Introduction
The disorder known as androgen insensitivity syndrome, formerly known as testicular feminization, is an X-linked recessive trait that impacts adolescent and precocious sexual development. Genetically, those with this syndrome are male; each cell contains one X and one Y chromosome. They may exhibit predominantly female external sex features or indicators of both male and female sexual development because their bodies cannot react to particular male sex hormones (known as androgens).
The X-linked recessive trait prevents chromosomally male individuals from successfully masculinizing their external genitalia. Depending on the degree of remaining receptor function, this lack of virilization can either be a complete androgen insensitivity syndrome (CAIS) or a partial androgen insensitivity syndrome (PAIS).
46, XY karyotypes are shared by people with both partial androgen insensitivity syndrome and total androgen insensitivity syndrome. Female external genitalia with normal labia, clitoris, and vaginal introitus are present in people with full androgen insensitivity syndrome. With partial androgen insensitivity syndrome, the phenotypic can range from mildly virilized female external genitalia (clitoromegaly absent of other external defects) to mildly undervirilized male external genitalia (hypospadias or smaller penile size).
What Causes Androgen Insensitivity Syndrome?
Androgen insensitivity syndrome is caused by mutations in the androgen receptor gene. This gene gives instructions for producing an androgen receptor protein. Cells can react to androgens, which are hormones (like testosterone) that control the development of male sexuality. In both men and women, androgens and androgen receptors play additional crucial roles, such as controlling hair growth and sex drive. Mutations in the androgen receptor gene prohibit androgen receptors from functioning correctly, which reduces or eliminates a cell's ability to respond to androgens. The predominant sex traits of an affected person might range from predominantly female to predominantly masculine, depending on the degree of androgen insensitivity.
What Are the Types of Androgen Insensitivity Syndrome?
There are two primary classifications for the syndrome:
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Complete androgen insensitivity syndrome (CIAS).
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Partial androgen insensitivity syndrome (PIAS).
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Mild androgen insensitivity syndrome (MAIS).
Complete androgen insensitivity syndrome develops when the body is unable to use androgens. The effects of this type of ailment include:
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Females like outward sex traits.
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Lack a uterus and are unable to conceive a child because they do not menstruate (infertile).
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They often have a female gender identity and are reared as females.
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Male internal sex organs (testes), which are improperly positioned in the pelvis or abdomen, are present in affected individuals.
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If left untreated, undescended testes have a slight probability of developing cancer in the future.
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Lack of hair in the pubic region and beneath the arms.
When the body's tissues are only partially susceptible to the actions of androgens, androgen insensitivity syndrome manifests in its partial and moderate forms. Partial androgen insensitivity, often known as Reifenstein syndrome, can cause:
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The external genitals of a person may appear partially developed male or female, or they may not be clearly one or the other.
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They could have a gender identity that is either masculine or feminine, depending on how they were reared.
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Those with mild androgen insensitivity have male sex traits from birth, although they are frequently sterile and have a propensity for breast expansion during puberty.
How Androgen Insensitivity Syndrome Can Be Diagnosed?
PAIS is frequently diagnosed right after birth by examining a baby's genitals. However, CAIS or MAIS may not become apparent until the age of 11 or 12, when puberty begins. This is when a healthcare provider may notice problems. A child with CAIS may or may not have menstrual periods or pubic hair. A child with MAIS may retain a small penis or develop breast tissue. During puberty, undescended testicles can also herniation or bulge through a hole in the abdominal wall. If the child has surgery for an inguinal hernia, healthcare providers may discover undescended testicles.
Since androgen insensitivity syndrome does not exclusively exhibit the phenotypes associated with androgen sensitivity, other potential causes must be thoroughly ruled out before diagnosing androgen insensitivity syndrome.
Clinical signs of androgen insensitivity syndrome include:
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A small vagina.
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Partial or total regression of Müllerian structures.
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Bilateral nondysplastic testes.
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Decreased spermatogenesis and virilization.
Laboratory findings include:
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The 46, XY karyotype.
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Normal or increased levels of postpubertal testosterone.
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Normal or increased levels of luteinizing hormone.
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Normal or increased levels of estradiol.
Although not everyone with androgen insensitivity syndrome (especially partial androgen insensitivity syndrome) will have an androgen receptor mutation, the diagnosis of androgen insensitivity syndrome is confirmed if androgen receptor gene sequencing reveals a mutation.
What Are the Treatment Modalities for Androgen Insensitivity Syndrome?
Treatment for Primary Symptoms:
For complete androgen insensitivity syndrome, treatment options include:
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Prepubertal gonadectomy combined with estrogen replacement therapy.
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Removal of the testes after puberty when feminization is complete.
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Gonadectomy is becoming increasingly contentious because the risk of cancer is so low.
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To prevent dyspareunia, vaginal dilatation may be used as an additional complete androgen insensitivity syndrome treatment.
Similar to the therapy for complete androgen insensitivity syndrome, prepubertal gonadectomy is more frequently used to treat partial androgen insensitivity syndrome in those whose genitalia are primarily female. This is done to help prevent the development of clitoromegaly throughout puberty. The tendency has been for parents and medical personnel to designate the sex of rearing following the conclusion of an expert review.
In cases of partial androgen insensitivity syndrome, patients with ambiguous or mostly male genitalia.
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Partial androgen insensitivity syndrome patients born as men may have urologic procedures such as orchiopexy and hypospadias correction.
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If gonadectomy is performed after puberty and the partial androgen insensitivity syndrome patient is treated as a girl, combined estrogen and androgen replacement medication may be necessary.
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Pharmacotherapy with androgens may be used to help with infant testicular atrophy.
The affected person and family should be informed of the androgen insensitivity syndrome diagnosis in a compassionate setting with professional and familial support.
Treatment for Secondary symptoms:
The best way to maintain bone health is by:
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Regular weight-bearing activities.
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Calcium supplements.
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Vitamin D supplements.
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Bisphosphonate medication may be necessary for patients with multiple fractures or signs of decreasing bone mineral density.
Conclusion
Androgen insensitivity syndrome is characterized by a feminine phenotype in a person with an XY karyotype and testes that produce testosterone levels that are age-appropriately normal. Mutations in the X-linked androgen receptor gene, which codes for the ligand-activated androgen receptor, a transcription factor and part of the nuclear receptor superfamily, lead to pathogenesis. The management of androgen insensitivity syndrome should be carried out by a multidisciplinary team and include gonadectomy to prevent gonad tumors in later life, and adequate sex-hormone replacement therapy during puberty and beyond is the line of treatment.
