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浙江大学学报（医学版）
浙江大学学报（医学版）  2020, Vol. 49 Issue (3): 302-307    DOI: 10.3785/j.issn.1008-9292.2020.04.04
专题报道：芳香化酶抑制剂的临床应用     
来曲唑对21-羟化酶缺乏型先天性肾上腺皮质增生症患儿生长发育的影响
王倩1(),张书乐2,马雪2,李桂梅1,*(),王增敏1,王凤雪1
1. 山东第一医科大学附属省立医院小儿内分泌综合科, 山东 济南 250014
2. 山东大学附属省立医院小儿内分泌综合科, 山东 济南 250014
Efficacy of letrozole in treatment of children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency
WANG Qian1(),ZHANG Shule2,MA Xue2,LI Guimei1,*(),WANG Zengmin1,WANG Fengxue1
1. Department of Pediatric Endocrine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250014, China
2. Department of Pediatric Endocrine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250014, China
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摘要：

目的: 探讨来曲唑联合常规方法治疗21-羟化酶缺乏型先天性肾上腺皮质增生症（CAH）患儿的可行性。方法: 选取2010年12月至2016年1月确诊的4~10岁21-羟化酶缺乏型CAH患儿共28例，其中男性19例，女性9例。入组患儿前6个月为常规治疗（氢化可的松、氟氢可的松），第6个月末开始加用来曲唑联合治疗。通过自身前后对照的方法，对联合治疗前后患儿的骨龄进展速度、预期成年身高、性征发育程度及性激素水平、可能的不良反应等指标进行统计。结果: 加用来曲唑联合治疗后，患儿身高增长速度在短期（6个月内）有所下降，但很快恢复正常；联合治疗12个月后患儿骨龄别身高标准差分值（HtSDSBA）较入组时及常规治疗均显著改善（P < 0.05或P < 0.01）；骨龄与时序年龄差值在联合治疗18个月后较常规治疗显著改善（P < 0.05）；女性患儿预期成年身高在联合治疗12个月后较常规治疗显著改善（P < 0.05），男性患儿在联合治疗18个月后预期成年身高亦显著改善（P < 0.05）；患儿卵泡刺激素、促黄体生成素升高，但未达到中枢性性早熟标准；患儿雌二醇水平降低（P < 0.01）；患儿睾酮水平无显著改变。来曲唑联合治疗24个月，患儿未见多毛、严重痤疮、头疼、骨痛、肥胖、高血压、皮疹等不良反应。结论: 来曲唑联合常规治疗的方案可用于21-羟化酶缺乏型CAH患儿长期治疗，特别是骨龄明显超期、预期成年身高受损的患儿，可实现抑制骨龄进展、改善预期成年身高的治疗目的。
关键词： 肾上腺增生, 先天性;  21-羟化酶缺乏症;  儿童;  芳香酶抑制剂;  来曲唑;  治疗效果;  安全性;  肾上腺增生, 先天性;  21-羟化酶缺乏症;  儿童;  芳香酶抑制剂;  来曲唑;  治疗效果;  安全性    
Abstract:

Objective: To assess the efficacy of letrozole in treatment of children with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21-OHD). Methods: Twenty eight children, including 19 boys and 9 girls aged 4-10y, with CAH due to 21-OHD were enrolled in the study. At the first six months of study, all children received conventional treatment with hydrocortisone or fludrocortisone, then letrozole was added to original regimen. The height velocity (HV), difference between bone age and chronological age (BA-CA), height standard diviation score based on bone age (HtSDSBA), predicted adult height (PAH), Tanner phase, sex hormone, and possible adverse reaction were evaluated and compared between those before and after letrozole treatment. Results: After 6 months of letrozole treatment, there was significant deceleration of HV, but it would recover soon. There was significant increase of HtSDSBA after 12 months of letrozole treatment (P < 0.05 or P < 0.01), and significant changes in BA-CA after 18 months of letrozole treatment (P < 0.05). PAH of female children was significantly increased during letrozole treatment (P < 0.05), whereas PAH of male children was significantly increased 18 months after letrozole treatment (P < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased, but did not meet the diagnostic criteria of central precocious puberty. Estradiol was significantly decreased (P < 0.01), but no changes in testosterone level was observed. During 24 months letrozole treatment, no hirsutism, severe acne, headache, bone pain, obesity, hypertension, rash and other adverse reactions were observed. Conclusions: Letrozole can delay bone maturation and improve PAH, which can be used with conventional treatment for children with CAH due to 21-OHD, especially for those with high BA and low PAH.
Key words: Adrenal hyperplasia, congenital    21-hydroxylase deficiency    Child    Aromatase inhibitors    Letrozole    Treatment outcome    Safety    Adrenal hyperplasia, congenital    21-hydroxylase deficiency    Child    Aromatase inhibitors    Letrozole    Treatment outcome    Safety
收稿日期: 2019-12-04 出版日期: 2020-05-29
CLC:  R588  
通讯作者: 李桂梅     E-mail: wangqian8482752@163.com;liguimei2013@126.com
作者简介: 王倩(1984-), 女, 博士, 主治医师, 主要从事儿科内分泌疾病研究; E-mail:wangqian8482752@163.com; https://orcid.org/0000-0002-2166-8611|王倩(1984-), 女, 博士, 主治医师, 主要从事儿科内分泌疾病研究; E-mail:wangqian8482752@163.com; https://orcid.org/0000-0002-2166-8611
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王倩
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引用本文:

王倩,张书乐,马雪,李桂梅,王增敏,王凤雪. 来曲唑对21-羟化酶缺乏型先天性肾上腺皮质增生症患儿生长发育的影响[J]. 浙江大学学报（医学版）, 2020, 49(3): 302-307.

WANG Qian,ZHANG Shule,MA Xue,LI Guimei,WANG Zengmin,WANG Fengxue. Efficacy of letrozole in treatment of children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. J Zhejiang Univ (Med Sci), 2020, 49(3): 302-307.

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http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.04.04    或    http://www.zjujournals.com/med/CN/Y2020/V49/I3/302

治疗时间 n 身高增长速度(cm/年) 骨龄与时序年龄差值(岁) HtSDSBA 预期成年身高(cm)
男性 女性
*与常规治疗期末比较, P＜0.05；HtSDSBA：骨龄别身高标准差分值.
常规治疗期末 28 9.79±2.95 4.9±1.9 -3.62±1.23 146.2±9.1 131.4±10.1
联合治疗6个月 28 8.29±2.35* 4.9±1.8 -3.21±1.31 150.0±9.4 133.5±10.3
12个月 28 9.17±2.42 4.5±1.5 -2.75±1.03* 151.6±8.1 140.7±7.1*
18个月 26 8.55±2.42 4.1±1.8* -2.33±1.25* 155.6±10.3* 141.3±6.2*
24个月 26 9.32±1.60 4.2±1.6* -2.15±1.30* 157.2±10.4* 144.2±10.1*
表 1  不同治疗时间点患儿身高增长速度、骨龄及预期成年身高的变化
治疗期别 n 卵泡刺激素(U/L) 促黄体生成素(U/L) 雌二醇(pmol/L) 睾酮(nmol/L)
“—”：无相关数据.*3例患儿因Tanner分期进展退出联合治疗.
常规治疗期 19 0.57±0.27 0.15±0.09 68.60±44.59 0.56±0.10
联合治疗期* 16 2.16±1.34 0.33±0.11 28.45±14.09 0.52±0.15
t值 — -3.37 -1.61 3.43 0.20
P值 — ＜0.05 ＜0.05 ＜0.01 >0.05
表 2  联合治疗后男性患儿垂体-性腺轴激素变化
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