Brennan B M, Rahim A, Mackie E M, Eden O B, Shalet S M
Department of Paediatric Oncology, Royal Manchester Children's Hospital, UK.
Clin Endocrinol (Oxf). 1998 Jun;48(6):777-83. doi: 10.1046/j.1365-2265.1998.00438.x.
Growth hormone status was assessed in a cohort of 32 (16 male) adults who had received cranial irradiation (XRT) in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL) and compared with 35 age matched young adults (18 male).
Height and weight were measured in all subjects and the heights of the patients at XRT were obtained from their case notes. Each patient and control underwent two provocative tests of growth hormone (GH) secretion using insulin (0.2 IU/kg body weight) and arginine (20 g/m2). Basal serum insulin like growth factor-1 (IGF-1) and IGFBP-3 (binding protein-3) concentrations were also measured.
The patient group had a significantly lower peak GH response to both provocative tests (P < 0.01), and lower IGF-1 and IGFBP-3 levels compared with the normal controls (P < 0.01). Nine of the patient group were severely GH deficient (peak GH response < 9 mU/l to both provocative agents) and a further 12 patients were GH insufficient (peak GH response < 20 mU/l to both tests with at least one peak GH response > 9 mU/l). Overall a significant median change in height from XRT to final height of -0.5 SDS was found which was even greater in the severely GH deficient group (median change in height of -2.1 SDS).
These data suggest that a significant proportion of adults treated with cranial XRT in childhood with irradiation doses between 18-25 Gy, as part of their treatment for ALL, are severely GH deficient now and should be considered for GH replacement. Changes in GH secretion evolve with time following irradiation-induced damage to the hypothalamic-pituitary axis; therefore long-term surveillance will be required in those remaining patients, in whom GH status is considered currently to be insufficient or even normal.
对32名（16名男性）在儿童期接受过颅脑照射（XRT）作为急性淋巴细胞白血病（ALL）治疗一部分的成年人的生长激素状况进行评估，并与35名年龄匹配的年轻成年人（18名男性）进行比较。
测量所有受试者的身高和体重，并从病历中获取患者接受XRT时的身高。每位患者和对照者均接受两次生长激素（GH）分泌激发试验，分别使用胰岛素（0.2 IU/kg体重）和精氨酸（20 g/m²）。同时测量基础血清胰岛素样生长因子-1（IGF-1）和IGFBP-3（结合蛋白-3）浓度。
与正常对照组相比，患者组对两种激发试验的GH峰值反应均显著降低（P < 0.01），IGF-1和IGFBP-3水平也较低（P < 0.01）。患者组中有9人严重GH缺乏（对两种激发剂的GH峰值反应均< 9 mU/l），另有12名患者GH分泌不足（对两种试验的GH峰值反应均< 20 mU/l，且至少有一次GH峰值反应> 9 mU/l）。总体而言，发现从XRT到最终身高的中位数显著变化为-0.5 SDS，在严重GH缺乏组中变化更大（身高中位数变化为-2.1 SDS）。
这些数据表明，作为ALL治疗的一部分，在儿童期接受18 - 25 Gy照射剂量的颅脑XRT治疗的成年人中，有很大一部分目前严重GH缺乏，应考虑进行GH替代治疗。GH分泌的变化在照射引起下丘脑-垂体轴损伤后随时间演变；因此，对于目前认为GH状况不足甚至正常的其余患者，需要进行长期监测。
