中枢性性早熟儿童的最终成人身高 - 一项回顾性研究。
Final adult height in children with central precocious puberty - a retrospective study.
机构信息
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Centre for Health Informatics and Statistics, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia.
出版信息
Front Endocrinol (Lausanne). 2022 Dec 2;13:1008474. doi: 10.3389/fendo.2022.1008474. eCollection 2022.
BACKGROUND/AIMS: Central precocious puberty (CPP) is due to premature activation of the hypothalamic-pituitary-gonadal axis. It predominantly affects girls. CPP leads to lower final height (FH), yet the treatment benefit in girls between 6 and 8 years is equivocal. Our main goal was to evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) on FH and identify factors that predict FH.
METHODS
In a retrospective study, children with CPP (12 boys, 81 girls) that reached FH were included. Their clinical data at diagnosis and up to their final height was compared by descriptive statistics among idiopathic (iCPP) (n=68) and non-idiopathic CPP (nCPP) and between GnRHa treated (n=48) and untreated (n=15) girls with iCPP. The treatment effect of body weight (BW) adjusted GnRHa dosing was evaluated. Univariate linear regression and step-wise multivariable regression including 48 girls with iCPP treated with GnRHa were performed to identify predicting factors for FH.
RESULTS
Children with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0 cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5 cm in treated, 161.0 cm in untreated girls with iCPP), although the onset of menarche was 2.5 years earlier among untreated girls. BW-adjusted dosing suppressed peak luteinizing hormone (LH) below 4.5 IU/L in 95% of children; however, bone age further advanced during therapy in 38% of patients. Predicting factors revealed by multivariable regression were bone age at diagnosis, BMI SDS at diagnosis, LH basal, age at start and cessation of treatment, predicted adult height and target height. (R2 = 0.72).
CONCLUSION
Children with nCPP had worse FH outcome compared to iCPP despite similar CPP onset and therapeutic characteristics. Treatment by GnRHa using BW-adjusted dosing was effective in delaying menarche onset and reaching target height in girls with iCPP. Multiple factors affecting FH outcome indicated individualized decision-making regarding therapeutic intervention remains challenging. In the treated patients, among the factors that can be influenced, height at treatment cessation most significantly influenced the outcome.
背景/目的：中枢性性早熟（CPP）是由于下丘脑-垂体-性腺轴过早激活所致。它主要影响女孩。CPP 会导致最终身高（FH）降低，但 6 至 8 岁女孩的治疗益处尚存在争议。我们的主要目标是评估促性腺激素释放激素类似物（GnRHa）对 FH 的影响，并确定预测 FH 的因素。
方法
在一项回顾性研究中，纳入了达到 FH 的 CPP 患儿（12 名男孩，81 名女孩）。通过描述性统计比较了特发性 CPP（iCPP）（n=68）和非特发性 CPP（nCPP）患儿以及接受 GnRHa 治疗（n=48）和未接受治疗（n=15）的 iCPP 女孩的诊断时和 FH 时的临床数据。评估了体重（BW）调整后的 GnRHa 剂量的治疗效果。对接受 GnRHa 治疗的 48 名 iCPP 女孩进行了单变量线性回归和逐步多变量回归，以确定 FH 的预测因素。
结果
特发性 CPP（iCPP）患儿的 FH 更高（p=0.002），而非特发性 CPP 患儿的 FH 更低。诊断后，治疗组比未治疗组多增加了 7.0cm。然而，由于个体化决策，两组的 FH 相当（接受治疗的女孩为 161.5cm，未接受治疗的 iCPP 女孩为 161.0cm），尽管未接受治疗的女孩的初潮年龄早了 2.5 年。BW 调整后的剂量使 95%的儿童的峰值黄体生成素（LH）低于 4.5IU/L；然而，在治疗期间，38%的患者骨龄进一步进展。多变量回归显示的预测因素包括诊断时的骨龄、诊断时的 BMI SDS、LH 基础值、治疗开始和停止年龄、预测成人身高和目标身高。（R2=0.72）。
结论
与 iCPP 相比，nCPP 患儿的 FH 结局更差，尽管 CPP 发病和治疗特征相似。使用 BW 调整后的剂量进行 GnRHa 治疗可有效延迟初潮发作并达到 iCPP 女孩的目标身高。影响 FH 结局的多种因素表明，治疗干预的个体化决策仍然具有挑战性。在接受治疗的患者中，在可影响的因素中，治疗结束时的身高对结局的影响最大。
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