Androgen insensitivity syndrome overview: Difference between revisions
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==Diagnosis== | ==Diagnosis== | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
The diagnosis of AIS is determined in a 46,XY individual by the undermasculinization of the external genitalia, impaired spermatogenesis and absent or rudimentary müllerian structures. Cases of CAIS are diagnosed during abdominal surgery, delayed menarche and infertility. | The diagnosis of AIS is determined in a 46,XY individual by the undermasculinization of the external genitalia, impaired spermatogenesis and absent or rudimentary müllerian structures. Cases of CAIS are diagnosed during abdominal surgery, delayed menarche and infertility. | ||
===Physical Examination=== | ===Physical Examination=== | ||
Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Evidence of normal or increased synthesis of testosterone and its normal conversion to dihydrotestosterone, and normal or increased luteinizing hormone (LH) production by the pituitary gland AND/OR by the identification of a hemizygous pathogenic variant. | |||
===Imaging Findings=== | ===Imaging Findings=== | ||
There are no X-ray and MRI findings associated with androgen insensitivity syndrome. Findings of seminoma are observed by FDG PET/CT in androgen insensitivity syndrome.<ref name="pmid28604478">{{cite journal| author=Han EJ, O JH, Park G, Lee J| title=FDG PET/CT Image of Seminoma in Androgen Insensitivity Syndrome. | journal=Clin Nucl Med | year= 2017 | volume= 42 | issue= 8 | pages= e381-e382 | pmid=28604478 | doi=10.1097/RLU.0000000000001722 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28604478 }} </ref>. Incidental detection of Sertoli–Leydig cell tumor by FDG PET/CT imaging. <ref name="pmid19957213">{{cite journal| author=Ozülker T, Ozpaçaci T, Ozülker F, Ozekici U, Bilgiç R, Mert M| title=Incidental detection of Sertoli-Leydig cell tumor by FDG PET/CT imaging in a patient with androgen insensitivity syndrome. | journal=Ann Nucl Med | year= 2010 | volume= 24 | issue= 1 | pages= 35-9 | pmid=19957213 | doi=10.1007/s12149-009-0321-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19957213 }} </ref>. Radiology findings in the “predominantly male” phenotype including impaired development of the prostate and of the wolffian duct derivatives demonstrated by ultrasonography or genitourography. <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 neonatal ambiguity is described in more detail in the [[intersex]] article. It typically consists of pelvic ultrasound to determine presence or absence of uterus and gonads. | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There are other diagnostic studies associated with androgen insensitivity syndrome. | |||
==Treatment== | ==Treatment== | ||
| Line 54: | Line 57: | ||
===Prevention=== | ===Prevention=== | ||
Currently there are no established methods to prevent androgen insensitivity syndrome (AIS). However, various treatment options may help manage the symptoms of AIS. Genetic counseling is advisable for parents as well as the affected individuals. The use of preimplantation genetic screening, noninvasive prenatal screening and ultrasonography and laparoscopic surgery may help identify, prevent or rectify accordingly. Women with CAIS have decreased bone mineral density, regardless of timing of gonadectomy. | |||
==References== | ==References== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Androgen insensitivity syndrome (AIS) is an undervirilization syndrome in individuals with 46, XY karyotype. The undervirilization can be complete feminization or incomplete virilization with grades of ambiguity. AIS is caused by mutations in the androgen receptor, resulting in resistance to the physiologic activities of androgens. Differing degrees of resistance lead to three phenotypes: a complete form with female-appearing external genitalia, a partial form with a wide range of virilization, and a mild form with only minor undervirilization. AIS presents different challenges depending on whether resistance is complete or partial. Challenges include sex assignment, which impacts other medical decisions such as gonadectomy, hormonal replacement, and other surgical interventions. This review describes medical, psychosocial, and ethical concerns for each stage of development in complete and partial AIS, from the neonatal period to adulthood. These aspects of care should be addressed within an ethical framework by a multidisciplinary team, with the patients and families being the stakeholders in the decision-making process. [1]
Historical Perspective
Case reports compatible with CAIS date back to the 19th century, when hermaphroditism was the technical term for intersex conditions.
Classification
Androgen insensitivity syndrome (AIS) represents a spectrum of defects in androgen action and can be subdivided into three broad phenotypes such as CAIS. PAIS and MAIS.
Pathophysiology
Androgen insensitivity syndrome results from mutations of the gene encoding the androgen receptor. AIS involves variable degree of undervirilization and/or infertility in XY persons of either sex.
Causes
Androgen insensitivity syndrome is caused due to mutations in the X-linked androgen receptor gene. AR gene defects inhibit the normal development of both internal and external genital structures in 46,XY individuals, causing a variety of phenotypes ranging from male infertility to completely normal female external genitalia. [2]
Differentiating Androgen insensitivity syndrome from Other Diseases
Androgen insensitivity syndrome should be differentiated from other more common forms of male undervirilization, including Leydig cell hypoplasia, several uncommon defects of testosterone synthesis, and 5α-reductase deficiency which can produce similar genital anatomy must be excluded. [3]
Epidemiology and Demographics
CAIS has a prevalence of 2 per 100,000 to 5 per 100,000. The incidence of complete AIS is about in 5 in 100,000. (AIS) is typically characterized by evidence of feminization (i.e., undermasculinization). There is no racial predilection for Androgen insensitivity syndrome.
Risk Factors
The risk of gonadal germ cell tumor is low during childhood and adolescence but increases in later adulthood. Benign tumours of non-germ-cell origin include Sertoli cell adenoma and hamartomas.
Screening
he diagnosis of AIS is mostly made postnatally. Studies have shown that the AIS may be identified prenatally by imaging techniques and comparative study such as such as preimplantation genetic screening, noninvasive prenatal screening and ultrasonography.
Natural History, Complications, and Prognosis
Diagnosis
History and Symptoms
The diagnosis of AIS is determined in a 46,XY individual by the undermasculinization of the external genitalia, impaired spermatogenesis and absent or rudimentary müllerian structures. Cases of CAIS are diagnosed during abdominal surgery, delayed menarche and infertility.
Physical Examination
Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype.
Laboratory Findings
Evidence of normal or increased synthesis of testosterone and its normal conversion to dihydrotestosterone, and normal or increased luteinizing hormone (LH) production by the pituitary gland AND/OR by the identification of a hemizygous pathogenic variant.
Imaging Findings
There are no X-ray and MRI findings associated with androgen insensitivity syndrome. Findings of seminoma are observed by FDG PET/CT in androgen insensitivity syndrome.[4]. Incidental detection of Sertoli–Leydig cell tumor by FDG PET/CT imaging. [5]. Radiology findings in the “predominantly male” phenotype including impaired development of the prostate and of the wolffian duct derivatives demonstrated by ultrasonography or genitourography. [3] Evaluation of neonatal ambiguity is described in more detail in the intersex article. It typically consists of pelvic ultrasound to determine presence or absence of uterus and gonads.
Other Diagnostic Studies
There are other diagnostic studies associated with androgen insensitivity syndrome.
Treatment
Medical Therapy
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. [6]
Surgery
Surgical approach to the Androgen insensitivity syndrome involves vaginal dilation or gonadectomy or determination of sex which depend on various factors such as the type of AIS, age, sex and preventive measures to be taken in adolescence and adulthood.
Prevention
Currently there are no established methods to prevent androgen insensitivity syndrome (AIS). However, various treatment options may help manage the symptoms of AIS. Genetic counseling is advisable for parents as well as the affected individuals. The use of preimplantation genetic screening, noninvasive prenatal screening and ultrasonography and laparoscopic surgery may help identify, prevent or rectify accordingly. Women with CAIS have decreased bone mineral density, regardless of timing of gonadectomy.
References
- ↑ Chen MJ, Vu BM, Axelrad M, Dietrich JE, Gargollo P, Gunn S; et al. (2015). "Androgen Insensitivity Syndrome: Management Considerations from Infancy to Adulthood". Pediatr Endocrinol Rev. 12 (4): 373–87. PMID 26182482.
- ↑ Galani A, Kitsiou-Tzeli S, Sofokleous C, Kanavakis E, Kalpini-Mavrou A (2008). "Androgen insensitivity syndrome: clinical features and molecular defects". Hormones (Athens). 7 (3): 217–29. PMID 18694860.
- ↑ 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) - ↑ Han EJ, O JH, Park G, Lee J (2017). "FDG PET/CT Image of Seminoma in Androgen Insensitivity Syndrome". Clin Nucl Med. 42 (8): e381–e382. doi:10.1097/RLU.0000000000001722. PMID 28604478.
- ↑ Ozülker T, Ozpaçaci T, Ozülker F, Ozekici U, Bilgiç R, Mert M (2010). "Incidental detection of Sertoli-Leydig cell tumor by FDG PET/CT imaging in a patient with androgen insensitivity syndrome". Ann Nucl Med. 24 (1): 35–9. doi:10.1007/s12149-009-0321-x. PMID 19957213.
- ↑ Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA (2015). "Androgen insensitivity syndrome". Best Pract Res Clin Endocrinol Metab. 29 (4): 569–80. doi:10.1016/j.beem.2015.04.005. PMID 26303084.