促性腺激素释放激素类似物治疗下丘脑错构瘤导致性早熟5例临床分析

doi:10.3969/j.issn.1004-583X.2024.01.009

摘要/Abstract

摘要：

目的探讨儿童下丘脑错构瘤导致性早熟的临床特点和诊疗方案。方法回顾性分析2017年5月至2021年5月广州医科大学附属妇女儿童医疗中心诊治的下丘脑错构瘤导致性早熟患儿5例。在万方数据库及PubMed数据库中检索相关文献,总结下丘脑错构瘤导致性早熟的诊治特点。结果 5例患儿初诊年龄为6月~8岁。均以性早熟为突出表现。使用促性腺激素释放激素类似物(醋酸亮丙瑞林注射液或醋酸曲普瑞林注射液)治疗。性发育均获得明显控制。5例患儿性激素水平均明显下降,骨龄均获得明显的控制。病例1月经消失,乳腺从B2期减小到B1期。病例2和病例5阴茎和睾丸没有进一步增大。病例3和病例4乳腺从B3期减小到B2期。结论部分下丘脑错构瘤患儿主要临床表现为性早熟。若未合并癫痫等神经系统表现,可首先使用促性腺激素释放激素类似物治疗,效果良好,性早熟可得到明显控制,避免手术。

关键词: 错构瘤, 下丘脑, 促性腺激素释放激素类似物, 性早熟

Abstract:

Objective To investigate the clinical characteristics, diagnosis and treatment of precocious puberty caused by hypothalamic hamartomas in children. Methods Five cases of precocious puberty caused by hypothalamic hamartomas diagnosed and treated by Guangzhou Women and Children's Medical Center from May 2017 to May 2021 were analyzed retrospectively. Relevant literatures were searched in Wanfang and PubMed databases to summarize the diagnosis and treatment characteristics of precocious puberty caused by hypothalamic hamartomas. Results Five children with hypothalamic hamartomas were initially diagnosed from 6 months to 8 years old. Precocious puberty was the prominent performance. They were treated with gonadotropin releasing hormone analogues (GnRHa) (Enantone injection or Diphereline injection), achieving a significant outcome of controlled sexual development, including significantly decreased sex hormone levels and controlled bone age. The menstruation of Case 1 disappeared, and the breast development of stage B2 was recovered to stage B1. The penis and testicles of Case 2 and Case 5 did not further enlarge. The breast development of Case 3 and Case 4 was recovered from stage B3 to stage B2. Conclusion Precocious puberty is the main manifestation of hypothalamic hamartomas. GnRHa can be initially applied to those without neurological manifestations like epilepsy. They have an acceptable efficacy on controlling precocious puberty, so as to avoid a surgical treatment.

Key words: hamartoma, hypothalamus, gonadotropin releasing hormone analogue, precocious puberty

中图分类号:

R730.261

伊鹏, 李翠玲, 黄新疆, 曾春华. 促性腺激素释放激素类似物治疗下丘脑错构瘤导致性早熟5例临床分析[J]. 临床荟萃, 2024, 39(1): 53-56.

Yi Peng, Li Cuiling, Huang Xinjiang, Zeng Chunhua. Clinical analysis of 5 cases with precocious puberty caused by hypothalamic hamartomas treated with gonadotropin releasing hormone analogues[J]. Clinical Focus, 2024, 39(1): 53-56.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.01.009

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I1/53

图/表 5

表1 患儿一般资料

Tab.1 General information of pediatric patients

病例	性别	身高 (cm)	体重 (kg)	初诊年龄	主要症状	主要体征	初诊骨龄	头颅MRI检查
1	女	73.0	8.3	6月	阴道出血3天	右侧乳腺B2期,无阴毛	2岁	下丘脑灰结节区占位,大小约0.9 cm×0.9 cm×0.7 cm
2	男	105.4	19.0	3岁	阴茎增大3年,阴毛生长1个月	睾丸4 ml,阴茎4 cm, 阴毛P2期	7岁	鞍上灰结节乳头体及脚间窝区见一圆形结节影,大小约1.41 cm×1.16 cm
3	女	85.0	12.8	1岁8月	乳腺发育1个月	双侧乳腺B3期,无阴毛	2岁	下丘脑灰结节区占位,大小约1.2 cm×1.0 cm
4	女	84.0	12.8	1岁9月	乳腺发育2个月	双侧乳腺B3期,无阴毛	3岁	鞍上灰结节区占位,大小约0.5 cm×0.5 cm
5	男	142.4	34.0	8岁	阴毛生长3个月	睾丸8 ml,阴茎5 cm, 阴毛P3期	13岁	鞍上灰结节区占位,大小约1.4 cm×1.8 cm×1.9 cm

表2 GnRHa激发试验

Tab.2 GnRHa stimulation test

病例	FSH(IU/L)/LH(IU/L)
病例	0 min	30 min	60 min	90 min	120 min
1	5.03/52.67	25.48/63.33	29.36/57.78	30.13/51.93	28.95/40.50
2	1.75/2.53	3.51/13.49	2.94/13.39	3.90/13.88	3.80/12.95
3	4.91/2.66	23.11/66.23	28.22/58.54	27.86/51.69	25.8/42.81
4	4.56/2.70	19.40/69.63	23.70/69.49	25.59/57.95	23.49/43.32
5	1.04/1.10	2.03/12.29	2.29/18.76	2.95/20.34	3.08/19.78

表3 简易GnRHa激发试验

Tab.3 Simplified GnRHa stimulation test

病例	FSH(IU/L)/LH(IU/L)
病例	0 min	60 min
1	0.30/1.76	0.30/3.51
2	0.30/0.08	0.30/1.43
3	2.57/1.10	5.19/4.42
4	0.47/0.74	0.45/1.13
5	0.46/0.35	0.30/1.68

表4 治疗药物效果评价

Tab.4 Evaluation of therapeutic drugs

病例	治疗时间	治疗药物	维持剂量 100μg/kg	性激素FSH, LH变化	骨龄增长/年龄增长(岁)	性腺发育超声评估	性征改变	身高增长 (cm)
1	2017年05月-2021年05月,共46针	醋酸曲普瑞林注射液	1.35 mg	下降	4.0/5.0	卵巢减小	月经消失,乳腺减小到 B1期	28.9
2	2017年05月-2021年04月, 共42针	醋酸曲普瑞林注射液	2.00 mg	下降	2.0/4.9	睾丸没有继续增大	阴茎没有继续增大	18.5
3	2019年05月-2021年04月, 共23针	醋酸亮丙瑞林注射液	1.60 mg	下降	2.0/1.9	卵巢减小	乳腺减小到B2期	27.0
4	2020年05月-2021年05月, 共13针	醋酸曲普瑞林注射液	2.00 mg	下降	1.0/1.0	卵巢减小	乳腺减小到B2期	6.7
5	2019年03月-2021年07月, 共30针	醋酸曲普瑞林注射液	3.75 mg	下降	0/2.3	睾丸没有继续增大	阴茎没有继续增大	12.0

表1 FSH和LH治疗前后比较( x -±s, IU/L)

Tab.1 Comparison of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and after treatment ( x -±s, IU/L)

分组	例数	治疗前	治疗后	$t$ 值	$P$ 值
FSH 0 min	5	3.46±1.91	0.82±0.98	3.375	0.028
FSH 60 min	5	17.30±13.58	1.31±2.17	2.811	0.048
LH 0 min	5	12.33±22.56	0.81±0.66	1.170	0.307
LH 60 min	5	43.59±25.61	2.43±1.45	3.672	0.021

表1 FSH和LH治疗前后比较( x -±s, IU/L)

Tab.1 Comparison of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and after treatment ( x -±s, IU/L)

分组	例数	治疗前	治疗后	$t$ 值	$P$ 值
FSH 0 min	5	3.46±1.91	0.82±0.98	3.375	0.028
FSH 60 min	5	17.30±13.58	1.31±2.17	2.811	0.048
LH 0 min	5	12.33±22.56	0.81±0.66	1.170	0.307
LH 60 min	5	43.59±25.61	2.43±1.45	3.672	0.021

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