Division of Endocrinology, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts.
Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts.
J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3650-9. doi: 10.1210/clinem/dgaa475.
Children with brain tumors may have pubertal onset at an inappropriately young chronologic age. Hypothalamic-pituitary irradiation ≥18Gy has been found to be a risk factor; age at irradiation is associated with pubertal timing. However, the underlying mechanisms are unknown.
To determine the impact of body mass index (BMI) and catch-up growth on pubertal timing in females treated for medulloblastoma and other embryonal tumors.
DESIGN, SETTING, AND PATIENTS: Retrospective cohort analysis of 90 female patients treated for medulloblastoma and other embryonal tumors at Dana-Farber Cancer Institute/Boston Children's Hospital from 1996 to 2016. Eighteen individuals met inclusion criteria, with a mean ± SD follow-up period of 11.9 ± 3.4 years.
Multiple linear regression models for age at pubertal onset and bone age discrepancy from chronologic age at pubertal onset assessed the joint influences of age at irradiation, hypothalamic irradiation dose, undernutrition duration, BMI standard deviation score (SDS) at pubertal onset, and catch-up BMI SDS.
The mean ± SD age of pubertal onset was 9.2 ± 1.3 years and hypothalamic radiation dose was 31.9 ± 9.9 Gy. There was a direct relationship between age at irradiation and age at pubertal onset (β = 0.323 ± 0.144 [standard error] year per year; P = 0.04) that was significantly attenuated after adjusting for BMI SDS at pubertal onset (P = 0.5) and catch-up BMI SDS (P = 0.08), suggesting that BMI is a mediator.
Both absolute and catch-up BMI SDS at pubertal onset are significant mediators of pubertal timing and bone age discrepancy in pediatric medulloblastoma and other embryonal tumors, and thus, are targetable risk factors to optimize pubertal timing.
患有脑肿瘤的儿童可能会在不合适的生理年龄过早进入青春期。已经发现,下丘脑-垂体照射≥18Gy 是一个风险因素;照射时的年龄与青春期开始的时间有关。然而,其潜在机制尚不清楚。
确定体重指数(BMI)和追赶生长对接受髓母细胞瘤和其他胚胎性肿瘤治疗的女性青春期开始时间的影响。
设计、地点和患者:回顾性队列分析了 1996 年至 2016 年在丹娜-法伯癌症研究所/波士顿儿童医院接受髓母细胞瘤和其他胚胎性肿瘤治疗的 90 名女性患者。18 人符合纳入标准,平均随访期为 11.9±3.4 年。
采用多元线性回归模型,对青春期开始年龄和骨龄与青春期开始时的生理年龄之间的差异进行分析,评估照射年龄、下丘脑照射剂量、营养不良持续时间、青春期开始时的 BMI 标准差评分(SDS)和追赶 BMI SDS 的联合影响。
青春期开始的平均年龄为 9.2±1.3 岁,下丘脑照射剂量为 31.9±9.9Gy。照射年龄与青春期开始年龄之间存在直接关系(β=0.323±0.144[标准误差]每增加 1 年增加 0.323 岁;P=0.04),但在调整青春期开始时的 BMI SDS(P=0.5)和追赶 BMI SDS(P=0.08)后,这种关系显著减弱,提示 BMI 是一个中介因素。
青春期开始时的绝对 BMI SDS 和追赶 BMI SDS 均是儿科髓母细胞瘤和其他胚胎性肿瘤青春期开始时间和骨龄差异的重要中介因素,因此,是可优化青春期开始时间的靶向风险因素。