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==Overview==
==Overview==


A multidisciplinary approach is recommended for clinical management from infancy through to adulthood. Hormone replacement therapy is needed following gonadectomy. Patients who choose to retain the gonads are at risk of developing germ cell tumors for which sensitive circulating tumor markers may soon become available. <ref name="pmid26303084">{{cite journal| author=Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA| title=Androgen insensitivity syndrome. | journal=Best Pract Res Clin Endocrinol Metab | year= 2015 | volume= 29 | issue= 4 | pages= 569-80 | pmid=26303084 | doi=10.1016/j.beem.2015.04.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26303084  }} </ref>
A multidisciplinary approach is recommended for clinical management from [[infancy]] up to adulthood. [[Hormone replacement therapy]] is needed following gonadectomy. Patients who have decided to retain their [[gonads]] are considered to be at risk for developing [[germ cell tumors]] and for these the sensitive circulating [[tumor markers]] may become available soon.


==Medical Therapy==
==Medical Therapy==
===General management===
===General management===
Management of androgen insensitivity syndrome should address: <ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>
Management of androgen insensitivity syndrome should address:<ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>


*Functional issues
*Functional issues
*Sexual issues
*Sexual issues
*Psychological issues such as disclosure
*[[Psychological]] issues such as disclosure
*Gonadectomy and subsequent '''hormone replacement'''
*Gonadectomy and subsequent [[Hormone replacement therapy|hormone replacement]]
*Creation of a functional vagina, and provision of genetic advice.
*Creation of a functional [[vagina]], and provision of genetic advice
*Care needs to be individualised, flexible, and holistic.
*Care needs to be individualized, flexible, and holistic
*Management is dependent wholly on a multidisciplinary team.
*Management is dependent wholly on a multidisciplinary team


===Specific management based on the type of AIS===
===Specific management based on the type of AIS===


====Management of CAIS====
====Management of CAIS (complete androgen insensitivity syndrome)====


Treatment of manifestations:  
Treatment of manifestations:  


*In order to prevent testicular malignancy, treatment of CAIS may include either removal of the testes after puberty when feminization is complete or prepubertal gonadectomy accompanied by estrogen replacement therapy. The risk of gonadal germ cell tumor is low during childhood and adolescence but increases in later adulthood.  
*Treatment options for CAIS may include either removal of the testes after puberty when [[feminization]] is complete so as to prevent [[testicular]] [[malignancy]] OR along with [[estrogen replacement therapy]], prepubertal gonadectomy is advised. The risk of gonadal [[germ cell tumor]] is low during childhood and [[adolescence]] but increases in later adulthood.  
*Additional treatment for CAIS may include vaginal dilatation to avoid dyspareunia.
*In order to avoid [[dyspareunia]], vaginal dilatation may be recommended as an additional treatment for CAIS.
*Management issues in CAIS involve timing of gonadectomy, appropriate hormone replacement therapy and assessment of the need for vaginal dilation or rarely, vaginal surgery.<ref name="pmid23044881">{{cite journal| author=Hughes IA, Werner R, Bunch T, Hiort O| title=Androgen insensitivity syndrome. | journal=Semin Reprod Med | year= 2012 | volume= 30 | issue= 5 | pages= 432-42 | pmid=23044881 | doi=10.1055/s-0032-1324728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23044881  }} </ref>
*Timing of gonadectomy, appropriate [[hormone replacement therapy]] and assessment of the need for vaginal [[dilation]] or rarely, vaginal surgery are the issues involved in the management of CAIS.<ref name="pmid23044881">{{cite journal| author=Hughes IA, Werner R, Bunch T, Hiort O| title=Androgen insensitivity syndrome. | journal=Semin Reprod Med | year= 2012 | volume= 30 | issue= 5 | pages= 432-42 | pmid=23044881 | doi=10.1055/s-0032-1324728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23044881  }} </ref>
*Expert psychological counseling is mandatory to manage the disconnect between chromosomal, gonadal and phenotypic sex and to choreograph the evolving process of disclosure from late childhood through to maturity.<ref name="pmid23044881">{{cite journal| author=Hughes IA, Werner R, Bunch T, Hiort O| title=Androgen insensitivity syndrome. | journal=Semin Reprod Med | year= 2012 | volume= 30 | issue= 5 | pages= 432-42 | pmid=23044881 | doi=10.1055/s-0032-1324728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23044881  }} </ref>
*Expert [[psychological]] counseling is mandatory to manage the disconnect between [[chromosomal]], gonadal and [[phenotypic]] sex and to choreograph the evolving process of disclosure from late childhood through to maturity.<ref name="pmid23044881">{{cite journal| author=Hughes IA, Werner R, Bunch T, Hiort O| title=Androgen insensitivity syndrome. | journal=Semin Reprod Med | year= 2012 | volume= 30 | issue= 5 | pages= 432-42 | pmid=23044881 | doi=10.1055/s-0032-1324728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23044881  }} </ref>
*'''Hormone Replacement Therapy:''' Starting dose of 2 μg daily from roughly 11 years of age. This dose is increased in increments of 2–4 μg over about 2 years to reach a daily dose of 30 μg (unpublished). Thereafter, and in women who have a gonadectomy after puberty, several preparations are available, including the natural oestrogen estradiol, which can be given orally or transdermally. Synthetic oestrogens can be given in the form of the combined oral contraceptive pill. Some evidence supports the use of natural oestrogens as transdermal hormone replacement therapy because this administration method might be more physiological than oral delivery. <ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>
*'''[[Hormone Replacement Therapy]]:''' Starting dose of 2 μg daily from roughly 11 years of age. This dose is increased in increments of 2 - 4 μg over about 2 years to reach a daily dose of 30 μg. Thereafter, and in women who have a gonadectomy after [[puberty]], several preparations are available, including the natural [[estrogen]] [[estradiol]], which can be given orally or transdermally. Synthetic [[estrogens]] can be given in the form of the combined [[oral contraceptive pill]]. Some evidence supports the use of natural [[estrogens]] as transdermal [[hormone replacement therapy]] because this administration method might be more [[physiological]] than oral delivery. <ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>


====Management of PAIS====
====Management of PAIS (partial androgen insensitivity syndrome)====
*Treatment of PAIS in individuals with predominantly female genitalia is similar to treatment of CAIS, but is more likely to include prepubertal gonadectomy to help avoid increasing clitoromegaly at the time of puberty.
*Treatment of PAIS is similar to treatment of CAIS in individuals with predominantly female genitalia, but in order to help avoid increasing [[clitoromegaly]] at the time of [[puberty]]. The pre-pubertal gonadectomy procedure is advised.
*In individuals with PAIS and ambiguous or predominantly male genitalia, the tendency has been for parents and healthcare professionals to assign sex of rearing after an expert evaluation has been completed.
*In individuals with PAIS and [[Ambiguous genitalia|ambiguous]] or predominantly male genitalia, the tendency has been for parents and healthcare professionals to assign sex of rearing after an expert evaluation has been completed.
*Individuals with PAIS who are raised as males may undergo urologic surgery such as orchiopexy and hypospadias repair. <ref name="pmid22698698">{{cite journal |vauthors=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J |title=Androgen insensitivity syndrome |journal=Lancet |volume=380 |issue=9851 |pages=1419–28 |year=2012 |pmid=22698698 |doi=10.1016/S0140-6736(12)60071-3 |url=}}</ref>
*Individuals with PAIS and raised as males may undergo [[urologic]] surgery such as [[orchiopexy|orchipexy]] and [[hypospadias]] repair. <ref name="pmid22698698">{{cite journal |vauthors=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J |title=Androgen insensitivity syndrome |journal=Lancet |volume=380 |issue=9851 |pages=1419–28 |year=2012 |pmid=22698698 |doi=10.1016/S0140-6736(12)60071-3 |url=}}</ref>
*Individuals with PAIS who are raised as females and who undergo gonadectomy after puberty may need combined estrogen and androgen replacement therapy. <ref name="pmid22698698">{{cite journal |vauthors=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J |title=Androgen insensitivity syndrome |journal=Lancet |volume=380 |issue=9851 |pages=1419–28 |year=2012 |pmid=22698698 |doi=10.1016/S0140-6736(12)60071-3 |url=}}</ref>
*Individuals with PAIS and raised as females and who undergo gonadectomy after puberty may need combined [[Estrogen-replacement therapy|estrogen]] and [[Androgen replacement therapy|androgen]] replacement therapy.<ref name="pmid22698698">{{cite journal |vauthors=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J |title=Androgen insensitivity syndrome |journal=Lancet |volume=380 |issue=9851 |pages=1419–28 |year=2012 |pmid=22698698 |doi=10.1016/S0140-6736(12)60071-3 |url=}}</ref>


====Management of MAIS====
====Management of MAIS (mild androgen insensitivity syndrome)====
*Males with MAIS may require mammoplasty for gynecomastia.
*Males with MAIS may require [[mammoplasty]] for [[gynecomastia]].
*A trial of androgen pharmacotherapy may help improve virilization in infancy.
*A trial of [[androgen]] pharmacotherapy may help improve [[virilization]] in infancy.
*It is best if the diagnosis of AIS is explained to the affected individual and family in an empathic environment, with both professional and family support.
*It is best if the diagnosis of AIS is explained to the affected individual and family in an empathic environment, with both professional and family support.


===Psychosocial management===
===Psychosocial management===
Psychosocial support is central to the multidisciplinary approach to management of complete androgen insensitivity syndrome. Presenting adolescents and parents of children with the disorder will have to make important decisions at diagnosis about treatments and the timing and extent of any surgical interventions. Concerns should focus on assimilation of the disconnect between chromosomal, gonadal, and phenotypic sex and its implications. Most centres caring for patients with disorders of sex development provide specialist psychological support.<ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>
*[[Psychosocial]] support plays a major role in a multidisciplinary approach in managing complete androgen insensitivity syndrome.
*When the diagnosis is made, [[adolescents]] and parents of children with the disorder would have to make crucial decisions regarding treatments, timing and the extent of any surgical interventions. Major focus has to be laid on assimilation of the disparities between [[chromosomal]], gonadal, and [[phenotypic]] sex and its implications. Specialist [[psychological]] support is provided in most centers caring for patients with [[Disorder of sexual development|disorders of sex development]] ([[Disorder of sexual development|DSD]]).<ref name="pmid22698698">{{cite journal| author=Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J| title=Androgen insensitivity syndrome. | journal=Lancet | year= 2012 | volume= 380 | issue= 9851 | pages= 1419-28 | pmid=22698698 | doi=10.1016/S0140-6736(12)60071-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22698698  }} </ref>


===Prevention of secondary manifestations===
===Prevention of secondary manifestations===
Regular weight-bearing exercises and supplemental calcium and vitamin D are recommended to optimize bone health; bisphosphonate therapy may be indicated for those with evidence of decreased bone mineral density and/or multiple fractures. <ref name="pmid20301602">{{cite journal |vauthors=Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, Gottlieb B, Trifiro MA |title= |journal= |volume= |issue= |pages= |year= |pmid=20301602 |doi= |url=}}</ref>
*Supplemental [[calcium]] and [[vitamin D]] along with regular weight-bearing exercises and are advised to optimize bone health.
*[[Bisphosphonate]] therapy may be beneficial for individuals with decreased [[bone mineral density]] and a history of multiple [[fractures]]. <ref name="pmid20301602">{{cite journal |vauthors=Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, Gottlieb B, Trifiro MA |title= |journal= |volume= |issue= |pages= |year= |pmid=20301602 |doi= |url=}}</ref>


===Surveillance===
===Surveillance===
Periodic reevaluation for gynecomastia during puberty in individuals assigned a male sex; monitoring of bone mineral density through DEXA scanning in adults.
* Periodic reevaluation for [[gynecomastia]] during [[puberty]] in individuals assigned a male sex; monitoring of [[bone mineral density]] (BMD) through [[DEXA scan|DEXA]] scanning in adults. <ref name="pmid20301602">{{cite journal |vauthors=Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, Gottlieb B, Trifiro MA |title= |journal= |volume= |issue= |pages= |year= |pmid=20301602 |doi= |url=}}</ref>


===Evaluation of relatives at risk===
===Evaluation of relatives at risk===
In an apparently asymptomatic older or younger sibling who has normal external female genitalia and who has not yet undergone menarche, a karyotype can be done first. For those phenotypic females who have a 46,XY karyotype, molecular genetic testing for the known AR variant in the family can be pursued next. If the AR variant in the family is not known, androgen binding assays could be considered.
A [[karyotype]] analysis can be done first In an apparently asymptomatic older or younger sibling who has normal external female genitalia and who has not yet undergone [[menarche]]. Molecular genetic testing for [[androgen receptor]] ([[Androgen receptor|AR]]) variant in the family would be advised next for the [[phenotypic]] females who have a 46,XY [[karyotype]]. Androgen binding assays should be considered if the [[androgen receptor]] ([[Androgen receptor|AR]]) variant in the family is undocumented.


===Genetic counseling===
===Genetic counseling===
*AIS is inherited in an X-linked manner. Affected 46,XY individuals are almost always infertile. Each offspring of a female known to carry an AR pathogenic variant (heterozygote) is at a 25% risk for each of the following:  
*[[Androgen receptor]] ([[Androgen receptor|AR]]) mutations are inherited and transmitted in an [[X linked]] manner.
*In XY-offspring, 50% are affected and XX offspring 50% of them are a healthy carrier. <ref name="pmid28670533">{{cite journal |vauthors=Akella RR |title=Mutational Analysis of Androgen Receptor Gene in Two Families with Androgen Insensitivity |journal=Indian J Endocrinol Metab |volume=21 |issue=4 |pages=520–523 |year=2017 |pmid=28670533 |pmc=5477437 |doi=10.4103/ijem.IJEM_345_16 |url=}}</ref>
*Affected 46XY individuals are almost always [[infertile]].
*The risk of [[transmission]] is negligible in sporadic cases. <ref name="pmid28670533">{{cite journal |vauthors=Akella RR |title=Mutational Analysis of Androgen Receptor Gene in Two Families with Androgen Insensitivity |journal=Indian J Endocrinol Metab |volume=21 |issue=4 |pages=520–523 |year=2017 |pmid=28670533 |pmc=5477437 |doi=10.4103/ijem.IJEM_345_16 |url=}}</ref>
*In any case of de-novo mutation of the [[androgen receptor]] ([[Androgen receptor|AR]]) gene, germline [[mosaicism]] cannot be excluded and counseling the families has to be handled cautiously. <ref name="pmid28670533">{{cite journal |vauthors=Akella RR |title=Mutational Analysis of Androgen Receptor Gene in Two Families with Androgen Insensitivity |journal=Indian J Endocrinol Metab |volume=21 |issue=4 |pages=520–523 |year=2017 |pmid=28670533 |pmc=5477437 |doi=10.4103/ijem.IJEM_345_16 |url=}}</ref>
*The children of a female known to carry an [[androgen receptor]] ([[Androgen receptor|AR]])  pathogenic variant ([[heterozygote]]) are at a 25% risk for:  
**Getting affected and having 46XY karyotype
**Getting affected and having 46XY karyotype
**Would be a carrier and has a 46XX karyotype
**Would not be a carrier and has a 46XX karyotype


**Having a 46,XY karyotype and being affected
*If the pathogenic variant in the family is known, [[prenatal testing]] for [[pregnancies]] at increased risk and also carrier testing for at-risk relatives are possible .
**Having a 46,XY karyotype and being unaffected
**Having a 46,XX karyotype and being a carrier
**Having a 46,XX karyotype and not being a carrier
 
*Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant in the family is known.


==References==
==References==

Latest revision as of 12:36, 12 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]

Overview

A multidisciplinary approach is recommended for clinical management from infancy up to adulthood. Hormone replacement therapy is needed following gonadectomy. Patients who have decided to retain their gonads are considered to be at risk for developing germ cell tumors and for these the sensitive circulating tumor markers may become available soon.

Medical Therapy

General management

Management of androgen insensitivity syndrome should address:[1]

  • Functional issues
  • Sexual issues
  • Psychological issues such as disclosure
  • Gonadectomy and subsequent hormone replacement
  • Creation of a functional vagina, and provision of genetic advice
  • Care needs to be individualized, flexible, and holistic
  • Management is dependent wholly on a multidisciplinary team

Specific management based on the type of AIS

Management of CAIS (complete androgen insensitivity syndrome)

Treatment of manifestations:

Management of PAIS (partial androgen insensitivity syndrome)

  • Treatment of PAIS is similar to treatment of CAIS in individuals with predominantly female genitalia, but in order to help avoid increasing clitoromegaly at the time of puberty. The pre-pubertal gonadectomy procedure is advised.
  • In individuals with PAIS and ambiguous or predominantly male genitalia, the tendency has been for parents and healthcare professionals to assign sex of rearing after an expert evaluation has been completed.
  • Individuals with PAIS and raised as males may undergo urologic surgery such as orchipexy and hypospadias repair. [1]
  • Individuals with PAIS and raised as females and who undergo gonadectomy after puberty may need combined estrogen and androgen replacement therapy.[1]

Management of MAIS (mild androgen insensitivity syndrome)

  • Males with MAIS may require mammoplasty for gynecomastia.
  • A trial of androgen pharmacotherapy may help improve virilization in infancy.
  • It is best if the diagnosis of AIS is explained to the affected individual and family in an empathic environment, with both professional and family support.

Psychosocial management

  • Psychosocial support plays a major role in a multidisciplinary approach in managing complete androgen insensitivity syndrome.
  • When the diagnosis is made, adolescents and parents of children with the disorder would have to make crucial decisions regarding treatments, timing and the extent of any surgical interventions. Major focus has to be laid on assimilation of the disparities between chromosomal, gonadal, and phenotypic sex and its implications. Specialist psychological support is provided in most centers caring for patients with disorders of sex development (DSD).[1]

Prevention of secondary manifestations

Surveillance

Evaluation of relatives at risk

A karyotype analysis can be done first In an apparently asymptomatic older or younger sibling who has normal external female genitalia and who has not yet undergone menarche. Molecular genetic testing for androgen receptor (AR) variant in the family would be advised next for the phenotypic females who have a 46,XY karyotype. Androgen binding assays should be considered if the androgen receptor (AR) variant in the family is undocumented.

Genetic counseling

  • Androgen receptor (AR) mutations are inherited and transmitted in an X linked manner.
  • In XY-offspring, 50% are affected and XX offspring 50% of them are a healthy carrier. [4]
  • Affected 46XY individuals are almost always infertile.
  • The risk of transmission is negligible in sporadic cases. [4]
  • In any case of de-novo mutation of the androgen receptor (AR) gene, germline mosaicism cannot be excluded and counseling the families has to be handled cautiously. [4]
  • The children of a female known to carry an androgen receptor (AR) pathogenic variant (heterozygote) are at a 25% risk for:
    • Getting affected and having 46XY karyotype
    • Getting affected and having 46XY karyotype
    • Would be a carrier and has a 46XX karyotype
    • Would not be a carrier and has a 46XX karyotype
  • If the pathogenic variant in the family is known, prenatal testing for pregnancies at increased risk and also carrier testing for at-risk relatives are possible .

References

  1. 1.0 1.1 1.2 1.3 1.4 Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J (2012). "Androgen insensitivity syndrome". Lancet. 380 (9851): 1419–28. doi:10.1016/S0140-6736(12)60071-3. PMID 22698698.
  2. 2.0 2.1 Hughes IA, Werner R, Bunch T, Hiort O (2012). "Androgen insensitivity syndrome". Semin Reprod Med. 30 (5): 432–42. doi:10.1055/s-0032-1324728. PMID 23044881.
  3. 3.0 3.1 Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean L, Bird TD, Ledbetter N, Mefford HC, Smith R, Stephens K, Gottlieb B, Trifiro MA. PMID 20301602. Vancouver style error: initials (help); Missing or empty |title= (help)
  4. 4.0 4.1 4.2 Akella RR (2017). "Mutational Analysis of Androgen Receptor Gene in Two Families with Androgen Insensitivity". Indian J Endocrinol Metab. 21 (4): 520–523. doi:10.4103/ijem.IJEM_345_16. PMC 5477437. PMID 28670533.

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