Wang Hongli,Xia Jipeng,Zhu Rongkun,et al.Complete androgen insensitivity syndrome:one case report with a literature review[J].Journal of Clinical Pediatric Surgery,2025,(03):271-277.[doi:10.3760/cma.j.cn101785-202409049-013]
完全性雄激素不敏感综合征1例及文献分析
- Title:
- Complete androgen insensitivity syndrome:one case report with a literature review
- Keywords:
- Androgen-Insensitivity Syndrome; Gonads; Surgical Procedures; Operative; Child
- 摘要:
- 目的 探讨儿童完全性雄激素不敏感综合征的临床特征、诊断及治疗策略。方法 回顾性分析2024年3月青岛大学附属医院小儿外科收治的1例完全性雄激素不敏感综合征患儿临床资料。以“complete androgen insensitivity syndrome”为检索词,检索PubMed数据库相关文献;以“完全性雄激素不敏感综合征”为检索词,检索中国知网、万方医学网相关文献;检索时间为2013年1月至2023年10月。收集本院及符合纳排标准文献中完全性雄激素不敏感综合征患儿的一般资料、临床表现、治疗方式及随访结果,并进行总结分析。结果 本院收治病例社会性别为女性,年龄13岁2个月,因原发性闭经入院。经临床症状及体征、体表肿物彩色多普勒超声、性激素检查、染色体核型分析确诊为完全性雄激素不敏感综合征,行“腹腔镜下双侧隐睾探查术+双侧睾丸切除术”。病理提示睾丸组织萎缩,曲细精管内未见生精细胞;术后康复出院。随访显示患儿双侧乳腺增生,性激素水平下降,截至目前该患儿一般情况良好。获得符合标准的文献10篇,共报道11例完全性雄激素不敏感综合征患儿,社会性别均为女性,诊断年龄26天至17岁,主要以原发性闭经、腹股沟斜疝就诊,患儿大多具有典型的女性外生殖器外观,7例阴道为盲端,1例阴道长度正常但狭窄;11例均行染色体核型分析,10例为46,XY,1例为47,XXY.ishYp11.3(SRY+);11例均行手术探查,其中1例将性腺重新定位在腹部,1例家属要求暂缓手术,其余9例行性腺切除术。术后随访发现,7例恢复良好(行激素替代治疗,最长随访时间20年),1例出现乳腺增生,3例失访。结论 完全性雄激素不敏感综合征是一种罕见疾病,常以原发性闭经就诊,在青春期之前常因腹股沟区肿物被误诊为腹股沟斜疝。当发现女孩腹股沟斜疝或原发性闭经时应考虑该疾病的可能,需通过进一步影像学检查和染色体核型分析进行鉴别诊断,必要时行基因检测以确诊。诊断完全性雄激素不敏感综合征后应进行手术治疗,手术时机尚存在争议,建议青春期后或成年早期手术切除性腺以降低其癌变风险和提供青春期发育所需的激素,疗效良好。
- Abstract:
- Objective To explore the clinical features,diagnoses and therapeutic strategies of complete androgen insensitivity syndrome (CAIS) in children.Methods The relevant clinical data of a child with CAIS were retrospectively reviewed."Complete androgen insensitivity syndrome" was applied as a search term in PubMed,China National Knowledge Infrastructure (CNKI) and WANFANG DATA from January 2013 to October 2023.Along with the relevant literature fulfilling the specified inclusion and exclusion criteria,general profiles,clinical manifestations,treatment protocols and follow-up results of children diagnosed as CAIS were summarized.Results Upon admission,a 13-year-old girl with primary amenorrhea was identified based upon social gender.A definite diagnosis of CAIS was confirmed through comprehensive clinical evaluations of symptoms,physical examinations,color Doppler ultrasonography for body mass evaluation,sex hormone analysis and chromosome karyotypic analysis.Bilateral laparoscopic exploration and subsequent bilateral orchiectomy were performed for cryptorchidism.Pathological diagnosis was testicular tissue atrophy and absence of spermatogenic cells in seminiferous tubules.The child was discharged postoperatively.Subsequent follow-ups revealed bilateral breast hyperplasia and a decline of sex hormone level.To date,the child fared well.Here all of 11 CAIS cases were assigned female at birth.Diagnostic age ranged from 26 days to 17 years.Primary amenorrhea (n=5) and indirect inguinal hernia (n=5) were the predominant clinical manifestations.Most girls exhibited typical female external genitalia.In 7 cases,vagina was imperforate while another case presented with a normal length and a narrow diameter.Karyotype analysis revealed 46,XY (n=10) and 47,XXY.ishYp11.3 (SRY+)(n=1).There were relocating gonads in abdomen (n=1),rejection of surgical intervention (n=1) and gonadectomy (n=9).Postoperative follow-ups revealed that 7 children recovered well and received hormone replacement therapy.The longest follow-up period was 20 years.One case developed breast hyperplasia while three cases were lost to follow-ups.Conclusions As a rare disease,CAIS usually presents as primary amenorrhea.However,it can often be misdiagnosed as an indirect inguinal hernia due to the presence of a mass in inguinal region before puberty.For girls presenting with either an indirect inguinal hernia or primary amenorrhea,clinicians should stay on a high alert for the possibility of CAIS.Differential diagnosis requires further imaging studies and chromosome karyotypic analysis while genetic testing is necessary for confirming a diagnosis.Surgical intervention should be performed as soon as possible.There is still some controversies regarding optimal timing of surgery.Gonadectomy should be performed during puberty or early adulthood for minimizing cancer risks and facilitating normal pubertal development through hormone replacement.
参考文献/References:
[1] Quigley CA,De Bellis A,Marschke KB,et al.Androgen receptor defects:historical,clinical,and molecular perspectives[J].Endocr Rev,1995,16(3):271-321.DOI:10.1210/edrv-16-3-271.
[2] Galani A,Kitsiou-Tzeli S,Sofokleous C,et al.Androgen insensitivity syndrome:clinical features and molecular defects[J].Hormones (Athens),2008,7(3):217-229.DOI:10.14310/horm.2002.1201.
[3] Hughes IA,Werner R,Bunch T,et al.Androgen insensitivity syndrome[J].Semin Reprod Med,2012,30(5):432-442.DOI:10.1055/s-0032-1324728.
[4] Costagliola G,Cosci O di Coscio M,Masini B,et al.Disorders of sexual development with XY karyotype and female phenotype:clinical findings and genetic background in a cohort from a single centre[J].J Endocrinol Invest,2021,44(1):145-151.DOI:10.1007/s40618-020-01284-8.
[5] Ahmed SF,Cheng A,Dovey L,et al.Phenotypic features,androgen receptor binding,and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome[J].J Clin Endocrinol Metab,2000,85(2):658-665.DOI:10.1210/jcem.85.2.6337.
[6] Singh S,Ilyayeva S.Androgen insensitivity syndrome//StatPearls.Treasure Island:StatPearls Publishing,2023:NBK542206.https://pubmed.ncbi.nlm.nih.gov/31194363/.
[7] Xiao X,Yang Z.Complete androgen insensitivity syndrome:a rare case report[J].Asian J Surg,2023,46(10):4503-4504.DOI:10.1016/j.asjsur.2023.04.130.
[8] Matalka L,Dean SJ,Beauchamp G,et al.An early case of complete androgen insensitivity syndrome[J].J Investig Med High Impact Case Rep,2023,11:23247096231157918.DOI:10.1177/23247096231157918.
[9] 多吉.完全型雄激素不敏感综合征1例[J].西藏医药,2023,44(3):155-156. Duo J.Complete androgen insensitivity syndrome:one case report[J].Tibetan Med,2023,44(3):155-156.
[10] Yang HJ,Wu ZF,Tian Y,et al.Yolk sac tumor in an infant with androgen insensitivity syndrome:a case report and review of the literature[J].Int J SurgPathol,2022,30(7):804-809.DOI:10.1177/10668969221085292.
[11] Wang K,Wang Q,Chen J,et al.Case report:a novel nonsense mutation in the androgen receptor gene causing the complete androgen insensitivity syndrome[J].ReprodSci,2022,29(9):2659-2663.DOI:10.1007/s43032-022-00944-9.
[12] 张文蕾,郑剑兰,李玉萍,等.完全性雄激素不敏感综合征4例分析[J].现代妇产科进展,2022,31(8):610-613,618.DOI:10.13283/j.cnki.xdfckjz.2022.08.011. Zhang WL,Zheng JL,Li YP,et al.Analysis of 4 cases of complete androgen insensitivity syndrome:a report of 4 cases[J].Prog Obstet Gynecol,2022,31(8):610-613,618.DOI:10.13283/j.cnki.xdfckjz.2022.08.011.
[13] Gamcová V,Eim J,Meixnerová I,et al.Complete androgen insensitivity syndrome-rare case of malignancy of dysgenetic gonads[J].Ceska Gynekol,2022,87(3):84-187.DOI:10.48095/cccg2022184.
[14] Barbagallo F,Cannarella R,Bertelli M,et al.Complete androgen insensitivity syndrome:from the relevance of an accurate genetic diagnosis to the challenge of clinical management.A case report[J].Medicina (Kaunas),2021,57(11):1142.DOI:10.3390/medicina57111142.
[15] Skalska K,Zió?kowski M,Skoczylas A,et al.18-Year-old patient with Klinefelter syndrome (47,XXY) and complete androgen insensitivity syndrome (CAIS)-case report[J].Gynecol Endocrinol,2021,37(6):572-575.DOI:10.1080/09513590.2021.1921139.
[16] Siminas S,Kokai G,Kenny SE.Complete androgen insensitivity syndrome associated with bilateral Sertoli cell adenomas and paratesticular leiomyomas:case report and review of the literature[J].J Pediatr Urol,2013,9(1):e31-e34.DOI:10.1016/j.jpurol.2012.06.013.
[17] Morris JM.The syndrome of testicular feminization in male pseudohermaphrodites[J].Am J Obstet Gynecol,1953,65(6):1192-1211.DOI:10.1016/0002-9378(53)90359-7.
[18] 王宇昊,陈杏林,秦超,等.1例特殊家族史的完全性雄激素不敏感综合征及其遗传学分析[J].中华男科学杂志,2022,28(7):618-621.DOI:10.13263/j.cnki.nja.2022.07.008. Wang YH,Chen XL,Qin C,et al.A case report of complete androgen insensitivity syndrome with special family history and its genetic analysis[J].Natl J Androl,2022,28(7):618-621.DOI:10.13263/j.cnki.nja.2022.07.008.
[19] Skakkebaek NE,Rajpert-De Meyts E,Main KM.Testicular dysgenesis syndrome:an increasingly common developmental disorder with environmental aspects[J].Hum Reprod,2001,16(5):972-978.DOI:10.1093/humrep/16.5.972.
[20] Han TT,Ran J,Ding XP,et al.Cytogenetic and molecular analysis of infertile Chinese men:karyotypic abnormalities,Y-chromosome microdeletions,and CAG and GGN repeat polymorphisms in the androgen receptor gene[J].Genet Mol Res,2013,12(3):2215-2226.DOI:10.4238/2013.July.8.3.
[21] 邸建永,刘丽,刘清华,等.完全型雄激素不敏感综合征一家系基因诊断并文献复习[J].天津医药,2019,47(8):858-861.DOI:10.11958/20190769. Di JY,Liu L,Liu QH,et al.Genetic diagnosis and literature review of a family with complete androgen insensitivity syndrome[J].Tianjin Med J,2019,47(8):858-861.DOI:10.11958/20190769.
[22] Berglund A,Johannsen TH,Stochholm K,et al.Incidence,prevalence,diagnostic delay,and clinical presentation of female 46,XY disorders of sex development[J].J Clin Endocrinol Metab,2016,101(12):4532-4540.DOI:10.1210/jc.2016-2248.
[23] 中华医学会儿科学分会内分泌遗传代谢学组.性发育异常的儿科内分泌诊断与治疗共识[J].中华儿科杂志,2019,57(6):410-418.DOI:10.3760/cma.j.issn.0578-1310.2019.06.003. Subspecialty Group of Endocrinologic,Hereditary and Metabolic Diseases,the Society of Pediatrics,Chinese Medical Association.Consensus statement on the diagnosis and endocrine treatment of children with disorder of sex development[J].Chin J Pediatr,2019,57(6):410-418.DOI:10.3760/cma.j.issn.0578-1310.2019.06.003.
[24] Wisniewski AB,Migeon CJ,Meyer-Bahlburg HF,et al.Complete androgen insensitivity syndrome:long-term medical,surgical,and psychosexual outcome[J].J Clin Endocrinol Metab,2000,85(8):2664-2669.DOI:10.1210/jcem.85.8.6742.
[25] 张亚南,袁诗敏,席惠,等.7例完全型雄激素不敏感综合征患者的临床及遗传学分析[J].实用妇产科杂志,2019,35(12):950-953. Zhang YN,Yuan SM,Xi H,et al.Clinical and genetic analysis of 7 patients with complete androgen insensitivity syndrome[J].J Pract Obstet Gynecol,2019,35(12):950-953.
[26] Tyutyusheva N,Mancini I,Baroncelli GI,et al.Complete androgen insensitivity syndrome:from bench to bed[J].Int J Mol Sci,2021,22(3):1264.DOI:10.3390/ijms22031264.
[27] 梁,吕逸清,谢华,等.46,XY性发育异常儿童患者性别分配结果分析[J].上海交通大学学报(医学版),2021,41(11):1412-1416.DOI:10.3969/j.issn.1674-8115.2021.11.002. Liang Y,Lyu YQ,Xie H,et al.Analysis of gender assignment in children with 46,XY disorders of sex development[J].J Shanghai Jiaotong Univ (Med Sci),2021,41(11):1412-1416.DOI:10.3969/j.issn.1674-8115.2021.11.002.
[28] Huang H,Wang CQ,Tian QJ.Gonadal tumour risk in 292 phenotypic female patients with disorders of sex development containing Y chromosome or Y-derived sequence[J].Clin Endocrinol (Oxf),2017,86(4):621-627.DOI:10.1111/cen.13255.
[29] Chaudhry S,Tadokoro-Cuccaro R,Hannema SE,et al.Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS):a retrospective case-series analysis[J].J PediatrUrol,2017,13(5):498.e1-498.e6.DOI:10.1016/j.jpurol.2017.02.013.
[30] Looijenga LHJ.Human testicular (non) seminomatous germ cell tumours:the clinical implications of recent pathobiological insights[J].J Pathol,2009,218(2):146-162.DOI:10.1002/path.2522.
[31] D?hnert U,Wünsch L,Hiort O.Gonadectomy in complete androgen insensitivity syndrome:why and when?[J].Sex Dev,2017,11(4):171-174.DOI:10.1159/000478082.
[32] Hurt WG,Bodurtha JN,McCall JB,et al.Seminoma in pubertal patient with androgen insensitivity syndrome[J].Am J Obstet Gynecol,1989,161(3):530-531.DOI:10.1016/0002-9378(89)90350-5.
[33] Deans R,Creighton SM,Liao LM,et al.Timing of gonadectomy in adult women with complete androgen insensitivity syndrome (CAIS):patient preferences and clinical evidence[J].Clin Endocrinol (Oxf),2012,76(6):894-898.DOI:10.1111/j.1365-2265.2012.04330.x.
[34] Manuel M,Katayama PK,Jones HWJr.The age of occurrence of gonadal tumors in intersex patients with a Y chromosome[J].Am J Obstet Gynecol,1976,124(3):293-300.DOI:10.1016/0002-9378(76)90160-5.
[35] Cools M,Looijenga L.Update on the pathophysiology and risk factors for the development of malignant testicular germ cell tumors in complete androgen insensitivity syndrome[J].Sex Dev,2017,11(4):175-181.DOI:10.1159/000477921.
[36] Palmert MR,Dunkel L.Clinical practice.Delayed puberty[J].N Engl J Med,2012,366(5):443-453.DOI:10.1056/NEJMcp1109290.
[37] Frank GR.Role of estrogen and androgen in pubertal skeletal physiology[J].Med Pediatr Oncol,2003,41(3):217-221.DOI:10.1002/mpo.10340.
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备注/Memo
收稿日期:2024-9-19。
基金项目:国家自然科学基金(82293660)
通讯作者:郝希伟,Email:17853296627@163.com