog (DLK1) are neuropeptides that regulate pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis; consequently, measuring these biomarkers could potentially distinguish central precocious puberty (CPP) from premature thelarche (PT) girls and monitor CPP treatment.

Objectives: To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis with age-matched PT girls and after CPP treatment.

Methods: From November 2009 to July 2022, a cross-sectional study was conducted in Pediatric Endocrinology Clinic of King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. CPP and PT were defined as girls with breast onset before the age of eight years and peak LH levels of ≥ 6 IU/L and < 6 IU/L after the GnRH stimulation test, respectively. Serum Kisspeptin and DLK1 levels were measured by ELISA at baseline in both groups and 6 months after GnRH analogue treatment in the CPP group. Wilcoxon rank sum test and Chi-square test were used to compare continuous and categorial data between CPP and PT. Serum Kisspeptin and DLK1 levels in CPP were compared using the Wilcoxon sign rank test before and after treatment.

Results: Of the 48 participants included in the study, 24 are CPP girls (mean age 7.7 ± 0.7 years) and 24 are PT girls (mean age 7.4 ± 0.8 years). CPP girls were significant taller (132.6 ± 7.6 cm vs. 126.4 ± 6.7 cm, P<0.05) and had more advance bone age than PT girls [1.08 (0.08-2.03) years vs. 0.11 (-0.84-0.71) years, P<0.05]. In response to GnRH stimulation test, the CPP group had significantly higher basal LH, FSH and estradiol levels, basal LH/FSH ratio, peak LH levels, and peak LH/FSH ratio than PT group (P<0.05). Baseline serum Kisspeptin levels in CPP and PT group were 50.5 (38.2-77) and 49.5 (39.7-67.6) pg/mL, respectively (P=0.89), while baseline serum DLK1 levels were 6.5 (5.9-7.5) and 6 (4.4-14.4) ng/dL, respectively (P=0.68). After six months of treatment in CPP group, median serum kisspeptin levels were lower than baseline [46.4 (37.1-60) pg/mL, P=0.002], although median serum DLK1 levels were higher than baseline [7 (6.7-8.9) ng/mL, P=0.002].

Conclusion: Baseline serum Kisspeptin and DLK1 levels cannot be used to differentiate CPP from PT in Thai girls; however, significant changes in serum Kisspeptin and DLK1 levels are observed after CPP treatment. More studies are required to elucidate the clinical use of these biomarkers as a monitoring tool for CPP treatment.