Brauner R, Adan L, Souberbielle J C, Esperou H, Michon J, Devergie A, Gluckman E, Zucker J M
Pediatric Endocrinology Unit, Université Paris V, France.
J Pediatr. 1997 May;130(5):785-92. doi: 10.1016/s0022-3476(97)80022-4.
Conditioning for bone marrow transplantation (BMT) by total body irradiation frequently causes growth failure. The contribution of growth hormone (GH) deficiency to this failure was assessed in 38 patients given three types of body irradiation: group 1 (n = 18) was given 12 Gy total body irradiation as six fractions, group 2 (n = 14) 10 Gy (one dose) total body irradiation, and group 3 (n = 6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the hypothalamic-pituitary area. At the first evaluation, 2.9 +/- 0.2 (SE) years after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but significantly greater in group 3 (p < 0.02 for IGF-I and 0.01 for IGFBP-3). These values were similar in those patients in groups 1 and 2 who had low GH peaks after stimulation (12 patients: IGF-I, 0.8 +/- 0.2 U/ml; IGFBP-3, 1.6 +/- 0.2 mg/L) and in those with normal GH peaks (20 patients: 1 +/- 0.1 U/ml and 1.8 +/- 0.1 mg/L). The decrease in height 2 years after BMT was significantly (p < 0.01) greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar in groups 1 and 2 (0.9 +/- 0.2 and 1.4 +/- 0.3 SD), significantly (p < 0.05) greater in group 2 than in group 3 (0.7 +/- 0.2 SD). The individual height changes between BMT and the last clinical evaluation before GH therapy were not correlated with the age at BMT, GH peak after stimulation, plasma IGF-I concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were given GH therapy; their growth rate became normal for age (-2.1 +/- 0.9 SDS before and -0.2 +/- 0.4 SDS for the first year; not significant) without any catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no diagnostic value for GH deficiency after TBI. Their normal or high levels, despite low GH peaks, suggest that bone irradiation induces lesions causing resistance to IGF-I.
全身照射用于骨髓移植（BMT）预处理时常常导致生长障碍。对38例接受三种类型身体照射的患者评估了生长激素（GH）缺乏对这种生长障碍的影响：第1组（n = 18）接受12 Gy全身照射，分6次给予；第2组（n = 14）接受10 Gy（单次剂量）全身照射；第3组（n = 6）接受6 Gy（单次剂量）胸腹照射，该照射不涉及下丘脑 - 垂体区域。在首次评估时，即BMT后2.9±0.2（SE）年，第1组和第2组的血浆胰岛素样生长因子I（IGF - I）及其GH依赖性结合蛋白（IGFBP - 3）值相似，但第3组显著更高（IGF - I p < 0.02，IGFBP - 3 p < 0.01）。第1组和第2组中刺激后GH峰值低的患者（12例：IGF - I，0.8±0.2 U/ml；IGFBP - 3，1.6±0.2 mg/L）与GH峰值正常的患者（20例：1±0.1 U/ml和1.8±0.1 mg/L）的这些值相似。BMT后2年，第2组身高下降显著（p < 0.01）大于第1组和第3组，但BMT后5年，第1组和第2组相似（0.9±0.2和1.4±0.3 SD），第2组显著（p < 0.05）大于第3组（0.7±0.2 SD）。BMT与GH治疗前最后一次临床评估之间的个体身高变化与BMT时的年龄、刺激后GH峰值、血浆IGF - I浓度或IGFBP - 3浓度均无相关性。7例GH缺乏患者接受了GH治疗；他们的生长速率达到年龄正常水平（治疗前 - 2.1±0.9 SDS，第一年 - 0.2±0.4 SDS；无显著差异），但无任何追赶生长。我们得出结论，血浆IGF - I和IGFBP - 3值对TBI后GH缺乏无诊断价值。尽管GH峰值低，但它们的正常或高水平表明骨照射诱导了导致对IGF - I产生抵抗的病变。
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