生长激素联合手术治疗中度OSA合并特发性身材矮小症患儿的有效性和安全性

doi:10.3969/j.issn.1674-8115.2026.02.009

摘要/Abstract

摘要：

目的·探讨常规治疗、单纯重组人生长激素（recombinant human growth hormone，rhGH）治疗以及腺样体扁桃体手术联合rhGH治疗对中度阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）合并特发性身材矮小症（idiopathic short stature，ISS）患儿的临床疗效和安全性。方法·纳入2020—2023年就诊于上海交通大学医学院附属儿童医院耳鼻咽喉头颈外科和内分泌科的中度OSA合并ISS患儿共60例。根据不同的临床治疗方案将患儿分为3组（常规治疗组、单纯rhGH治疗组和手术联合rhGH治疗组），每组20例。分析治疗前后3组患儿生长效应指标［包括身高、身高增幅、骨龄、骨龄成熟度、胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）水平和胰岛素样生长因子结合蛋白-3（IGF-binding protein-3，IGFBP-3）水平等］动态变化、临床症状及疗效［阻塞性呼吸暂停低通气指数（obstructive apnea hypopnea index，OAHI）、最低外周血氧饱和度和儿童阻塞性睡眠呼吸暂停特异性生活质量调查表（Disease Specific Quality of Life for Children with Obstructive Sleep Apnea-18 Items Survey，OSA-18）评分］。结果·治疗后6、12个月，在身高增幅和生长激素分泌（IGF-1、IGFBP-3水平）方面，单纯rhGH治疗组患儿的改善优于常规治疗组，手术联合rhGH治疗组优于单纯rhGH治疗组，差异均具有统计学意义（均P<0.05）。经过12个月治疗，3组患儿身高和骨龄与治疗前相比均有所增长（均P<0.001），均未出现血脂、代谢等相关异常反应。手术联合rhGH治疗组患儿的骨龄成熟度与治疗前相比差异有统计学意义（P=0.002），而单纯rhGH治疗组和对照组的骨龄成熟度与治疗前比较差异无统计学意义。与治疗前相比，单纯rhGH治疗组和手术联合rhGH治疗组患儿IGF-1和IGFBP-3水平均有提升（均P<0.001）；而对照组与治疗前相比差异无统计学意义。与治疗前相比，手术联合rhGH治疗组患儿OAHI和OSA-18评分降低，最低外周血氧饱和度提升，差异均具有统计学意义（均P<0.001）；而对照组和单纯rhGH治疗组患儿该3项指标与治疗前相比差异无统计学意义。此时，手术联合rhGH治疗组有16人达到身高标准化生长曲线（同年龄、同性别正常儿童身高均值±1个标准差），单纯rhGH治疗组有2人达到，对照组无人达到；手术联合rhGH治疗组与单纯rhGH治疗组相比、单纯rhGH治疗组与对照组相比，差异均具有统计学意义（均P<0.001）。结论·对于中度OSA合并ISS儿童而言，rhGH治疗在代谢安全性方面总体可控，且腺样体扁桃体手术联合rhGH治疗对促进患儿身高增长具有显著的协同效应。

关键词: 阻塞性睡眠呼吸暂停, 生长激素, 特发性身材矮小症, 生长发育, 间歇性缺氧

Abstract:

Objective ·To compare the clinical efficiency and safety of conventional treatment, recombinant human growth hormone (rhGH) monotherapy, and adenotonsillectomy combined with rhGH in children with moderate obstructive sleep apnea (OSA) and idiopathic short stature (ISS). Methods ·A total of 60 children with moderate OSA and ISS were enrolled between 2020 and 2023 in the Department of Otolaryngology Head and Neck Surgery and the Department of Endocrinology at Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine. Based on different clinical treatment regimens, the children were divided into three groups (conventional treatment group, rhGH treatment group, and adenotonsillectomy combined with rhGH treatment group), with 20 cases in each group. The dynamic changes in growth-related indicators [including height, height increase, bone age, bone age maturity, insulin-like growth factor-1 (IGF-1) level, and insulin-like growth factor-binding protein-3 (IGFBP-3) level] were analyzed among the three groups before and after treatment. In addition, clinical symptoms and therapeutic efficacy in three groups were evaluated before treatment and at 6 and 12 months post-treatment, including the obstructive apnea-hypopnea index (OAHI), minimum peripheral oxygen saturation, and Disease-Specific Quality of Life for Children with Obstructive Sleep Apnea-18 Items Survey (OSA-18). Results ·At 6 and 12 months post-treatment, the children in the rhGH treatment group showed superior improvements in height increase and growth hormone secretion (IGF-1 and IGFBP-3 levels) compared with those in the conventional treatment group. The surgery combined with rhGH treatment group also demonstrated better outcomes than the rhGH treatment group, with the differences being statistically significant (all P<0.05). After 12 months of treatment, height and bone age of the three groups of children increased compared with pre-treatment (all P<0.001), and no abnormalities in blood lipid levels or metabolism were observed. The bone age maturity of children in the surgery combined with rhGH treatment group showed a statistically significant difference compared with pre-treatment (P=0.002). In contrast, no statistically significant difference was observed in bone age maturity between the rhGH treatment group and the control group. Compared with pre-treatment levels, both the rhGH treatment group and the surgery combined with rhGH treatment group showed significant increases in IGF-1 and IGFBP-3 levels (both P<0.001); however, no statistically significant differences were observed in the control group compared with pre-treatment levels. Compared with pre-treatment levels, the OAHI and OSA-18 scores in the surgery combined with rhGH treatment group were significantly reduced, and the minimum peripheral oxygen saturation was improved, with all differences being statistically significant (all P<0.001). In contrast, no statistically significant differences were observed in these three indicators of the control group and the rhGH treatment group compared with pre-treatment levels. At 12 months, 16 children in the surgery combined with rhGH treatment group reached the standardized height growth curve (mean height of normal children of the same age and sex ±1 standard deviation), whereas only 2 children in the rhGH treatment group met this criterion. No child in the control group achieved this outcome. The differences between the surgery combined with rhGH treatment group and the rhGH treatment group, as well as between the rhGH treatment group and the control group, were statistically significant (all P<0.001). Conclusion ·In children with moderate OSA and ISS, rhGH therapy demonstrates generally acceptable metabolic safety, and adenoid-tonsillectomy combined with rhGH treatment shows significant synergistic effects in promoting height growth.

Key words: obstructive sleep apnea (OSA), growth hormone (GH), idiopathic short stature (ISS), growth and development, intermittent hypoxia

中图分类号:

R766.3

陈芳, 周莎莎, 李嫔. 生长激素联合手术治疗中度OSA合并特发性身材矮小症患儿的有效性和安全性[J]. 上海交通大学学报（医学版）, 2026, 46(2): 206-212.

Chen Fang, Zhou Shasha, Li Pin. Efficiency and safety of growth hormone combined with surgery in the treatment of children with moderate OSA and idiopathic short stature[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(2): 206-212.

图/表 3

参考文献 19

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Indicator	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P value
Male/n(%)	10 (50.0)	10 (50.0)	11 (55.0)	0.935
Age/year	6.03±0.70	6.05±0.67	6.05±0.71	0.991
Degree of adenoid hypertrophy/n(%)				0.982
Ⅱ	11 (55.0)	12 (60.0)	11 (55.0)
Ⅲ	5 (25.0)	3 (15.0)	4 (20.0)
Ⅳ	4 (20.0)	5 (25.0)	5 (25.0)
Snoring history/year	2.93±0.98	3.08±1.00	2.85±0.81	0.742
Bone age/year	4.94±0.48	5.10±0.61	5.02±0.80	0.720
Height/cm	106.66±3.71	106.48±4.16	106.24±3.84	0.945
HtSDS	-2.24±0.19	-2.33±0.24	-2.38±0.13	0.085
Bone age maturation	0.82±0.08	0.85±0.09	0.83±0.09	0.713

Indicator	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P value
Male/n(%)	10 (50.0)	10 (50.0)	11 (55.0)	0.935
Age/year	6.03±0.70	6.05±0.67	6.05±0.71	0.991
Degree of adenoid hypertrophy/n(%)				0.982
Ⅱ	11 (55.0)	12 (60.0)	11 (55.0)
Ⅲ	5 (25.0)	3 (15.0)	4 (20.0)
Ⅳ	4 (20.0)	5 (25.0)	5 (25.0)
Snoring history/year	2.93±0.98	3.08±1.00	2.85±0.81	0.742
Bone age/year	4.94±0.48	5.10±0.61	5.02±0.80	0.720
Height/cm	106.66±3.71	106.48±4.16	106.24±3.84	0.945
HtSDS	-2.24±0.19	-2.33±0.24	-2.38±0.13	0.085
Bone age maturation	0.82±0.08	0.85±0.09	0.83±0.09	0.713

Indicator	At 6 months post-treatment					At 12 months post-treatment
Indicator	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P₁ value	P₂ value	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P₁ value	P₂value
Height/cm	109.70±4.03	111.56±4.25	114.31±3.91	0.304	0.100	112.11±4.04	116.55±4.52	120.02±4.26	0.005	0.034
ΔHeight/cm	3.04±0.66	5.14±0.67	8.07±0.84	<0.001	<0.001	5.46±0.85	10.08±1.25	13.78±1.33	<0.001	<0.001
HtSDS	‒	‒	‒	‒	‒	-2.22±0.22	-1.38±0.34	-0.70±0.30	<0.001	<0.001
Subject within standard growth curve for height/n(%)	‒	‒	‒	‒	‒	0 (0)	2 (10.00)	16 (80.00)	<0.001	<0.001
Bone age/year	‒	‒	‒	‒	‒	5.62±0.45	6.24±0.61	6.48±0.82	0.009	0.473
Bone age maturation	‒	‒	‒	‒	‒	0.80±0.07	0.89±0.06	0.92±0.08	0.001	0.315
IGF-1/(ng·mL^-1)	91.75±19.54	205.00±46.31	281.55±98.69	<0.001	0.001	91.10±18.50	251.15±58.88	298.35±85.39	<0.001	0.045
IGFBP-3/(μg·mL^-1)	3.18±0.47	4.11±0.71	5.37±1.06	0.001	<0.001	3.16±0.50	4.73±0.95	5.71±1.03	<0.001	0.002

Indicator	At 6 months post-treatment					At 12 months post-treatment
Indicator	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P₁ value	P₂ value	Control group (n=20)	rhGH treatment group (n=20)	Surgery combined with rhGH treatment group (n=20)	P₁ value	P₂value
Height/cm	109.70±4.03	111.56±4.25	114.31±3.91	0.304	0.100	112.11±4.04	116.55±4.52	120.02±4.26	0.005	0.034
ΔHeight/cm	3.04±0.66	5.14±0.67	8.07±0.84	<0.001	<0.001	5.46±0.85	10.08±1.25	13.78±1.33	<0.001	<0.001
HtSDS	‒	‒	‒	‒	‒	-2.22±0.22	-1.38±0.34	-0.70±0.30	<0.001	<0.001
Subject within standard growth curve for height/n(%)	‒	‒	‒	‒	‒	0 (0)	2 (10.00)	16 (80.00)	<0.001	<0.001
Bone age/year	‒	‒	‒	‒	‒	5.62±0.45	6.24±0.61	6.48±0.82	0.009	0.473
Bone age maturation	‒	‒	‒	‒	‒	0.80±0.07	0.89±0.06	0.92±0.08	0.001	0.315
IGF-1/(ng·mL^-1)	91.75±19.54	205.00±46.31	281.55±98.69	<0.001	0.001	91.10±18.50	251.15±58.88	298.35±85.39	<0.001	0.045
IGFBP-3/(μg·mL^-1)	3.18±0.47	4.11±0.71	5.37±1.06	0.001	<0.001	3.16±0.50	4.73±0.95	5.71±1.03	<0.001	0.002

Item	Control group			rhGH treatment group			Surgery combined with rhGH treatment group
Item	Before treatment	12-month after treatment	P value	Before treatment	12-month after treatment	P value	Before treatment	12-month after treatment	P value
Height/cm	106.66±3.71	112.11±4.04	<0.001	106.48±4.16	116.55±4.52	<0.001	106.24±3.84	120.02±4.26	<0.001
HtSDS	-2.24±0.19	-2.22±0.22	0.731	-2.33±0.24	-1.38±0.34	<0.001	-2.38±0.13	-0.70±0.30	<0.001
Bone age/year	4.94±0.48	5.62±0.45	<0.001	5.10±0.61	6.24±0.61	<0.001	5.02±0.80	6.48±0.82	<0.001
Bone age maturation	0.82±0.08	0.80±0.07	0.384	0.85±0.09	0.89±0.06	0.112	0.83±0.09	0.92±0.08	0.002
IGF-1/(ng·mL^-1)	91.32±19.90	91.10±18.50	0.972	81.55±31.25	251.15±58.88	<0.001	97.51±32.99	298.35±85.39	<0.001
IGFBP-3/(μg·mL^-1)	3.06±0.43	3.16±0.50	0.466	3.27±0.70	4.73±0.95	<0.001	3.59±0.94	5.71±1.03	<0.001
OAHI/(event·h^-1)	6.65±0.93	6.40±0.99	0.172	6.30±0.80	5.95±0.82	0.069	7.41±1.04	0.21±0.41	<0.001
Minimum SpO₂/%	80.55±1.90	80.30±01.82	0.501	80.90±0.91	81.25±1.11	0.110	80.30±1.52	93.75±1.06	<0.001
OSA-18/score	65.25±4.86	63.95±6.32	0.112	65.95±4.44	64.95±6.51	0.202	66.50±3.77	22.20±2.48	<0.001