The effect of obesity on the GnRH stimulation test in girls with idiopathic central precocious puberty.

Abstract

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).

Conclusion: 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.

What is known: • Obesity is a risk factor for early puberty.

What is new: • 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.