患有 SHOX 单倍剂量不足症患者的成人身高：一项真实世界的单中心研究。

Adult Height of Patients with SHOX Haploinsufficiency with or without GH Therapy: A Real-World Single-Center Study.

机构信息

Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

出版信息

Horm Res Paediatr. 2022;95(3):264-274. doi: 10.1159/000524374. Epub 2022 Apr 7.

DOI:10.1159/000524374

PMID:35390795

Abstract

INTRODUCTION

Isolated SHOX haploinsufficiency is a common monogenic cause of short stature. Few studies compare untreated and rhGH-treated patients up to adult height (AH). Our study highlights a growth pattern from childhood to AH in patients with SHOX haploinsufficiency and analyzes the real-world effectiveness of rhGH alone or plus GnRH analog (GnRHa).

METHODS

Forty-seven patients (18 untreated and 29 rhGH-treated) with SHOX haploinsufficiency were included in a longitudinal retrospective study. Adult height was attained in 13 untreated and 18 rhGH-treated (rhGH alone [n = 8] or plus GnRHa [n = 10]) patients.

RESULTS

The untreated group decreased height SDS from baseline to AH (-0.8 [-1.1; -0.4]), with an increase in the prevalence of short stature from 31% to 77%. Conversely, the rhGH-treated group had an improvement in height SDS from baseline to AH (0.6 [0.2; 0.6]; p < 0.001), with a reduction in the prevalence of short stature (from 61% to 28%). AH in the rhGH-treated patients was 1 SD (6.3 cm) taller than in untreated ones. Regarding the use of GnRHa, the subgroups (rhGH alone or plus GnRHa) attained similar AH, despite the higher prevalence of pubertal patients and worse AH prediction at the start of rhGH treatment in patients who used combined therapy.

CONCLUSION

The use of rhGH treatment improves AH in patients with SHOX haploinsufficiency, preventing the loss of height potential during puberty. In peripubertal patients, the addition of GnRHa to rhGH allows AH attainment similar to the AH of patients who start rhGH alone in the prepubertal age.

摘要

简介

孤立性 SHOX 杂合性不足是身材矮小的常见单基因病因。很少有研究比较未经治疗和 rhGH 治疗的患者直至成年身高（AH）。我们的研究强调了 SHOX 杂合性不足患者从儿童期到 AH 的生长模式，并分析了 rhGH 单独或加用 GnRH 类似物（GnRHa）的真实世界疗效。

方法

47 例 SHOX 杂合性不足患者（未经治疗 18 例，rhGH 治疗 29 例）纳入一项回顾性纵向研究。13 例未经治疗（n = 13）和 18 例 rhGH 治疗（rhGH 单独治疗 [n = 8] 或加用 GnRHa [n = 10]）患者达到 AH。

结果

未经治疗组从基线到 AH 的身高 SDS 下降（-0.8 [-1.1; -0.4]），矮小症的患病率从 31%增加到 77%。相反，rhGH 治疗组从基线到 AH 的身高 SDS 改善（0.6 [0.2; 0.6]；p < 0.001），矮小症的患病率降低（从 61%降至 28%）。rhGH 治疗患者的 AH 比未经治疗患者高 1 个标准差（6.3 厘米）。关于 GnRHa 的使用，rhGH 单独治疗或加用 GnRHa 的亚组（rhGH 单独治疗或加用 GnRHa）获得了相似的 AH，尽管联合治疗患者开始 rhGH 治疗时青春期患者的比例较高，且预测 AH 较差。