Abstract
Objective
Complete androgen insensitivity syndrome (CAIS) is caused by mutations in the androgen receptor (AR) gene, leading to androgen resistance. Early recognition is critical for optimal management. To evaluate clinical presentations, hormonal profiles, genetic characteristics, and decisions regarding gonadectomy in pediatric CAIS. Factors influencing gonadectomy, including malignancy risk, gonadal function, and psychological well-being were assessed.
Methods
Medical records of 16 children with genetically confirmed CAIS patients, aged 3 days-18 years, diagnosed between 2004 and 2024 at a tertiary referral center were retrospectively reviewed. Clinical, hormonal, genetic, and histological data were analyzed.
Results
Twelve patients (75%) were diagnosed prepubertally, most commonly due to inguinal hernia. Familial recurrence occurred in four cases (25%). Novel pathogenic AR variants not previously reported in public databases were identified in three patients. Prepubertal patients with hormone data (n=5) demonstrated Anti-Müllerian hormone>150 pM. Pubertal patients (n=9) had markedly elevated testosterone levels [median at 1361.3 ng/dL, range 367-3460 ng/dL]. Gonadal biopsy was performed in three cases (19%). Gonadal preservation was recommended in 11 children (69%), while five (31%) underwent gonadectomy followed by estrogen replacement therapy.
Conclusion
Most CAIS cases in this pediatric cohort were detected early through inguinal hernia or family screening. Delayed gonadectomy allowed spontaneous pubertal development and feminization. While gonadectomy results in lifelong hormone dependence and may raise identity-related concerns, surveillance-based gonadal preservation appears safe during childhood. The identification of novel AR variants expands the mutational spectrum of CAIS and highlights the need for multicenter registries and improved biomarkers to optimize individualized care.
Keywords: Androgen-insensitivity syndrome, amenorrhea, castration
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References
Bertelloni S, Dati E, Baroncelli GI, Hiort O. Hormonal management of complete androgen insensitivity syndrome from adolescence onward. Horm Res Paediatr. 2011;76:428-433. Epub 2011 Nov 29
Tyutyusheva N, Mancini I, Baroncelli GI, D’Elios S, Peroni D, Meriggiola MC, Bertelloni S. Complete androgen insensitivity syndrome: from bench to bed. Int J Mol Sci. 2021;22:1264.
Batista RL, Costa EMF, Rodrigues AS, Gomes NL, Faria JA Jr, Nishi MY, Arnhold IJP, Domenice S, Mendonca BB. Androgen insensitivity syndrome: a review. Arch Endocrinol Metab. 2018;62:227-235.
Cheikhelard A, Thibaud E, Morel Y, Jaubert F, Lortat-Jacob S, Polak M, Nihoul-Fekete C. Complete androgen insensitivity syndrome: diagnosis and management. Expert Rev Endocrinol Metab. 2009;4:565-573.
Hannema SE, Scott IS, Rajpert-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208:518-527.
Edelsztein NY, Grinspon RP, Schteingart HF, Rey RA. Anti-Müllerian hormone as a marker of steroid and gonadotropin action in the testis of children and adolescents with disorders of the gonadal axis. Int J Pediatr Endocrinol. 2016;2016:20. Epub 2016 Oct 28
Hughes IA, Werner R, Bunch T, Hiort O. Androgen insensitivity syndrome. Semin Reprod Med. 2012;30:432-442. Epub 2012 Oct 8
Lanciotti L, Cofini M, Leonardi A, Bertozzi M, Penta L, Esposito S. Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS). Int J Environ Res Public Health. 2019;16:1268.
Chen Z, Li P, Lyu Y, Wang Y, Gao K, Wang J, Lan F, Chen F. Molecular genetics and general management of androgen insensitivity syndrome. Intractable Rare Dis Res. 2023;12:71-77.
Barros BA, Oliveira LR, Surur CRC, Barros-Filho AA, Maciel-Guerra AT, Guerra-Junior G. Complete androgen insensitivity syndrome and risk of gonadal malignancy: systematic review. Ann Pediatr Endocrinol Metab. 2021;26:19-23. Epub 2021 Mar 31
Tack LJW, Maris E, Looijenga LHJ, Hannema SE, Audi L, Köhler B, Holterhus PM, Riedl S, Wisniewski A, Flück CE, Davies JH, T’Sjoen G, Lucas-Herald AK, Evliyaoglu O, Krone N, Iotova V, Marginean O, Balsamo A, Verkauskas G, Weintrob N, Ellaithi M, Nordenström A, Verrijn Stuart A, Kluivers KB, Wolffenbuttel KP, Ahmed SF, Cools M. Management of gonads in adults with androgen insensitivity: an international survey. Horm Res Paediatr. 2018;90:236-246. Epub 2018 Oct 18.
Morris JM. The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol. 1953;65:1192-1211.
Viner RM, Teoh Y, Williams DM, Patterson MN, Hughes IA. Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK. Arch Dis Child. 1997;77:305-309.
Deeb A, Hughes IA. Inguinal hernia in female infants: a cue to check the sex chromosomes? BJU Int. 2005;96:401-403.
Practice Committee of American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril. 2008;90(Suppl 5):S219-S225
Papadimitriou DT, Linglart A, Morel Y, Chaussain JL. Puberty in subjects with complete androgen insensitivity syndrome. Horm Res. 2006;65:126-131. Epub 2006 Feb 16
Bouvattier C, Carel JC, Lecointre C, David A, Sultan C, Bertrand AM, Morel Y, Chaussain JL. Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene. J Clin Endocrinol Metab. 2002;87:29-32.
Josso N, Rey RA. What Does AMH tell us in pediatric disorders of sex development? Front Endocrinol (Lausanne). 2020;11:619.
Döhnert U, Wünsch L, Hiort O. Gonadectomy in complete androgen insensitivity syndrome: why and when? Sex Dev. 2017;11:171-174. Epub 2017 Jul 19
Brunner F, Fliegner M, Krupp K, Rall K, Brucker S, Richter-Appelt H. Gender role, gender identity and sexual orientation in CAIS („XY-Women”) compared with subfertile and infertile 46,XX women. J Sex Res. 2016;53:109-124. Epub 2015 Jul 2
Fliegner M, Richter-Appelt H, Krupp K, Brucker SY, Rall K, Brunner F. Living with permanent infertility: A German study on attitudes toward motherhood in individuals with Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS). Health Care Women Int. 2018;39:1295-1315. Epub 2018 Oct 26
Fliegner M, Krupp K, Brunner F, Rall K, Brucker SY, Briken P, Richter-Appelt H. Sexual life and sexual wellness in individuals with complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS). J Sex Med. 2014;11:729-742. Epub 2013 Oct 25
Auer MK, Birnbaum W, Hartmann MF, Holterhus PM, Kulle A, Lux A, Marshall L, Rall K, Richter-Unruh A, Werner R, Wudy SA, Hiort O. Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome. Endocrine. 2022;76:722-732. Epub 2022 Mar 8
