| Objective: Central precocious puberty(CPP)is caused by early activation of the hypothalamic-pituitary-gonadal axis and is manifested by rapid development of internal and external reproductive organs and the appearance of secondary sexual characteristics.Timely diagnosis and comprehensive evaluation are keys to the successful and effective management of this disease.Gonadotropin-releasing hormone stimulation test is the critical standard for the diagnosis of CPP,while it still owns some disadvantages,such as inconvenient operation,invasive and high cost.Therefore,searching for alternative,simple and easy to operate diagnostic method has become a research hotspot.A number of recent clinical studies have shown that luteinizing hormone(LH)is an excellent predictor of CPP,but there are no uniform criteria for diagnostic thresholds.In clinical work,treatment options for patients with different central gonadal axis initiation states vary widely.Inhibin B(INHB)and Anti-Mullerian hormone(AMH)are the glycoprotein produced by ovarian granulosa cells,which have been suggested as the possible biomarkers of CPP.Previous researches show that with the onset of puberty,the concentration of INHB of girls increases while AMH levels decreases.For girls with CPP,the level of INHB is consistent with the clinical stage of maturity,suggesting that INHB could be treated as a useful tool for the clinical diagnosis of gonadal development disorders.This study will further clarify the predictive power of LH for premature thelarche(PT)and complete CPP.Serum INHB and AMH levels are also measured in girls from August 2021 to August 2022 in the above population,and ROC curve is used to analyze the predictive ability of LH,INHB and AMH alone and combined to complete CPP.Methods: The study participants are the girls who have secondary sexual characteristics before the age of 8 and were hospitalized in the Affiliated Hospital of Jining Medical University from February 2015 to August 2022.The general clinical data of these girls were collected and gonadotropin-releasing hormone stimulation tests were conducted.Based on the results of excitation,these participants were categorized into three kinds: PT,partial CPP and complete CPP.The logistic regression was used to clarify the independent correlation factors of PT and complete CPP.Receiver operating characteristic curve(ROC)was applied to analyze the predictive capability of the independent correlated factors for PT and complete CPP.Serum INHB and AMH levels were also measured in girls from August 2021 to August 2022 in the above population,and ROC curves were used to analyze the predictive ability of basal LH,INHB,and AMH,alone and in combination,for complete CPP.Results: 1.The total number of participant girls is 343,among which 114,118 and 111 girls are categorized as complete CPP,partial CPP and PT,with the average age of 8.33 ± 0.73,8.12 ± 0.74 and 7.47±1.07,respectively.There exist significant differences in basal LH among PT,partial CPP and complete CPP groups,with a median of 0.06U/L,0.30U/L and 1.50U/L,respectively.Logistic regression shows lower age(OR = 0.457;95% CI 0.305～0.686),LH(OR = 0.350;95% CI 0.144～0.852),estradiol(E2)(OR = 0.967;95% CI 0.943～0.992)and uterine volume(OR = 0.666;95% CI 0.522～0.851)are protective factors for PT;higher LH(OR = 2.146;95% CI 1.437～3.203),E2(OR = 1.034;95%CI 1.012～1.057)and uterine volume(OR = 1.500;95% CI 1.218～1.848)are independent risk factors for complete CPP.Among the above factors,LH is the best predictor for identifying PT and complete CPP with AUCs of 0.874 and 0.878,respectively.The optimal cut-points for predicting PT and complete CPP are 0.185 U/L(sensitivity 83.9%,specificity 75.9%)and 0.435 U/L(sensitivity 80.5%,specificity 84.1%),respectively.2.A total of 57 girls were tested for INHB and AMH.Compared with the PT and partial CPP groups,the complete CPP group has significantly higher INHB levels and significantly lower serum AMH levels;there is no statistically significant difference between the PT group and the partial CPP group for both AMH and INHB.ROC curve analysis shows that both AMH and INHB have good predictive ability for complete CPP with AUCs of 0.751 and 0.748,respectively.Basal LH combined with AMH and INHB has a higher AUC of 0.854 for predicting complete CPP than basal LH alone(AUC=0.795),however,due to sample size limitations,the combined model and LH alone do not reach a statistically significant difference for complete CPP does not reach a statistically significant difference in predictive power(Z=0.409,P=0.683).Conclusion: Basic LH has a good predictive capability for the developmental status of central gonads of girls,and can be treated as an early screening index for CPP.Serum INHB and AMH have a good predictive capability for the developmental status of central gonads of girls,and the combination of basal LH with these two indexes can improve the diagnostic efficacy of complete CPP. |
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