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儿童脑肿瘤放疗后幸存者的诊断前和诊断后生长发育迟缓、成年后身材矮小和未治疗的生长激素缺乏。

Pre- and postdiagnosis growth failure, adult short stature, and untreated growth hormone deficiency in radiotherapy-treated long-term survivors of childhood brain tumor.

机构信息

Department of Pediatrics and Adolescence, PEDEGO Research Unit and Medical Research Center, University and University Hospital of Oulu, Oulu, Finland.

Department of Pediatrics and Adolescence, Helsinki University Hospital, Helsinki, Finland.

出版信息

PLoS One. 2022 Sep 6;17(9):e0274274. doi: 10.1371/journal.pone.0274274. eCollection 2022.

Abstract

PURPOSE

Growth failure is common in radiotherapy-treated long-term survivors of pediatric brain tumors, but studies on longitudinal growth in this patient group are lacking. Here, the aim was to assess the changes in growth patterns before and after brain tumor diagnosis, the adult height, and the risk factors for compromised growth. The incidence and treatment practices of growth hormone deficiency were analyzed.

METHODS

A cohort of 73 survivors of childhood brain tumor (median age 27.2 years, range 16.2 to 43.8 years) was studied after a median follow-up period of 20.4 years from diagnosis (IQR 14.9 to 22.9 years). Patients were treated in five university hospitals in Finland between 1970 and 2008. Growth curves, final height, and patient- and disease-related risk factors for compromised growth during different growth periods were analyzed. Laboratory analyses for IGF-1 and IGFBP-3 were performed at the follow-up.

RESULTS

Growth failure was evident at diagnosis, with a mean height decline of -0.6 SDS (standard deviation score) from birth (95% CI -1.15 to -0.05). Mean height SDS decline after the diagnosis was -1.09 SDS (95%CI -1.51 to -0.66). At follow-up, 37% of the study subjects (27/73) had true short stature (height < -2 SDS). The mean height deficit corrected for target height was -1.9 SDS (95% CI -1.45 to -2.40). Growth failure was associated with the age at diagnosis, corticosteroid dose, radiotherapy modality and mean dose of irradiation in the thalamic area. Low IGF-1 level (below -2.0 SDS) was found in 32% (23/72), and untreated growth hormone deficiency in 40% (29/72) of the subjects.

CONCLUSION

Longitudinal growth impairment was common in radiotherapy-treated survivors of childhood brain tumor, resulting in compromised adult height. Loss of growth potential was evident already at diagnosis and further accelerated by the treatments. At young adulthood, unrecognized growth hormone deficiency was common.

摘要

目的

放疗治疗的儿科脑肿瘤长期幸存者中常出现生长发育迟缓,但针对该患者群体的纵向生长研究较为缺乏。本研究旨在评估脑肿瘤诊断前后生长模式的变化、成年身高以及影响生长发育的风险因素。同时分析生长激素缺乏症的发生率和治疗方法。

方法

研究纳入了 73 例儿童脑肿瘤幸存者(中位年龄 27.2 岁,范围 16.2 岁至 43.8 岁),自诊断起中位随访时间为 20.4 年(IQR 14.9 年至 22.9 年)。这些患者于 1970 年至 2008 年在芬兰的五所大学附属医院接受治疗。分析了生长曲线、最终身高以及不同生长时期影响生长发育的患者和疾病相关风险因素。在随访时进行 IGF-1 和 IGFBP-3 的实验室检测。

结果

诊断时即出现生长发育迟缓,出生时身高的平均下降值为-0.6 SDS(标准偏差评分)(95%CI-1.15 至-0.05)。诊断后平均身高 SDS 下降值为-1.09 SDS(95%CI-1.51 至-0.66)。随访时,37%(27/73)的研究对象存在真正的身材矮小(身高<-2 SDS)。根据目标身高校正后的平均身高缺陷值为-1.9 SDS(95%CI-1.45 至-2.40)。生长发育迟缓与诊断时的年龄、皮质类固醇剂量、放疗方式以及丘脑区域的平均照射剂量相关。23/72(32%)的受试者 IGF-1 水平较低(低于-2.0 SDS),29/72(40%)的受试者未治疗的生长激素缺乏症。

结论

放疗治疗的儿童脑肿瘤幸存者中,纵向生长受损较为常见,导致成年身高受损。在诊断时已经出现生长潜能的丧失,且进一步因治疗而加速。在年轻成年时,生长激素缺乏症未被识别较为常见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bd5/9447887/04a484769804/pone.0274274.g001.jpg

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