Jorge Alexander A L, Edouard Thomas, Maghnie Mohamad, Pietropoli Alberto, Kelepouris Nicky, Romano Alicia, Zenker Martin, Horikawa Reiko
Unidade de Endocrinologia-Genetica, LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil.
Endocrine, Bone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, RESTORE INSERM UMR1301, Toulouse, France.
Endocr Connect. 2022 Apr 15;11(4):e210615. doi: 10.1530/EC-21-0615.
Mutations in PTPN11 are associated with Noonan syndrome (NS). Although the effectiveness of growth hormone therapy (GHT) in treating short stature due to NS has been previously demonstrated, the effect of PTPN11 mutation status on the long-term outcomes of GHT remains to be elucidated.
This analysis included pooled data from the observational American Norditropin Studies: Web-Enabled Research Program (NCT01009905) and the randomized, double-blinded GHLIQUID-4020 clinical trial (NCT01927861). Pediatric patients with clinically diagnosed NS and confirmed PTPN11mutation status were eligible for inclusion. The effectiveness analysis included patients who were GHT-naïve and pre-pubertal at GHT start. Growth outcomes and safety were assessed over 4 years of GHT (Norditropin®, Novo Nordisk A/S).
A total of 69 patients were included in the effectiveness analysis (71% PTPN11 positive). The proportion of females was 32.7 and 30.0% in PTPN11-positive and negative patients, respectively, and mean age at GHT start was 6.4 years in both groups. Using general population reference data, after 4 years of GHT, the mean (s.d.) height SD score (HSDS) was -1.9 (1.1) and -1.7 (0.8) for PTPN11-positive and PTPN11-negative patients, respectively, with no statistical difference observed between groups. The mean (s.d.) change in HSDS at 4 years was +1.3 (0.8) in PTPN11-positive patients and +1.5 (0.7) in PTPN11-negative patients (no significant differences between groups). Safety findings were consistent with previous analyses.
GHT resulted in improved growth outcomes over 4 years in GHT-naïve, pre-pubertal NS patients, irrespective of PTPN11 mutation status.
PTPN11基因的突变与努南综合征（NS）相关。尽管生长激素治疗（GHT）对NS所致身材矮小的有效性此前已得到证实，但PTPN11突变状态对GHT长期疗效的影响仍有待阐明。
本分析纳入了来自观察性美国诺德生长激素研究：网络研究项目（NCT01009905）和随机双盲GHLIQUID - 4020临床试验（NCT01927861）的汇总数据。临床诊断为NS且PTPN11突变状态得到确认的儿科患者符合纳入标准。有效性分析纳入了开始接受GHT时未接受过GHT治疗且未进入青春期的患者。在4年的GHT治疗期间（使用诺德生长激素®，诺和诺德公司）评估生长结局和安全性。
有效性分析共纳入69例患者（71%为PTPN11阳性）。PTPN11阳性和阴性患者中女性比例分别为32.7%和30.0%，两组开始接受GHT治疗时的平均年龄均为6.4岁。使用一般人群参考数据，GHT治疗4年后，PTPN11阳性和阴性患者的平均（标准差）身高标准差评分（HSDS）分别为 - 1.9（1.1）和 - 1.7（0.8），两组间未观察到统计学差异。PTPN11阳性患者4年时HSDS的平均（标准差）变化为 + 1.3（0.8），PTPN11阴性患者为 + 1.5（0.7）（两组间无显著差异）。安全性结果与先前分析一致。
对于未接受过GHT治疗、未进入青春期的NS患者，无论PTPN11突变状态如何，GHT在4年期间均能改善生长结局。
