Gul Siraz Ulku, Karadag Ayse, Ozsoy Nazlı Sultan, Kaygi Tartici Emine, Aliyeva Aynura, Kurtoglu Selim, Hatipoglu Nihal
Department of Pediatric Endocrinology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Eur J Pediatr. 2025 Mar 17;184(4):254. doi: 10.1007/s00431-025-06077-w.
The gonadotropin-releasing hormone (GnRH) stimulation test is essential for diagnosing idiopathic central precocious puberty (ICPP). Research provided that luteinizing hormone (LH) levels during the test are lower in overweight and obese girls. This study aims to establish diagnostic cut-off values in the GnRH stimulation test specifically for overweight and obese girls with ICPP. Retrospective data from 925 girls diagnosed with ICPP or premature thelarche (PT) who underwent GnRH testing were analyzed. Patients were categorized into normal weight (NW) and overweight/obese (OW) groups based on Body Mass Index Standard Deviation Score (BMI-SDS), with BMI-SDS ≥ 1 indicating OW. Only patients with Tanner stage 2 or 3 breast development were included. The mean age at diagnosis was 7.9 ± 1.1 years in ICPP and 6.4 ± 1.4 years in PT. Among the patients, 455 (49.2%) were OW. In the OW-ICPP group, the peak LH cut-off was 3.56 IU/L (AUC:0.733; sensitivity:69.2%, specificity:64%), and the peak LH/FSH ratio was 0.29 (AUC:0.828; sensitivity:77.1%, specificity:76.3%). For NW patients, the peak LH cut-off was 4.75 IU/L (AUC:0.809; sensitivity:77.1%, specificity:70.7%), and the peak LH/FSH ratio was 0.3 (AUC:0.926; sensitivity: 86.3%, specificity: 86%). In the peak LH cut-off model, the multivariate analysis identified BMI-SDS as a significant negative predictor (OR:0.585, 95%CI: 0.477-0.717, p < 0.001), showing a strong inverse relationship. Similarly, in the peak LH/FSH ratio model, BMI-SDS remained a significant negative predictor (OR: 0.744, 95% CI: 0.614-0.902, p < 0.001).
In this study, gonadotropin responses during the GnRH stimulation test were lower in overweight and obese girls with Tanner stage 2 and 3 ICPP compared to standard thresholds. It is important to utilize the GnRH test alongside clinical findings when diagnosing these patients, as responses below standard values do not rule out precocious puberty. This highlights the need for tailored diagnostic criteria to ensure timely and accurate diagnosis in this population.
• Obesity is a risk factor for early puberty.
• In girls with idiopathic central precocious puberty, obesity leads to lower values in the GnRH stimulation test compared to normal ranges. This may result in missed diagnoses, emphasizing the need to evaluate cases thoroughly with clinical data.
促性腺激素释放激素（GnRH）刺激试验对于诊断特发性中枢性性早熟（ICPP）至关重要。研究表明，超重和肥胖女孩在该试验期间的促黄体生成素（LH）水平较低。本研究旨在确定GnRH刺激试验中针对超重和肥胖ICPP女孩的诊断临界值。分析了925名诊断为ICPP或乳房过早发育（PT）且接受GnRH检测的女孩的回顾性数据。根据体重指数标准差评分（BMI-SDS）将患者分为正常体重（NW）组和超重/肥胖（OW）组，BMI-SDS≥1表示OW。仅纳入乳房发育处于坦纳2期或3期的患者。ICPP患者的诊断平均年龄为7.9±1.1岁，PT患者为6.4±1.4岁。患者中455名（49.2%）为OW。在OW-ICPP组中，LH峰值临界值为3.56 IU/L（AUC：0.733；敏感性：69.2%，特异性：64%），LH/FSH峰值比值为0.29（AUC：0.8.8；敏感性：77.1%，特异性：76.3%）。对于NW患者，LH峰值临界值为4.75 IU/L（AUC：0.809；敏感性：77.1%，特异性：70.7%），LH/FSH峰值比值为0.3（AUC：0.926；敏感性：86.3%，特异性：86%）。在LH峰值临界值模型中，多变量分析确定BMI-SDS为显著的负向预测因子（OR：0.585，95%CI：0.根据体重指数标准差评分（BMI-SDS）将患者分为正常体重（NW）组和超重/肥胖（OW）组，BMI-SDS≥1表示OW。仅纳入乳房发育处于坦纳2期或3期的患者。ICPP患者的诊断平均年龄为7.9±1.1岁，PT患者为6.4±1.4岁。患者中455名（49.2%）为OW。在OW-ICPP组中，LH峰值临界值为3.56 IU/L（AUC：0.733；敏感性：69.2%，特异性：64%），LH/FSH峰值比值为0.29（AUC：0.828；敏感性：77.1%，特异性：76.3%）。对于NW患者，LH峰值临界值为4.75 IU/L（AUC：0.809；敏感性：77.1%，特异性：70.7%），LH/FSH峰值比值为0.3（AUC：0.926；敏感性：86.3%，特异性：86%）。在LH峰值临界值模型中，多变量分析确定BMI-SDS为显著的负向预测因子（OR：0.585，95%CI：0.477 - 0.717，p＜0.001），显示出强烈的负相关关系。同样，在LH/FSH峰值比值模型中，BMI-SDS仍然是显著的负向预测因子（OR：0.744，95%CI：0.614 - 0.902，p＜0.001）。
在本研究中，与标准阈值相比，处于坦纳2期和3期ICPP的超重和肥胖女孩在GnRH刺激试验期间的促性腺激素反应较低。在诊断这些患者时，将GnRH试验与临床发现结合使用很重要，因为低于标准值的反应不能排除性早熟。这突出了需要制定针对性的诊断标准，以确保对该人群进行及时准确的诊断。
• 肥胖是性早熟的一个风险因素。
• 在特发性中枢性性早熟女孩中，与正常范围相比，肥胖导致GnRH刺激试验中的值较低。这可能导致漏诊，强调需要结合临床数据对病例进行全面评估。
