Introduction: Children with self-limited delayed puberty (constitutional delay) enter puberty after variable waiting times, and the factors associated with their eventual pubertal timing are not well understood. Methods: We conducted a retrospective study of 99 girls and 228 boys with self-limited delayed puberty (DP) at an academic medical center between 2000 and 2015. To define features and potential subtypes of self-limited DP, we performed group-based trajectory modeling on childhood growth and latent-variable factor analysis on clinical characteristics. We then conducted time-to-event analyses to identify associations with pubertal timing. Results: We identified two distinct growth trajectories in individuals with self-limited DP: one with stable and the other with declining height percentiles. Latent-variable factor analysis identified five factors underlying clinical variation that appear to correspond to genetic height potential, body mass index, childhood growth, parental pubertal delay, and medical issues (attention-deficit/hyperactivity disorder and inhaled glucocorticoid use). We observed correlations between pubertal timing and bone age (p=0.01), childhood height (p=0.004), and midparental target height (p<0.001), but not with parental pubertal delay or with testosterone treatment in boys. Conclusions: By illustrating the heterogeneity within self-limited DP and identifying factors underlying this heterogeneity, our study suggests that there may be multiple causes of self-limited DP. However, our ability to determine when puberty will eventually occur remains limited. Dissecting self-limited DP into its component subtypes may inform future studies of the mechanisms contributing to pubertal delay as well as studies of the short- and long-term outcomes of self-limited DP.


中文翻译：

---

在自限性青春期延迟中识别与青春期时间相关的因素的方法

简介：患有自限性青春期延迟（体质性延迟）的儿童在等待时间可变后进入青春期，与他们最终进入青春期时间相关的因素尚不清楚。方法：我们对 2000 年至 2015 年间在一家学术医学中心患有自限性青春期延迟 (DP) 的 99 名女孩和 228 名男孩进行了回顾性研究。为了定义自限性 DP 的特征和潜在亚型，我们进行了基于组的轨迹儿童生长建模和临床特征的潜变量因素分析。然后，我们进行了事件发生时间分析，以确定与青春期时间的关联。结果：我们在自限性 DP 患者中确定了两条截然不同的生长轨迹：一条稳定，另一条身高百分位数下降。潜变量因素分析确定了临床变异的五个潜在因素，这些因素似乎与遗传身高潜力、体重指数、儿童生长、父母青春期延迟和医疗问题（注意力缺陷/多动障碍和吸入糖皮质激素的使用）相对应。我们观察到青春期时间与骨龄 (p=0.01)、儿童身高 (p=0.004) 和父母目标身高中值 (p<0.001) 之间的相关性，但与男孩的父母青春期延迟或睾酮治疗无关。结论：通过说明自限性 DP 内的异质性并确定这种异质性背后的因素，我们的研究表明自限性 DP 可能有多种原因。然而，我们确定青春期最终何时到来的能力仍然有限。