Balducci R, Toscano V, Mangiantini A, Municchi G, Vaccaro F, Picone S, Di Rito A, Boscherini B
Department of Pediatrics, University Tor Vergata, Rome, Italy.
J Clin Endocrinol Metab. 1995 Dec;80(12):3596-600. doi: 10.1210/jcem.80.12.8530605.
GnRH analog associated with GH therapy has potential importance for treatment of short stature in subjects without GH deficiency and with a normal onset of puberty. We treated 10 girls with familial short stature with the GnRH analog leuprolide (3.75 mg, im, every 25 days) and GH (0.1 IU/kg.day, sc, 6 days/week). The combined therapies were started simultaneously, and the patients were treated for 28.1 +/- 5.4 (range, 24-36) months. At the onset of treatment, chronological age was 11.6 +/- 1.4 yr, bone age was 10.6 +/- 0.9 yr, height was -2.7 +/- 0.7 SD, predicted height (PH; Bayley-Pinneau score) was 143.2 +/- 3 cm. Target height was 147.6 +/- 5.6 cm. Tanner stage was II-III for breast and genitalia. During treatment, puberty was completely suppressed in all patients. Statistical analysis was performed using Student's t test for paired data. After 12 months of treatment, we observed a significant (P < 0.02) improvement of predicted height (146.2 +/- 3.4 cm). This improvement remained significant (147.6 +/- 3.5; P < 0.001) when treatment was withdrawn. At that time, chronological age was 13.9 +/- 1.2 yr, and bone age was 12.4 +/- 0.7 yr. At the present time (3 +/- 0.97 yr after discontinuation), all of the girls have reached a final height of 144.6 +/- 3 cm (range, 140-149.3 cm). The final height is not significantly different compared with the PH at the beginning of treatment or with target height. These data show that in our patients, combined treatment with GnRH analog and GH, despite a significant improvement in PH during therapy and upon its withdrawal, does not result in a significant increase in adult stature. Larger and perhaps more prolonged studies in patients of both sexes are required to reach definitive conclusions. Nevertheless, the cost of this treatment in terms of both subject compliance and economic cost should be weighed against the small height gain, if any, that may be achieved.
促性腺激素释放激素(GnRH)类似物联合生长激素(GH)治疗对于非生长激素缺乏且青春期正常启动的身材矮小患者具有潜在重要意义。我们对10名家族性身材矮小的女孩使用GnRH类似物亮丙瑞林(3.75毫克,肌肉注射,每25天一次)和生长激素(0.1国际单位/千克·天,皮下注射,每周6天)进行治疗。联合治疗同时开始,患者接受治疗28.1±5.4(范围24 - 36)个月。治疗开始时,实际年龄为11.6±1.4岁,骨龄为10.6±0.9岁,身高低于平均身高2.7±0.7标准差,预测身高(PH;贝利 - 皮诺评分)为143.2±3厘米。靶身高为147.6±5.6厘米。乳房和生殖器的坦纳分期为II - III期。治疗期间,所有患者的青春期均被完全抑制。采用配对数据的学生t检验进行统计分析。治疗12个月后,我们观察到预测身高有显著(P < 0.02)改善(146.2±3.4厘米)。停止治疗时,这种改善仍然显著(147.6±3.5;P < 0.001)。此时,实际年龄为13.9±1.2岁,骨龄为12.4±0.7岁。目前(停药后3±0.97年),所有女孩的最终身高达到144.6±3厘米(范围140 - 149.3厘米)。最终身高与治疗开始时的预测身高或靶身高相比无显著差异。这些数据表明,在我们的患者中,GnRH类似物和生长激素联合治疗尽管在治疗期间和停药时预测身高有显著改善,但并未导致成人身高显著增加。需要对更多男女患者进行更大规模且可能更长时间的研究才能得出明确结论。然而,这种治疗在患者依从性和经济成本方面的代价应与可能实现的微小身高增长(如果有的话)相权衡。