Rappaport R, Mugnier E, Limoni C, Crosnier H, Czernichow P, Leger J, Limal J M, Rochiccioli P, Soskin S
Pediatric Endocrinology Unit, Hôpital des Enfants Malades, Paris, France.
J Clin Endocrinol Metab. 1997 Feb;82(2):452-6. doi: 10.1210/jcem.82.2.3756.
The aim of the study was to assess the efficacy of GH therapy in GH-deficient children treated before the age of 3 yr. A noncomparative multicenter prospective study included 49 children (22 girls and 27 boys) with isolated GH deficiency (n = 19) or multiple pituitary hormone deficiency (n = 30) treated with daily s.c. injections (0.6 U/kg.week) for 3-5 yr. They were divided into two groups according to their height SD score for chronological age (CA) at the initiation of therapy: group A consisted of 8 patients presenting an initial height within the normal range (< 2 SD below the mean) followed for 2-5 yr, and group B consisted of 25 children followed for 5 yr among 41 patients with initial growth retardation. In group A, the mean height SD score increased from -1.1 +/- 0.6 to 0.35 +/- 1.0 SD (P < 0.001) in the first year and remained in the normal range throughout the following 4 yr. In group B after 4 yr of treatment, the mean height SD score for age had increased from -3.6 +/- 1.0 SD (time zero) to -0.9 +/- 1.2 SD. During the fourth year of therapy, the mean height gain of 0.2 +/- 0.2 SD was significant (P < 0.001). After 5 yr of treatment, a plateau was reached with a corresponding height SD score (CA) of -0.8 +/- 1.2 SD (95% confidence interval between -1.3 and -0.2 SD). This value remained significantly below normal for age (P < 0.001), indicating that catch-up growth was incomplete. Only four patients (16%) remained below -2SD for CA. The 5-yr height gain was negatively correlated with the height SD score at the start of treatment (r = -0.6; P < 0.005) and the first year height gain was the most predictive parameter. There was no significant influence of intrauterine growth retardation, body mass index and age at the start of treatment, or parental target height. Bone maturation was significantly retarded over CA by a mean value of 1.1 +/- 0.9 yr (P < 0.0001), with a mean bone age/CA ratio of 0.8 +/- 0.2 after a mean treatment duration of 5.1 +/- 1.1 yr. In conclusion, the rapid and almost complete return to normal height obtained in this study supports the need for GH treatment in early diagnosed GH-deficient children. The present dosage may be considered the minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for these children. In addition, it allowed growth at a rate normal for age in patients diagnosed before growth retardation.
本研究的目的是评估生长激素（GH）治疗对3岁前开始治疗的生长激素缺乏儿童的疗效。一项非对照多中心前瞻性研究纳入了49例儿童（22例女孩和27例男孩），这些儿童患有孤立性生长激素缺乏（n = 19）或多种垂体激素缺乏（n = 30），接受每日皮下注射（0.6 U/kg·周）治疗3至5年。根据治疗开始时按实足年龄（CA）计算的身高标准差评分，将他们分为两组：A组由8例初始身高在正常范围内（低于平均值2个标准差以下）的患者组成，随访2至5年；B组由41例初始生长迟缓患者中的25例随访5年的儿童组成。在A组中，第一年平均身高标准差评分从-1.1±0.6增加到0.35±1.0标准差（P < 0.001），并在随后4年中一直保持在正常范围内。在B组治疗4年后，年龄别平均身高标准差评分从-3.6±1.0标准差（时间零点）增加到-0.9±1.2标准差。在治疗的第四年，平均身高增长0.2±0.2标准差具有显著性（P < 0.001）。治疗5年后，达到一个平台期，相应的身高标准差评分（CA）为-0.8±1.2标准差（95%置信区间在-1.3和-0.2标准差之间）。该值仍显著低于年龄别正常范围（P < 0.001），表明追赶生长不完全。只有4例患者（16%）的身高仍低于CA的-2个标准差。5年身高增长与治疗开始时的身高标准差评分呈负相关（r = -0.6；P < 0.005），第一年身高增长是最具预测性的参数。宫内生长迟缓、治疗开始时的体重指数和年龄或父母的目标身高均无显著影响。骨成熟明显落后于CA，平均落后1.1±0.9岁（P < 0.0001），在平均治疗5.1±1.1年后，平均骨龄/CA比值为0.8±0.2。总之，本研究中获得的快速且几乎完全恢复到正常身高支持对早期诊断的生长激素缺乏儿童进行生长激素治疗的必要性。目前的剂量可被视为获得满意追赶生长以确保这些儿童有良好结局的最低剂量。此外，它使生长迟缓前诊断的患者以年龄正常的速度生长。
