Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, Brazil.
J Clin Endocrinol Metab. 2010 Jan;95(1):328-32. doi: 10.1210/jc.2009-1577. Epub 2009 Nov 19.
Isolated heterozygous SHOX defects are the most frequent monogenic cause of short stature, and combined therapy with recombinant human GH (rhGH) and GnRH analog (GnRHa) in pubertal patients has been suggested, but there are no data on final height.
The aim of the study was to analyze adult height after rhGH and GnRHa therapy in patients with SHOX haploinsufficiency.
Ten peripubertal patients with isolated SHOX defects participated in the study.
Five patients were followed without treatment, and five were treated with rhGH (50 mug/kg/d) and depot leuprolide acetate (3.75 mg/month).
Adult height sd score (SDS) was measured.
All patients followed without treatment had marked downward growth shift during puberty (height SDS, -1.2 +/- 0.7 at 11.4 +/- 1.4 yr; adult height SDS, -2.5 +/- 0.5). Conversely, four of five patients treated with rhGH for 2 to 4.9 yr associated to GnRHa for 1.4 to 5.8 yr improved their height SDS from -2.3 +/- 1.3 at 11.8 +/- 2.1 yr to a final height SDS of -1.7 +/- 1.6. The difference between the mean height SDS at the first evaluation and final height SDS was statistically significant in nontreated vs. treated patients (mean height SDS change, -1.2 +/- 0.4 vs. 0.6 +/- 0.4, respectively; P <0.001).
A gain in adult height of patients with isolated SHOX defects treated with combined rhGH and GnRHa therapy was demonstrated for the first time, supporting this treatment for children with SHOX defects who have just started puberty to avoid the loss of growth potential observed in these patients during puberty.
孤立性 SHOX 缺陷是身材矮小最常见的单基因病因，已建议对青春期患者进行重组人生长激素（rhGH）和促性腺激素释放激素类似物（GnRHa）联合治疗，但尚无最终身高的数据。
本研究旨在分析 SHOX 单倍体不足患者接受 rhGH 和 GnRHa 治疗后的成年身高。
10 名患有孤立性 SHOX 缺陷的青春期前患者参与了这项研究。
5 名患者未接受治疗，5 名患者接受 rhGH（50 μg/kg/d）和 depot 亮丙瑞林（3.75 mg/月）治疗。
测量成年身高标准差评分（SDS）。
所有未接受治疗的患者在青春期均出现明显的生长下降（身高 SDS，-1.2 ± 0.7，在 11.4 ± 1.4 岁时；成年身高 SDS，-2.5 ± 0.5）。相反，5 名接受 rhGH 治疗 2 至 4.9 年并联合 GnRHa 治疗 1.4 至 5.8 年的患者中，有 4 名患者的身高 SDS 从 11.8 ± 2.1 岁时的-2.3 ± 1.3 改善到最终身高 SDS 的-1.7 ± 1.6。未治疗组与治疗组的平均身高 SDS 变化值差异具有统计学意义（平均身高 SDS 变化，-1.2 ± 0.4 对 0.6 ± 0.4；P <0.001）。
首次证明了接受 rhGH 和 GnRHa 联合治疗的孤立性 SHOX 缺陷患者的成年身高有所增加，支持对刚刚进入青春期的 SHOX 缺陷儿童进行这种治疗，以避免这些患者在青春期期间出现的生长潜能丧失。
