Androgen Insensitivity Syndrome: Diagnosis and Treatment

Androgen Insensitivity Syndrome is a genetic disorder that leads to decreased action of the androgen receptor, making them insensitive to action by testosterone in the body. This results in externally female characteristics in an individual who is genetically male with an X Y chromosome pair (They are 46, XY).

The disease occurs as a spectrum from complete to partial insensitivity, therefore leading to varied presentations from a normal-appearing female with the absence of menstruation to males with some feminine physical characteristics, or just infertility. The gene responsible for the inactive androgen receptor is on the X chromosome and is inherited from the mother who is a carrier, meaning she possesses the gene but doesn’t express the disease. This condition is fairly common occurring in 2-5 individuals per 100,000. Complete androgen insensitivity is the most common form encountered.

Clinical Features of Complete Androgen insensitivity Syndrome

They may present in adolescence or in childhood for varied complaints.

• Primary amenorrhea: this is the absence of onset of menstrual bleeding in a young woman. This is the most common cause for presentation to the doctor
• Normal breast development and female body type
• Minimal axillary and pubic hair
• Short and blind vagina with an absent uterus
• Groin mass or hernia: this is due to the testes which persist in the individual and can be found in infancy or childhood too.

Diagnosis of Complete Androgen Insensitivity Syndrome

The diagnosis is usually considered in a young woman presenting with the classical features described above or in an infant with groin swellings. The following tests are carried out to confirm the diagnosis:

• Karyotype: this is an analysis of the chromosomes in the body. Individuals with Androgen Insensitivity syndrome have 46 chromosomes with X and Y for sex chromosomes (genetically male)
• Gene sequencing: the region on the X chromosome that codes for the androgen receptor is sequenced to look for mutations responsible for inactivating the receptor.
• Abdominal imaging with an ultrasound or MRI is required to look for the testes in the abdomen. Imaging also shows the absence of female reproductive organs (the uterus and ovary)
• Blood test for hormones: the levels of testosterone may be low in young children, but reaches male levels after puberty and can facilitate diagnosis

Complications of Complete Androgen insensitivity syndrome

There is a risk of cancer arising from the testes if left in the body. This risk has been found to be quite small in recent studies. It is recommended to surgically remove the testes in adulthood to prevent cancer

Infertility: The absence of appropriate internal genital organs render the individual incapable of bearing children.

Management of Complete Androgen insensitivity syndrome

It is important to understand that there is no treatment to correct this condition or reverse it even if suspected at an early stage of development.

The management revolves around psychological support to the individual and their families towards understanding the condition and to help them choose options to live a healthy life.

• Surgical correction of external genitalia may be required in some. Vaginoplasty is offered to women with a small, blind vagina who experience difficulty during sexual intercourse.
• The testes are usually left till completion of growth, as premature removal may compromise height. After reaching adult height, the testes are removed surgically to prevent cancer.

References

• Complete androgen insensitivity syndrome | Genetic and Rare Diseases Information Centre (GARD) – an NCATS Program [Internet]. [cited 2018 May 28].
• Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Androgen insensitivity syndrome. Lancet. 2012 Oct 20;380(9851):1419–28.