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基于 GnRH 激动剂治疗期间预测的成年身高变化来制定女童中枢性性早熟个体化治疗决策。

Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty.

机构信息

Department of Pediatrics, University of California San Diego, and Rady Children's Hospital, San Diego, CA, USA.

Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Penn State Hershey Medical Center, Hershey, PA, USA.

出版信息

J Pediatr Endocrinol Metab. 2022 Dec 5;36(3):299-308. doi: 10.1515/jpem-2022-0476. Print 2023 Mar 28.

Abstract

OBJECTIVES

It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care.

METHODS

Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models.

RESULTS

BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months).

CONCLUSIONS

These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH.

摘要

目的

了解哪些变量会影响中枢性性早熟(CPP)患儿在促性腺激素释放激素类似物(GnRHa)治疗过程中预测成年身高(PAH)的变化,对于个体化治疗决策和优化治疗至关重要。

方法

对 77 例接受醋酸亮丙瑞林治疗的 CPP 女孩在治疗过程中的 PAH、实际年龄(CA)、骨龄(BA)、BA/CA 和身高速度(HV)变化进行评估。第二次分析重点关注 BA 首次观察到≥12 岁前的 3 年变化。采用图形检查和线性混合效应分析来描述相关性。采用多元线性回归模型来检验治疗持续时间与最后评估的 PAH 之间的关系。

结果

BA/CA 和 HV 在治疗过程中呈非线性变化,前 6-18 个月 PAH 变化最大,改善最明显。BA 起始年龄较小的女孩,BA 进展速度趋于更慢下降。PAH 的治疗期间变化与同时的 BA/CA 变化、HV 和 BA 以及治疗开始时的 CA 有关。最后评估的 PAH 与较长的治疗持续时间(主要/探索性模型的截止值为≥33/≥55 个月)呈正相关。

结论

这些发现支持 GnRHa 治疗期间的个体化监测。初始反应应谨慎解释,直到治疗开始后 6-18 个月,并且不应根据起始治疗年龄较小的女孩骨成熟持续进展来推断治疗失败。不应自动基于 PAH 或 HV 变化的减少而停止治疗,因为持续治疗可能会导致 PAH 持续增加或维持。

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