The role of kisspeptin and MKRN3 in the diagnosis of central precocious puberty in girls

Abstract

Objective: To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty (CPP) in girls.

Method: Thirty four individuals with CPP, 17 individuals with premature thelarche (PT), and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included BMI and tests for breast, bone, and sexual characteristics. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3, and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90, and 120 min after injection with triptorelin.

Results: Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P = 0.020), while serum MKRN3 levels were lower in the two groups (P = 0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P > 0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5.

Conclusions: Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.

Keywords: central precocious puberty; gonadotropin-releasing hormone; makorin ring finger protein 3; premature thelarche.

Figure 1

Positive correlations between circulating kisspeptin levels and (A) B-LH and (B) B-FSH in patients with the CPP, PT, and NC groups. (A, r = 0.325, P = 0.004; B, r = 0.278, P = 0.013).

Figure 2

Inverse correlations between circulating MKRN3 levels and BMI in patients from the CPP, PT, and NC groups. (r = –0.247, P = 0.028).

Figure 3

The receiver operating characteristic curves of kisspeptin and MKRN3 levels. The areas under curve for identifying the patients with or without CPP were 0.707 (95% CI: 0.572–0.842, P = 0.005) and 0.699 (95% CI: 0.568–0.829, P = 0.008), respectively. The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity.