Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Cancer. 2019 May 15;125(10):1748-1755. doi: 10.1002/cncr.31975. Epub 2019 Jan 28.
The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT).
Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models.
Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes.
Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD.
儿童期急性淋巴细胞白血病（ALL）幸存者的生长激素缺乏症（GHD）对神经认知功能的影响知之甚少。本研究通过调整颅放射治疗（CRT），考察了 GHD 对功能结果的贡献。
共纳入 571 名 ALL 成年幸存者（49%为女性；平均年龄 37.4 岁；年龄范围 19.4-62.2 岁），他们完成了神经认知测试以及神经认知症状、情绪困扰和生活质量的自我报告。GHD 的定义为之前诊断为 GHD 或在神经认知测试时，生长激素刺激试验后血清胰岛素样生长因子 1 水平低于性别和年龄的-2.0 个标准差。甲状腺功能减退症、性腺功能减退症、性别、诊断时年龄、CRT 剂量、鞘内和高剂量静脉甲氨蝶呤作为多变量线性回归模型的协变量。
在 571 名幸存者中，有 298 名（52%）患有 GHD，且患有 GHD 的幸存者接受了更高剂量的 CRT（P=0.002）。无论是否接受过生长激素治疗，患有 GHD 的幸存者在词汇（Z 评分：-0.84 对-0.61；P=0.02）、处理速度（Z 评分：-0.49 对-0.30；P=0.04）、认知灵活性（Z 评分：-1.37 对-0.94；P=0.01）和语言流畅性（Z 评分：-0.74 对-0.44；P=0.001）方面表现更差，且与未患有 GHD 的幸存者相比，他们自我报告的神经认知问题更多，生活质量更差。多变量和中介模型显示，GHD 与生活质量的较小影响相关（一般健康，P=0.01；活力，P=0.01；心理健康，P=0.01）；而 CRT 剂量决定了较差的神经认知结果。
接受 CRT 的儿童期 ALL 幸存者存在发生 GHD 的风险，尽管神经认知结果不佳是由 CRT 剂量决定的，而不是由 GHD 引起的。
