Androgen insensitivity syndrome pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(113 intermediate revisions by 4 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Androgen insensitivity syndrome}}
{{Androgen insensitivity syndrome}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{ARK}}


==Overview==
==Overview==
Androgen insensitivity syndrome is due to [[hormone]] resistance which may be due to defective [[androgen receptor]] ([[Androgen receptor|AR]]) function by either abnormal [[androgen receptor]] ([[Androgen receptor|AR]]) binding, decreased receptor binding, or impaired [[androgen receptor]] ([[Androgen receptor|AR]]) binding. AIS is an [[X linked]] disorder. The development of androgen insensitivity syndrome is a result of [[genetic mutations]] of the [[androgen receptor]] ([[Androgen receptor|AR]]) gene located on the chromosome Xq11-12. Associated conditions include [[primary amenorrhea]], [[infertility]] and [[dyspareunia]].


==Pathophysiology==
==Pathophysiology==
Androgen insensitivity syndrome results from [[mutation]]s of the gene encoding the [[androgen]] [[receptor (biochemistry)|receptor]]. It has also been called ''androgen resistance'' in the medical literature. The nature of the resulting problem varies according to the structure and sensitivity of the abnormal receptor. Most of the forms of AIS involve variable degrees of [[virilization|undervirilization]] and/or [[infertility]] in [[XY sex-determination system|XY]] persons of either sex. A woman with complete androgen insensitivity syndrome (CAIS) has a nearly normal female body despite a 46XY [[karyotype]] and undescended  [[testis|testes]], a condition termed ''testicular feminization'' in the past.  
===Pathogenesis===
*Androgen resistance may develop during fetal development and after birth.
*The hormone resistance may be due to defective [[androgen receptor]] ([[Androgen receptor|AR]]) function by either abnormal [[androgen receptor]] ([[Androgen receptor|AR]]) binding, decreased receptor binding, or impaired [[androgen receptor]] ([[Androgen receptor|AR]])  binding. <ref name="FlierUnderhill1992">{{cite journal|last1=Flier|first1=Jeffrey S.|last2=Underhill|first2=Lisa H.|last3=Griffin|first3=James E.|title=Androgen Resistance — The Clinical and Molecular Spectrum|journal=New England Journal of Medicine|volume=326|issue=9|year=1992|pages=611–618|issn=0028-4793|doi=10.1056/NEJM199202273260906}}</ref><ref name="BrownMaes1982">{{cite journal|last1=Brown|first1=Terry R.|last2=Maes|first2=Marc|last3=Rothwell|first3=Stephen W.|last4=Migeon|first4=Claude J.|title=Human Complete Androgen Insensitivity with Normal Dihydrotestosterone Receptor Binding Capacity in Cultured Genital Skin Fibroblasts: Evidence for a Qualitative Abnormality of the Receptor*|journal=The Journal of Clinical Endocrinology & Metabolism|volume=55|issue=1|year=1982|pages=61–69|issn=0021-972X|doi=10.1210/jcem-55-1-61}}</ref><ref name="Griffin1979">{{cite journal|last1=Griffin|first1=James E.|title=Testicular Feminization Associated with a Thermolabile Androgen Receptor in Cultured Human Fibroblasts|journal=Journal of Clinical Investigation|volume=64|issue=6|year=1979|pages=1624–1631|issn=0021-9738|doi=10.1172/JCI109624}}</ref>
*A spectrum of [[phenotypes]] may be caused due to [[missense mutations]] in the [[androgen receptor]] ([[Androgen receptor|AR]]) [[protein]]. The two important domains of the [[receptor protein]] namely DBD and LDB domains are the ones wherein the most frequent [[missense mutations]] are found.<ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref><ref name="pmid2626022">{{cite journal |vauthors=Brinkmann AO, Faber PW, van Rooij HC, Kuiper GG, Ris C, Klaassen P, van der Korput JA, Voorhorst MM, van Laar JH, Mulder E |title=The human androgen receptor: domain structure, genomic organization and regulation of expression |journal=J. Steroid Biochem. |volume=34 |issue=1-6 |pages=307–10 |year=1989 |pmid=2626022 |doi= |url=}}</ref>
*The [[phenotype|phenotypic]] variability impacts and translates the degree to which ligand-binding and [[receptor]] functions are disrupted by different substitutions.<ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref><ref name="pmid1752359">{{cite journal |vauthors=McPhaul MJ, Marcelli M, Tilley WD, Griffin JE, Wilson JD |title=Androgen resistance caused by mutations in the androgen receptor gene |journal=FASEB J. |volume=5 |issue=14 |pages=2910–5 |year=1991 |pmid=1752359 |doi= |url=}}</ref>
*The genetic background has an influence on the resulting [[phenotype]] as a result of the same [[mutation]] which may lead to different forms of AIS within a family.<ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref><ref name="pmid9245853">{{cite journal |vauthors=Evans BA, Hughes IA, Bevan CL, Patterson MN, Gregory JW |title=Phenotypic diversity in siblings with partial androgen insensitivity syndrome |journal=Arch. Dis. Child. |volume=76 |issue=6 |pages=529–31 |year=1997 |pmid=9245853 |pmc=1717223 |doi= |url=}}</ref>
*Mutations in the [[androgen receptor]] ([[Androgen receptor|AR]]) gene helps as a trusted tool for the diagnosis and molecular subclassification of AIS. The resulting [[phenotype]] is affected by the kind of amino acid substitution occurring due to [[mutation]].<ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref>
*Information regarding the mutation in the [[androgen receptor]] ([[Androgen receptor|AR]]) and its functional consequences helps in determining the genotype-phenotype correlation, to improve and better manage the cases of male [[pseudohermaphroditism]] pertaining to surgery of the [[genitalia]], gonadectomy and gender assignment. <ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref>
*The lack of virilization of external genitalia is due to the failure of genital folds to fuse and to form [[scrotum]] and [[penis]].
*The agenesis of the [[fallopian tubes]], [[uterus]], [[cervix]] and proximal [[vagina]] is due to the simultaneous [[testicular]] production of [[mullerian inhibiting factor]] which regresses the mullerian structures.
*In CAIS (complete androgen insensitivity syndrome), the development of the [[wolffian duct]] and the differentiation of male external [[genitalia]] do not occur correctly, and the [[Mullerian ducts]] regress due to the presence of anti-Mullerian hormone (AMH) produced by the [[sertoli cells]] of normally developed [[gonads]]. The residual [[Mullerian structures]] exist in approximately one third of patients. <ref name="pmid18930210">{{cite journal |vauthors=Nichols JL, Bieber EJ, Gell JS |title=Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants |journal=Fertil. Steril. |volume=91 |issue=3 |pages=932.e15–8 |year=2009 |pmid=18930210 |doi=10.1016/j.fertnstert.2008.09.027 |url=}}</ref> <ref name="pmid25191030">{{cite journal |vauthors=Ozdemir O, Sari ME, Akmut E, Selimova V, Unal T, Atalay CR |title=Complete androgen insensitivity syndrome with a large gonadal serous papillary cystadenofibroma |journal=J Hum Reprod Sci |volume=7 |issue=2 |pages=148–50 |year=2014 |pmid=25191030 |pmc=4150143 |doi=10.4103/0974-1208.138875 |url=}}</ref>
*The female [[phenotype]] along with [[breast]] development is a result of the peripheral [[aromatization]] of [[testosterone]] into [[estrogen]].<ref name="pmid17161333">{{cite journal |vauthors=Hughes IA, Deeb A |title=Androgen resistance |journal=Best Pract. Res. Clin. Endocrinol. Metab. |volume=20 |issue=4 |pages=577–98 |year=2006 |pmid=17161333 |doi=10.1016/j.beem.2006.11.003 |url=}}</ref>
*As a result of the defective [[androgen receptor]] ([[Androgen receptor|AR]]) due to imperfect feedback mechanism of [[testosterone]] at the [[pituitary]] and [[hypothalamus]] there are elevated levels of serum [[testosterone]], [[FSH]] and [[LH]] observed.
*[[Testosterone]] biosynthetic defects are ruled out by the normal serum 17α hydroxyprogesterone, [[DHEA]] and [[androstenedione]] levels.<ref name="pmid9389232">{{cite journal |vauthors=Viner RM, Teoh Y, Williams DM, Patterson MN, Hughes IA |title=Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK |journal=Arch. Dis. Child. |volume=77 |issue=4 |pages=305–9 |year=1997 |pmid=9389232 |pmc=1717340 |doi= |url=}}</ref>
*Sufficient peripheral conversion of [[testosterone]] is indicative of normal [[estradiol]] level.


Major changes in the understanding and management of the various forms of AIS have occurred since 1990. Laboratory research has greatly expanded our understanding of the molecular mechanisms of the clinical features, including a rare neuromuscular disorder. More importantly, patient advocacy groups for AIS and other [[intersex]] conditions have increased public awareness of these disorders, helped revise the understanding of [[gender identity]], emphasized the value of accurate and sophisticated information for patients, and induced physicians to re-evaluate the effectiveness of the [[intersex surgery|surgical corrections]] attempted in past decades. Surgery is increasingly seen as an elective option even for the more [[ambiguous genitalia|ambiguous]] conditions.
[[Image:Androgen_dependencies_of_male_genital_tissues.png|thumb|600px|left|By Jonathan.Marcus (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons]]
===Normal function of androgens and the androgen receptor [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=14504652&dopt=Abstract]===
[[Image:Human_sexual_differentiation.gif|thumb|600px|center|By Jonathan.Marcus (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons]]
Understanding the effects of androgen insensitivity begins with an understanding of the normal effects of [[testosterone]] in male and female development. The principal mammalian androgens are testosterone and its more potent [[metabolite]], [[dihydrotestosterone]] (DHT).
 
The [[androgen receptor]] (AR) is a large [[protein]] of at least 910 [[amino acid]]s. Each molecule consists of a portion which binds the androgen, a [[zinc finger]] portion that binds to [[DNA]] in [[steroid]] sensitive areas of nuclear [[chromatin]], and an area that controls [[Transcription (genetics)|transcription]].
 
Testosterone diffuses from the circulation into the [[cytoplasm]] of a target [[Cell (biology)|cell]]. Some is metabolized to [[estradiol]], some reduced to DHT, and some remains as testosterone (T). Both T and DHT can bind and activate the androgen receptor, though DHT does so with more potent and prolonged effect. As DHT (or T) binds to the receptor, a portion of the protein is cleaved. The AR-DHT combination dimerizes by combining with a second AR-DHT, both are [[phosphorylation|phosphorylated]], and the entire complex moves into the [[cell nucleus]] and binds to androgen response elements on the [[promoter]] region of androgen-sensitive target genes. The [[Transcription (genetics)|transcription]] effect is amplified or inhibited by coactivators or corepressors. 
 
Although testosterone can be produced directly and indirectly from [[ovary|ovaries]] and [[adrenal]]s later in life, the primary source of testosterone in early [[fetus|fetal]] life is the [[testis|testes]], and it plays a major role in human [[sexual differentiation]]. Before birth, testosterone induces the [[primary sex characteristics]] of males. At [[puberty]], testosterone is primarily responsible for the [[secondary sex characteristic]]s of males.
 
*See [[Testosterone]] article for fuller discussion of androgen sources and the role of testosterone in normal human development.
*See [[Sexual differentiation]] for a brief but fuller overview of human sexual differentiation and biological sex differences.
====Prenatal effects of testosterone in 46,XY fetus====
In a normal fetus with a [[46,XY]] karyotype, the presence of the [[SRY]] gene induces testes to form on the [[genital ridge]]s in the fetal [[abdomen]] a few weeks after [[conception]]. By 6 weeks of gestation, [[genitalia|genital]] anatomies of XY and XX fetuses are still indistinguishable, consisting of a tiny underdeveloped [[genital tubercle|button]] of tissue able to become a [[phallus]], and a urogenital midline opening flanked by folds of skin able to become either [[labia]] or [[scrotum]]. By the 7th week, fetal testes begin to produce testosterone and release it into the blood.
 
Directly and as DHT, testosterone acts on the skin and tissues of the genital area and by 12 weeks of gestation, has produced a recognizable male, with a growing [[penis]] with a [[urethra]]l opening at the tip, and a [[perineum]] fused and thinned into a scrotum, ready for the testes. Evidence suggests that this "remodelling" of the genitalia can only occur during this period of fetal life; if not complete by about 13 weeks, no amount of testosterone later will move the urethral opening or close a [[vagina]]-like opening.
 
For the remainder of gestation, the principal known effect of testosterone and DHT is continued growth of the penis and internal [[wolffian ducts|wolffian]] derivatives (part of [[prostate]], [[epididymis]], [[seminal vesicle]]s, and [[vas deferens]]).
 
====Early postnatal effects of testosterone in 46,XY infants====
Testosterone levels are low at birth but rise within weeks, remaining at normal male [[puberty|pubertal]] levels for about 2 months before declining to the low, barely detectable childhood levels. The biological function of this rise is unknown. Animal research suggests a contribution to brain differentiation.
 
====Pubertal effects of testosterone in 46,XY children====
At [[puberty]], many of the early physical changes in both sexes are androgenic (adult-type [[body odor]], increased oiliness of skin and hair, acne, [[pubic hair]], [[Underarm hair|axillary hair]], fine upper lip and [[sideburn]] hair).
 
As puberty progresses, later secondary sex characteristics in males are nearly entirely due to androgens (continued growth of the penis, maturation of spermatogenic tissue and [[fertility]], beard, deeper voice, masculine jaw and musculature, body hair, heavier bones). In males, the major pubertal changes attributable to [[estradiol]] are growth acceleration, [[epiphysis|epiphyseal closure]], termination of growth, and (if it occurs) [[gynecomastia]].


===Genetics===
===Genetics===
*AIS is an [[X linked]] disorder. <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>
*A high proportion of [[De novo mutation|De novo mutations]] arise after the [[zygote]] stage which occur at a high rate within the [[androgen receptor]] ([[Androgen receptor|AR]]) gene.<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>
*Spontaneous [[mutations]] in the [[androgen receptor]] ([[Androgen receptor|AR]]) gene results in androgen insensitivity syndrome even without any family history.<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 development of androgen insensitivity syndrome is a result of [[genetic mutations]] of the [[androgen receptor]] ([[Androgen receptor|AR]]) gene located on the chromosome Xq11-12.<ref name="pmid24339553">{{cite journal |vauthors=Kota SK, Gayatri K, Kota SK, Jammula S |title=Genetic analysis of a family with complete androgen insensitivity syndrome |journal=Indian J Hum Genet |volume=19 |issue=3 |pages=355–7 |year=2013 |pmid=24339553 |pmc=3841565 |doi=10.4103/0971-6866.120820 |url=}}</ref><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>
*Different [[mutations]] in the [[androgen receptor]] ([[Androgen receptor|AR]]) gene leads to varied clinical [[phenotypes]].<ref name="pmid26806084">{{cite journal |vauthors=Li L, Liu WM, Liu MX, Zheng SQ, Zhang JX, Che FY, Liu SG |title=A missense mutation in the androgen receptor gene causing androgen insensitivity syndrome in a Chinese family |journal=Asian J. Androl. |volume=19 |issue=2 |pages=260–261 |year=2017 |pmid=26806084 |pmc=5312231 |doi=10.4103/1008-682X.172647 |url=}}</ref><ref name="Brinkmann2001">{{cite journal|last1=Brinkmann|first1=Albert O.|title=Molecular basis of androgen insensitivity|journal=Molecular and Cellular Endocrinology|volume=179|issue=1-2|year=2001|pages=105–109|issn=03037207|doi=10.1016/S0303-7207(01)00466-X}}</ref>
*There have been more than 800 [[mutations]] in  the [[androgen receptor]] [[Androgen receptor|(]][[Androgen receptor|AR]][[Androgen receptor|)]] gene reported in AIS patients. <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>


{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
[[Image:XlinkRecessiveAIS.png|thumb|600px|center|By U.S. National Library of Medicine; David-Sarah Hopwood (Originally from http://ghr.nlm.nih.gov/) [Public domain], via Wikimedia Commons]]
| colspan="3" style="background: #4479BA; text-align: center;" | {{fontcolor|#FFF|'''Molecular Genetic Testing Used in Androgen Insensitivity Syndrome'''}}
|+
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF|Gene}}
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF|Test Method}}
! style="background: #4479BA; padding: 5px 5px;" colspan=1 | {{fontcolor|#FFFFFF|Proportion of 46,XY Probands w/a Pathogenic Variant 2 Detectable by This Method}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="2;" | AR
| style="padding: 5px 5px; background: #F5F5F5;" | Sequence analysis
| style="padding: 5px 5px; background: #F5F5F5;" |
*~95%-97%
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Gene-targeted deletion/duplication analysis
| style="padding: 5px 5px; background: #F5F5F5;" |
*~3%-5%
|-
|}


==Associated Conditions==
*[[Primary amenorrhea]]
*[[Infertility]]
*[[Dyspareunia]]
*Common [[Testicular tumor|testicular tumors]] seen in the Androgen insensitivity syndrome are: <ref name="pmid25395750">{{cite journal |vauthors=Bhaskararao G, Himabindu Y, Nayak SR, Sriharibabu M |title=Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome |journal=J Hum Reprod Sci |volume=7 |issue=3 |pages=221–3 |year=2014 |pmid=25395750 |pmc=4229800 |doi=10.4103/0974-1208.142498 |url=}}</ref>
:*[[Germ cell tumors]]
:*Sex cord tumors ([[seminoma]])
:*[[Sertoli Cell Tumor|Sertoli cell tumors]]
:*[[Leydig cell tumor|Leydig cell tumors]]
:*[[Hamartomas]]


[[Image:aisdiag.png|thumb|left|240px|Schematic of AIS affecting an Androgen Receptor]]
==Gross Pathology==
Because the Androgen Insensitivity Syndrome gives rise to ambiguity between the genetic and the phenotypic gender, we will use the convention 46,XY to designate a genotypic male, and 46,XX to designate a genotypic female. By this convention, a person with Androgen Insensitivity Syndrome is a 46,XY but a phenotypic female.
*Complete androgen insensitivity syndrome in a 30 years old woman presenting with [[primary amenorrhea]].<ref name="pmid28270903">{{cite journal |vauthors=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K, Ahmed A |title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report |journal=Pan Afr Med J |volume=25 |issue= |pages=199 |year=2016 |pmid=28270903 |pmc=5326263 |doi=10.11604/pamj.2016.25.199.10758 |url=}}</ref>. <ref name="pmid26301004">{{cite journal |vauthors=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M, Rahali DM, Dehayni M |title=[Complete androgen insensitivity syndrome: report of two cases and review of literature] |language=French |journal=Pan Afr Med J |volume=20 |issue= |pages=400 |year=2015 |pmid=26301004 |pmc=4524922 |doi=10.11604/pamj.2015.20.400.6760 |url=}}</ref>


The Androgen Insensitivity Syndrome has been linked to mutations in ''AR'', the gene for the human Androgen Receptor, located at Xq11-12 (i.e. on the [[X chromosome]]). Thus, it is an [[X-linked recessive]] trait, causing minimal or no effects in 46,XX people. 
<gallery>
 
[[Image:XlinkRecessive.jpg|thumb|left|200px|X-linked recessive inheritance.]]
However, 46,XX women with a single mutated copy of the AR gene can be "carriers" of AIS, and their 46,XY children (male) will have a 50% chance of having the syndrome. As in some other [[X-linked recessive]] conditions, carrier mothers may display some minor traits of the condition: AIS carriers often have reduced [[underarm hair|axillary]] and [[pubic hair]], and reduced normal adolescent [[Acne vulgaris|acne]].
 
Except in the rare instance of a new mutation, a person affected with AIS has inherited his/her single X chromosome with the defective gene from his/her mother, who may have an affected sibling. Generally the condition caused by a familial mutation will affect family members similarly, though differing degrees of severity occasionally occur in different relatives with apparently the same mutation. Carrier testing is now available for relatives at risk when a diagnosis of AIS is made in a family member.
 
Over 100 ''AR'' mutations causing various forms of AIS have been reported. In general, the milder types of AIS (4 and 5 in the list below) are caused by simple [[missense mutation]]s with single [[codon]]/single [[amino acid]] difference, while CAIS and the nearly complete forms result from mutations that more severely affect the shape and structure of the protein. About one third of cases of AIS are new mutations rather than familial. A single case of CAIS attributed to an abnormality of the AF-1 coactivator (rather than ''AR'' itself) has been reported (OMIM 300274).
<br clear="left"/>
 
===1. Complete AIS===
People with CAIS are girls or women with internal testes, 46,XY karyotypes, and normal female bodies by external appearance except for some exceptions. The [[vagina]] is not as deep, and there are no [[ovary|ovaries]] or [[uterus]]— hence no [[menses]] or [[fertility]]. [[Gender identity]] is almost always female.
 
===2. Incomplete or partial AIS===
As with CAIS, girls and women with PAIS also have a 46,XY karyotype, testes, and a female body lacking a uterus, ovaries and full vagina. However, the mutations associated with PAIS do not entirely eliminate all responsiveness to androgens, and mild testosterone effects occur.
 
The most obvious testosterone effect seen in PAIS is pubic and axillary hair, which are usually normal. The clitoris may be enlarged, and the labia partially fused, though these features are usually not pronounced enough to cause noticeable ambiguity of the genitalia at birth, or may be subtle enough to be ascribed to normal anatomic variation. Internally, traces of undeveloped wolffian structures (epididymis, vas deferens, seminal vesicles, ejaculatory ducts) may be present.
 
===3. Reifenstein syndrome===
Androgen receptor mutations associated with more intermediate degrees of androgen responsiveness can result in more intermediate degrees of masculinization before birth and obvious ambiguity of the genitalia. Of the five clinical forms of AIS described here, this is the only one likely to result in uncertainty about a baby's sex at birth, and the most likely to be diagnosed in infancy.
 
The testes of a 46,XY fetus produce AMH and testosterone.  In Reifenstein syndrome, as in CAIS, PAIS, and normal males, the AMH suppresses development of a uterus, fallopian tubes, and upper vagina. However, unlike CAIS and PAIS, fetal testosterone has a significant effect on the external genitalia, producing a phallus smaller than a typical penis but larger than a typical clitoris.
 
This most obvious birth defect, somewhat midway between male and female, nearly always leads to referral to a pediatric endocrinologist and a full genetic, anatomic, and hormonal evaluation.
 
===4. Infertile male syndrome===
Androgen receptor mutations have also been discovered in men with normal internal and external genitalia but infertility due to absence of sperm ([[azoospermia]]). Androgenic body hair is normal and gynecomastia uncommon. Some have mildly elevated testosterone and LH levels but this is not invariable. Several surveys suggest that androgen receptor mutations can be found in 30-40% of men with [[infertility]] due to otherwise unexplained oligospermia or azoospermia. AIS may also explain most cases of a rarer form of male infertility, the Del Castillo or Sertoli-cell-only syndrome.


===5. Undervirilized fertile male syndrome===
Image: AIS_-_Front and side view of the patient.jpg|Front and side view of the patient by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
Some ''AR'' mutations with mildly reduced sensitivity cause mild undervirilization. These men have normally formed internal and external genitalia but a small penis. Androgenic body hair may be sparser than unaffected relatives. Ejaculate volume may be reduced, though sperm density is normal. Few examples of this variant of AIS have been reported, but unlike the previously listed phenotypes, many of these men are fertile.


===6. X-linked spinal and bulbar atrophy syndrome===
Image: AIS_-_Clinical aspect of the vagina.jpg|Clinical aspect of the vagina by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
[[Kennedy disease]] is an X-linked spinal-bulbar muscle atrophy syndrome associated with mutations of the androgen receptor. Like the other forms of AIS described above, it affects only males. The distinctive ''AR'' mutation of Kennedy disease, reported in 1991, involves multiplied CAG repeats in the first exon. The mechanism by which this type of mutation causes neuromuscular disease, while complete insensitivity does not, is not yet understood.


Since the neuromuscular disease was first described in 1968 many kindreds have been reported. Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. Early signs often include weakness of tongue and mouth muscles, fasciculations, and gradually increasing weakness of proximal limb muscles. In some cases, premature muscle exhaustion began in adolescence. Neuromuscular management is supportive, and the disease progresses very slowly and often does not lead to extreme disability.
Image: AIS_-_Intra- abdominal testes - laparoscopic aspect.jpg|Intra- abdominal testes - Laparoscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>


Endocrine manifestations of this disorder are variable and only rarely include undervirilization of internal or external genitalia. In the majority evidence of altered androgen sensitivity is restricted to exaggerated or persistent adolescent [[gynecomastia]], and the mildly high LH, testosterone, and estradiol levels characteristic of other forms of AIS. In other words, most people affected with Kennedy disease are relatively normal XY men with normal fertility and normal or minimally reduced virilization.
Image: AIS_-_The excised testis - Macroscopic aspect.jpg|The excised testis - Macroscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue= | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
 
==Associated Conditions==
 
 
==Gross Pathology==
Complete androgen insensitivity syndrome in a 30 years old woman who presented primary amenorrhea.<ref name="pmid28270903">{{cite journal |vauthors=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K, Ahmed A |title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report |journal=Pan Afr Med J |volume=25 |issue= |pages=199 |year=2016 |pmid=28270903 |pmc=5326263 |doi=10.11604/pamj.2016.25.199.10758 |url=}}</ref>.
<ref name="pmid26301004">{{cite journal |vauthors=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M, Rahali DM, Dehayni M |title=[Complete androgen insensitivity syndrome: report of two cases and review of literature] |language=French |journal=Pan Afr Med J |volume=20 |issue= |pages=400 |year=2015 |pmid=26301004 |pmc=4524922 |doi=10.11604/pamj.2015.20.400.6760 |url=}}</ref>
 
<gallery>
Image: AIS_-_Front and side view of the patient.jpg|Front and side view of the patient
Image: AIS_-_absence of pubic and axillary hair.jpg| Normal female morphotype but absence of pubic and axillary hair
Image: AIS_-_Clinical aspect of the vagina.jpg|Clinical aspect of the vagina
Image: AIS_-_Intra- abdominal testes - Laparoscopic aspect.jpg|Intra- abdominal testes - laparoscopic aspect
Image: AIS_-_The excised testis - Macroscopic aspect.jpg|The excised testis - Macroscopic aspect
</gallery>
</gallery>


==Microscopic Pathology==
==Microscopic Pathology==


*Histopathology shows two testes with atrophic seminiferous tubules containing only Sertoli cells, associated to a Leydig cells hyperplasia.<ref name="pmid26301004">{{cite journal| author=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M et al.| title=[Complete androgen insensitivity syndrome: report of two cases and review of literature]. | journal=Pan Afr Med J | year= 2015 | volume= 20 | issue=  | pages= 400 | pmid=26301004 | doi=10.11604/pamj.2015.20.400.6760 | pmc=4524922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26301004  }} </ref>
*Histopathology of testes shows atrophic [[seminiferous tubules]] containing only [[sertoli cells]], associated to a [[leydig cells]] [[hyperplasia]].<ref name="pmid26301004">{{cite journal| author=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M et al.| title=[Complete androgen insensitivity syndrome: report of two cases and review of literature]. | journal=Pan Afr Med J | year= 2015 | volume= 20 | issue=  | pages= 400 | pmid=26301004 | doi=10.11604/pamj.2015.20.400.6760 | pmc=4524922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26301004  }} </ref>
*On histological examination, the well-limited nodule circumscribed by a thin capsule consists of atrophic Servolian tubes with a very small interstitial tissue with rare Leydig cells. This nodule corresponds to a well differentiated tumor with Sertoli-Leydig cells. <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
*The well-limited nodule presents as a circumscribed structure with a thin capsule consisting of atrophic servolian tubes with a very small interstitial tissue with rare [[leydig cells]]. This nodule corresponds to a well differentiated tumor with [[sertoli-leydig cells]]. <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
*The gonads on histopathological examination show the following: <ref name="pmid25395750">{{cite journal |vauthors=Bhaskararao G, Himabindu Y, Nayak SR, Sriharibabu M |title=Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome |journal=J Hum Reprod Sci |volume=7 |issue=3 |pages=221–3 |year=2014 |pmid=25395750 |pmc=4229800 |doi=10.4103/0974-1208.142498 |url=}}</ref>
:*Thickened [[tunica albuginea]]
:*[[Seminiferous tubules]] with primary and secondary spermatogonia and [[sertoli cells]]
:*Intertubular leydig cells were seen along with peritubular fibrosis


<gallery>
<gallery>
Image: AIS_-_Testes_-_atrophy of the seminiferous tubules - Histopathological aspect, HE staining.jpg| Testes - Atrophy of the seminiferous tubules - Histopathological aspect, HE staining.<ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
Image:AIS_-_Testes_-_atrophy_of_the_seminiferous_tubules_-_Histopathological_aspect,_HE_staining.jpg|Testes - Atrophy of the seminiferous tubules - Histopathological aspect, HE staining by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). <ref name="pmid28270903">{{cite journal| author=Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K et al.| title=Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report. | journal=Pan Afr Med J | year= 2016 | volume= 25 | issue=  | pages= 199 | pmid=28270903 | doi=10.11604/pamj.2016.25.199.10758 | pmc=5326263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28270903  }} </ref>
Image: AIS_-_testicular parenchyma.jpg| testicular parenchyma of lobulated architecture, made of seminiferous tubes of atrophic appearance; B) these tubes are lined with Sertolia cells, with no obvious signs of spermatogenesis the interstitium is fibrous with rare clusters of Leydig cells.<ref name="pmid26301004">{{cite journal| author=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M et al.| title=[Complete androgen insensitivity syndrome: report of two cases and review of literature]. | journal=Pan Afr Med J | year= 2015 | volume= 20 | issue=  | pages= 400 | pmid=26301004 | doi=10.11604/pamj.2015.20.400.6760 | pmc=4524922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26301004  }} </ref>
 
Image:AIS_-_testicular_parenchyma.jpg|Testicular parenchyma of lobulated architecture, made of seminiferous tubes of atrophic appearance; these tubes are lined with Sertolia cells, with no obvious signs of spermatogenesis the interstitium is fibrous with rare clusters of Leydig cells by Boutaina Lachiri et al from the Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2015;20:400. CC BY-NC 3.0, Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0). <ref name="pmid26301004">{{cite journal| author=Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M et al.| title=[Complete androgen insensitivity syndrome: report of two cases and review of literature]. | journal=Pan Afr Med J | year= 2015 | volume= 20 | issue=  | pages= 400 | pmid=26301004 | doi=10.11604/pamj.2015.20.400.6760 | pmc=4524922 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26301004  }} </ref>
</gallery>
</gallery>


Latest revision as of 14:04, 19 October 2017

Androgen insensitivity syndrome Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Androgen insensitivity syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Androgen insensitivity syndrome pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Androgen insensitivity syndrome pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Androgen insensitivity syndrome pathophysiology

CDC on Androgen insensitivity syndrome pathophysiology

Androgen insensitivity syndrome pathophysiology in the news

Blogs on Androgen insensitivity syndrome pathophysiology

Directions to Hospitals Treating Androgen insensitivity syndrome

Risk calculators and risk factors for Androgen insensitivity syndrome pathophysiology

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

Androgen insensitivity syndrome is due to hormone resistance which may be due to defective androgen receptor (AR) function by either abnormal androgen receptor (AR) binding, decreased receptor binding, or impaired androgen receptor (AR) binding. AIS is an X linked disorder. The development of androgen insensitivity syndrome is a result of genetic mutations of the androgen receptor (AR) gene located on the chromosome Xq11-12. Associated conditions include primary amenorrhea, infertility and dyspareunia.

Pathophysiology

Pathogenesis

By Jonathan.Marcus (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons
By Jonathan.Marcus (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

Genetics

By U.S. National Library of Medicine; David-Sarah Hopwood (Originally from http://ghr.nlm.nih.gov/) [Public domain], via Wikimedia Commons

Associated Conditions

Gross Pathology

  • Front and side view of the patient by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

    Front and side view of the patient by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

  • Clinical aspect of the vagina by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

    Clinical aspect of the vagina by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

  • Intra- abdominal testes - Laparoscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

    Intra- abdominal testes - Laparoscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

  • The excised testis - Macroscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

    The excised testis - Macroscopic aspect by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

Microscopic Pathology

  • Testes - Atrophy of the seminiferous tubules - Histopathological aspect, HE staining by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

    Testes - Atrophy of the seminiferous tubules - Histopathological aspect, HE staining by Regragui Souhail et al from The Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2016;25:199. Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). [17]

  • Testicular parenchyma of lobulated architecture, made of seminiferous tubes of atrophic appearance; these tubes are lined with Sertolia cells, with no obvious signs of spermatogenesis the interstitium is fibrous with rare clusters of Leydig cells by Boutaina Lachiri et al from the Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2015;20:400. CC BY-NC 3.0, Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0). [18]

    Testicular parenchyma of lobulated architecture, made of seminiferous tubes of atrophic appearance; these tubes are lined with Sertolia cells, with no obvious signs of spermatogenesis the interstitium is fibrous with rare clusters of Leydig cells by Boutaina Lachiri et al from the Pan African Medical Journal - ISSN 1937-8688. Pan Afr Med J. 2015;20:400. CC BY-NC 3.0, Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0). [18]

References

  1. ↑ Flier, Jeffrey S.; Underhill, Lisa H.; Griffin, James E. (1992). "Androgen Resistance — The Clinical and Molecular Spectrum". New England Journal of Medicine. 326 (9): 611–618. doi:10.1056/NEJM199202273260906. ISSN 0028-4793.
  2. ↑ Brown, Terry R.; Maes, Marc; Rothwell, Stephen W.; Migeon, Claude J. (1982). "Human Complete Androgen Insensitivity with Normal Dihydrotestosterone Receptor Binding Capacity in Cultured Genital Skin Fibroblasts: Evidence for a Qualitative Abnormality of the Receptor*". The Journal of Clinical Endocrinology & Metabolism. 55 (1): 61–69. doi:10.1210/jcem-55-1-61. ISSN 0021-972X.
  3. ↑ Griffin, James E. (1979). "Testicular Feminization Associated with a Thermolabile Androgen Receptor in Cultured Human Fibroblasts". Journal of Clinical Investigation. 64 (6): 1624–1631. doi:10.1172/JCI109624. ISSN 0021-9738.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Kota SK, Gayatri K, Kota SK, Jammula S (2013). "Genetic analysis of a family with complete androgen insensitivity syndrome". Indian J Hum Genet. 19 (3): 355–7. doi:10.4103/0971-6866.120820. PMC 3841565. PMID 24339553.
  5. ↑ Brinkmann AO, Faber PW, van Rooij HC, Kuiper GG, Ris C, Klaassen P, van der Korput JA, Voorhorst MM, van Laar JH, Mulder E (1989). "The human androgen receptor: domain structure, genomic organization and regulation of expression". J. Steroid Biochem. 34 (1–6): 307–10. PMID 2626022.
  6. ↑ McPhaul MJ, Marcelli M, Tilley WD, Griffin JE, Wilson JD (1991). "Androgen resistance caused by mutations in the androgen receptor gene". FASEB J. 5 (14): 2910–5. PMID 1752359.
  7. ↑ Evans BA, Hughes IA, Bevan CL, Patterson MN, Gregory JW (1997). "Phenotypic diversity in siblings with partial androgen insensitivity syndrome". Arch. Dis. Child. 76 (6): 529–31. PMC 1717223. PMID 9245853.
  8. ↑ Nichols JL, Bieber EJ, Gell JS (2009). "Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants". Fertil. Steril. 91 (3): 932.e15–8. doi:10.1016/j.fertnstert.2008.09.027. PMID 18930210.
  9. ↑ Ozdemir O, Sari ME, Akmut E, Selimova V, Unal T, Atalay CR (2014). "Complete androgen insensitivity syndrome with a large gonadal serous papillary cystadenofibroma". J Hum Reprod Sci. 7 (2): 148–50. doi:10.4103/0974-1208.138875. PMC 4150143. PMID 25191030.
  10. ↑ Hughes IA, Deeb A (2006). "Androgen resistance". Best Pract. Res. Clin. Endocrinol. Metab. 20 (4): 577–98. doi:10.1016/j.beem.2006.11.003. PMID 17161333.
  11. ↑ Viner RM, Teoh Y, Williams DM, Patterson MN, Hughes IA (1997). "Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK". Arch. Dis. Child. 77 (4): 305–9. PMC 1717340. PMID 9389232.
  12. ↑ 12.0 12.1 12.2 12.3 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.
  13. ↑ Li L, Liu WM, Liu MX, Zheng SQ, Zhang JX, Che FY, Liu SG (2017). "A missense mutation in the androgen receptor gene causing androgen insensitivity syndrome in a Chinese family". Asian J. Androl. 19 (2): 260–261. doi:10.4103/1008-682X.172647. PMC 5312231. PMID 26806084.
  14. ↑ Brinkmann, Albert O. (2001). "Molecular basis of androgen insensitivity". Molecular and Cellular Endocrinology. 179 (1–2): 105–109. doi:10.1016/S0303-7207(01)00466-X. ISSN 0303-7207.
  15. ↑ 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.
  16. ↑ 16.0 16.1 Bhaskararao G, Himabindu Y, Nayak SR, Sriharibabu M (2014). "Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome". J Hum Reprod Sci. 7 (3): 221–3. doi:10.4103/0974-1208.142498. PMC 4229800. PMID 25395750.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 Souhail R, Amine S, Nadia A, Tarik K, Khalid EK, Abdellatif K, Ahmed A (2016). "Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report". Pan Afr Med J. 25: 199. doi:10.11604/pamj.2016.25.199.10758. PMC 5326263. PMID 28270903.
  18. ↑ 18.0 18.1 18.2 Lachiri B, Hakimi I, Boudhas A, Guelzim K, Kouach J, Oukabli M, Rahali DM, Dehayni M (2015). "[Complete androgen insensitivity syndrome: report of two cases and review of literature]". Pan Afr Med J (in French). 20: 400. doi:10.11604/pamj.2015.20.400.6760. PMC 4524922. PMID 26301004.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Androgen_insensitivity_syndrome_pathophysiology&oldid=1377092"