Cacciari E, Cicognani A, Pirazzoli P, Zucchini S, Salardi S, Balsamo A, Cassio A, Pasini A, Carlá G, Tassinari D, Gualandi S
Department of Pediatrics, University of Bologna, Italy.
Eur J Endocrinol. 1997 Jul;137(1):53-60. doi: 10.1530/eje.0.1370053.
The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated. The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) -2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal GH secretion was also evaluated. In the treated subjects final height SDS was higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P = 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty. When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment.
本研究的目的是回顾性评估各种生长学和实验室参数对一组生长激素缺乏儿童替代治疗后最终身高的影响，并将他们的最终身高与一组生长激素分泌正常因而未接受治疗的矮小儿童的最终身高进行比较。对83例（51例男性和32例女性）特发性孤立性生长激素缺乏且接受重组人生长激素（hGH）治疗2 - 7年的患者的最终身高进行了评估。治疗开始时的纳入标准为因特发性孤立性生长激素缺乏（两次药物激发试验后生长激素峰值<8微克/升和/或夜间平均生长激素浓度<3.3微克/升）导致的身材矮小（按年龄的平均身高标准差评分（SDS）为-2.21），以及通过皮下注射以每周15 - 20 U/m²的剂量进行重组hGH治疗至少2年，每周注射6或7天。诊断时的平均实际年龄为12.2±1.7岁；35例为青春期前，48例为青春期。还评估了51例生长激素分泌正常的未治疗矮小身材受试者（诊断时按年龄的平均身高SDS为-2.13）（42例男性和9例女性：诊断时29例青春期前和22例青春期，平均实际年龄11.6±2.4岁）的最终身高。治疗组受试者的最终身高SDS高于未治疗组（-1.3对-1.7 SDS；P = 0.01）。治疗组和未治疗组受试者的最终身高均低于靶身高，但治疗组39%的受试者最终身高高于靶身高，而未治疗组仅为20%（P = 0.035）。在治疗组受试者中，这一百分比在治疗最初几年身高相对于骨龄有所改善的患者中更高。虽然治疗组女性仅在靶身高与最终身高之间显示出正相关（P = 0.0001），但治疗组男性的最终身高与诊断时的贝利 - 皮诺预测值、按年龄的身高、诊断时的骨龄以及靶身高相关。青春期前开始治疗的患者在青春期开始时的数据计算中也显示出这些相关性，以及与青春期开始时的实际年龄相关。当考虑试验中生长激素反应对最终身高的影响时，根据生长激素缺乏的严重程度，超过靶身高的受试者百分比逐渐增加。青春期前或青春期开始治疗的患者在身高增长方面没有差异。我们治疗的患者获得的身高增长，无论多么微小，最终身高高于靶身高的患者数量以及与未治疗的矮小身材受试者的良好比较都代表了一个有希望的结果，通过个性化治疗可能会得到改善。
