Pasquino A M, Pucarelli I, Segni M, Matrunola M, Cerroni F
Pediatric Department, University La Sapienza, Rome, Italy.
J Clin Endocrinol Metab. 1999 Feb;84(2):449-52. doi: 10.1210/jcem.84.2.5431.
GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.
促性腺激素释放激素类似物(GnRHa)是中枢性性早熟(CPP)的首选治疗药物,因为抑制青春期发育并降低生长速度(GV)或骨成熟度(BA)应能提高成年身高。然而,在一些患者中,GV下降非常显著,以至于损害了预测成年身高(PAH);因此,建议加用生长激素(GH)。在20例特发性CPP患者中(接受GnRHa长效曲普瑞林治疗,剂量为每21天100μg/kg肌肉注射,至少治疗2 - 3年),其GV低于按实际年龄计算的第25百分位数,其中10例除GnRHa外,还接受了剂量为0.3mg/kg每周皮下注射6天、共2 - 4年的GH治疗;另外10例在BA、实际年龄和GnRHa治疗持续时间方面与之匹配,生长模式相同但拒绝GH治疗,用于评估加用GH的疗效。所有患者均无典型的生长激素缺乏。两组在相似的BA时(平均±标准误)停止治疗:GnRHa加GH组为13.2±0.2岁,对照组为13.0±0.1岁。在研究结束时,所有患者均达到成年身高。当患者前一年生长不足1cm且BA超过15岁时,视为达到成年身高。接受GH加GnRHa治疗组的成年身高显著高于治疗前的PAH(160.6±1.3 vs. 152.7±1.7cm,P < 0.001)。显著超过了靶身高(TH)。仅接受GnRH治疗组的成年身高并不显著高于治疗前的PAH(157.1±2.5 vs. 155.5±1.9cm)。仅达到了TH,但未显著超过。计算治疗前PAH与最终身高之间的厘米数增加量,GH联合GnRHa治疗的患者为7.9±1.1cm;而仅接受GnRHa治疗的患者增加量仅为1.6±1.2cm(P = 0.001)。此外,在接受GH治疗的患者中(与仅接受GnRHa治疗的患者相比),未观察到对骨龄进展、卵巢囊肿出现及妇科随访有任何副作用。总之,成年身高增加7.9cm代表了显著改善,这证明在GnRHa常规治疗期间加用GH 2 - 3年是合理的,特别是对于CPP患者以及GV下降显著以至于损害PAH、甚至达不到第三百分位数的患者。