Please wait a minute...
J Zhejiang Univ (Med Sci)
    
Efficacy and safety of letrozole in treatment of McCune-Albright Syndrome girls with peripheral precocious puberty
XU De, LU Wenli, WANG Xueqing, WANG Junqi, XIE Yiwen, DONG Zhiya, WANG Wei
Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Download: HTML (   PDF(375KB)
Export: BibTeX | EndNote (RIS)      

Abstract  Objective: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. Methods: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of LH and FSH; and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2mg/m2·d for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. Results: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 (P=0.005); the predicted adult height (PAH) increased from 156.18 ±5.86 cm to 157.4 ±2. 06 cm after treatment (P=0.023), the E2 level decreased significantly, while the teststosterone (T) level did not increase significantly and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion occurred. Conclusion: Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.

Key wordsPuberty, precocious      McCune-Albright syndrome      Aromatase inhibitors      Letrozole      Girls     
Received: 05 December 2019      Published: 29 May 2020
CLC:  R588  
  R725.8  
Cite this article:

XU De, LU Wenli, WANG Xueqing, WANG Junqi, XIE Yiwen, DONG Zhiya, WANG Wei. Efficacy and safety of letrozole in treatment of McCune-Albright Syndrome girls with peripheral precocious puberty. J Zhejiang Univ (Med Sci), 0, 0(0): 3-0.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.04.03     OR     http://www.zjujournals.com/med/Y0/V0/I0/3


芳香化酶抑制剂治疗纤维性骨营养不良综合征女童外周性性早熟疗效观察

目的:探讨应用第三代芳香化酶抑制剂来曲唑治疗纤维性骨营养不良综合征(MAS)女童外周性性早熟的疗效及安全性。方法:选取2012年3月至2017年6月上海交通大学医学院附属瑞金医院儿科的MAS女童21例。患儿反复阴道出血、乳房增大同时伴或不伴牛奶咖啡斑或骨纤维发育不良,LH和FSH水平低下,排除先天性肾上腺皮质增生症、分泌雌激素的肿瘤及外源性雌激素摄入所致等情况。给予来曲唑0.5~2 mg·(m2·d)治疗,疗程6~12个月,观察患儿乳房分期变化、阴道出血次数、性激素水平、肝功能及骨龄变化及子宫卵巢容积变化及有无不良事件发生。结果:经过来曲唑治疗后,患儿骨龄/实际年龄放缓(1.23±0.30降至1.11±0.18,P<0.01);患儿预测成人身高从治疗前的(156.2±5.9)cm增加至治疗后的(158.4±2.1)cm(P<0.05);患儿阴道出血次数明显减少,雌二醇水平下降,睾酮未见明显升高;治疗后患儿子宫未见明显增大,也未发生卵巢扭转及肝酶升高等不良反应。结论:儿童MAS的内分泌表现以性早熟最为多见,第三代芳香化酶抑制剂来曲唑治疗MAS相关的外周性性早熟可延缓骨龄进展,减少阴道出血的频率,也未出现肝酶升高等肝功能受损的不良反应。

关键词: 青春期,早熟,  纤维性骨营养不良综合征,  芳香化酶抑制剂,  来曲唑,  女童 
[1] DUMITRESCU C E, COLLINS M T. McCune-Albright syndrome[J]. Orphanet J Rare Dis, 2008, 3(1). DOI:10.1186/1750-1172-3-12.
[2] HOLBROOK L, BRADY R. McCune-Albright syndrome[J]. StatPearls, 2019.
[3] LIETMAN S A, SCHWINDINGER W F, LEVINE M A. Genetic and molecular aspects of McCune-Albright syndrome[J]. Pediatr Endocrinol Rev, 2007,4 Suppl 4:380-385.
[4] DE G BUFF PASSONE C, KUPERMAN H, CABRAL DE MENEZES-FILHO H, et al. Tamoxifen improves final height prediction in girls with mccune-albright syndrome:a long follow-up[J]. Horm Res Paediatr, 2015,84(3):184-189. DOI:10.1159/000435881.
[5] EUGSTER E A, RUBIN S D, REITER E O, et al. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome:a multicenter trial[J]. J Pediatr, 2003,143(1):60-66. DOI:10.1016/S0022-3476(03)00128-8.
[6] CHEN M, EUGSTER E A. Central precocious puberty:update on diagnosis and treatment[J]. Paediatr Drugs, 2015,17(4):273-281. DOI:10.1007/s40272-015-0130-8.
[7] FEUILLAN P, CALIS K, HILL S, et al. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome:a pilot study[J]. J Clin Endocrinol Metab, 2007,92(6):2100-2106. DOI:10.1210/jc.2006-2350.
[8] ESTRADA A, BOYCE A M, BRILLANTE B A, et al. Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome[J]. Eur J Endocrinol, 2016,175(5):477-483. DOI:10.1530/EJE-16-0526.
[9] ZHU G, YE X, DONG Z, et al. Highly sensitive droplet digital PCR method for detection of EGFR-activating mutations in plasma cell-free DNA from patients with advanced non-small cell lung cancer[J]. J Mol Diagn, 2015,17(3):265-272. DOI:10.1016/j.jmoldx.2015.01.004.
[10] NARUMI S, MATSUO K, ISHII T, et al. Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing[J/OL]. PLoS One, 2013,8(3):e60525. DOI:10.1371/journal.pone.0060525.
[11] 秦雪艳, 陆文丽, 王俊祺,等. 41例McCune-Albright综合征女童临床及基因分析[J].中华内分泌代谢杂志, 2016, 32(12):995-998. DOI:10.3760/cma.j.issn.1000-6699.2016.12.004. QIN Xueyan, LU Wenli, WANG Junqi, et al. Analysis of clinical features and related genes variation in 41 girls with McCune-Albright syndrome[J]. Chinese Journal of Endocrinology and Metabolism,2016, 32(12):995-998. DOI:10.3760/cma.j.issn.1000-6699.2016.12.004. (in Chinese)
[12] 梁雁,罗小平.进一步规范中枢性性早熟的诊疗[J].中华儿科杂志,2015,53(6):405-408. DOI:10.3760/cma.j.issn.0578-1310.2015.06.002. LIANG Yan, LUO Xiaoping. Further standardize the diagnosis and treatment of central precocious puberty[J]. Chinese Journal of Pediatrics,2015,53(6):405-408. DOI:10.3760/cma.j.issn.0578-1310.2015.06.002. (in Chinese)
[13] 李辉,季成叶,宗心南, 等.中国0~18岁儿童、青少年身高、体重的标准化生长曲线[J].中华儿科杂志,2009,47(7):487-492. DOI:10.3760/cma.j.issn.0578-1310.2009.07.003. LI Hui, JI Chengye, ZONG Xinnan, et al. Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years[J]. Chinese Journal of Pediatrics, 2009,47(7):487-492. DOI:10.3760/cma.j.issn.0578-1310.2009.07.003. (in Chinese)
[14] FEUILLAN P P, JONES J, CUTLER G B JR. Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome[J]. J Clin Endocrinol Metab, 1993,77(3):647-651. DOI:10.1210/jcem.77.3.8370686.
[15] FEUILLAN P P, FOSTER C M, PESCOVITZ O H, et al. Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone[J]. N Engl J Med, 1986,315(18):1115-1119. DOI:10.1056/NEJM198610303151802.
[16] WANG X, YU Q. Management of precocious puberty in girls with McCune-Albright syndrome using letrozole[J]. Endocr Connect, 2018,7(12):1424-1431. DOI:10.1530/EC-18-0344.
[1] LI Yanhong, DU Minlian, MA Huamei, CHEN Qiuli, CHEN Hongshan, ZHANG Jun.. Efficacy of aromatase inhibitor in treatment of male adolescents with idiopathic short stature[J]. J Zhejiang Univ (Med Sci), 0, 0(0): 5-0.
[2] KONG Yuanmei, CHEN Hong, LIANG Li, ZHENG Maoni, FANG Yanlan, WANG Chunlin. Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature[J]. J Zhejiang Univ (Med Sci), 0, 0(0): 6-0.
[3] WANG Chunlin, LIANG Li. Reconsideration of the third-generation non-steroidal aromatase inhibitors in clinical pediatrics[J]. J Zhejiang Univ (Med Sci), 0, 0(0): 1-0.
[4] YU Bingqing, NIE Min, WU Xueyan, MAO Jiangfeng, WANG Xi, MA Wanlu, JI Wen, HUANG Qibin, ZHANG Rui. Efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development[J]. J Zhejiang Univ (Med Sci), 0, 0(0): 2-0.
[5] 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]. J Zhejiang Univ (Med Sci), 0, 0(0): 4-0.