Pediatric androgen insensitivity syndrome (AIS)

What is pediatric androgen insensitivity syndrome (AIS)?

Androgen insensitivity syndrome is an example of disorders of sex development (DSD). An androgen is a hormone that causes a male child to develop male characteristics. Testosterone is the most well known androgen and is made by the testes (and also in smaller amounts in the ovaries and adrenal glands of females).

What are the different types of pediatric androgen insensitivity syndrome (AIS)?

There are two general types of androgen insensitivity syndromes: 

Complete androgen insensitivity syndrome (CAIS)

CAIS is a syndrome where the body is completely resistant to the effects of androgens. When these children are born, they generally appear to be normal females and often the diagnosis is not suspected. The complete form of the syndrome is rare and occurs in about 1 in 20,000 live births.

These patients have male chromosomes (46XY), but because androgens have no effect they develop normal female external genitalia. Internally these patients have gonads that are testes but reside inside the abdomen and the upper part of the vagina, uterus, and fallopian tubes are absent.   

These children most commonly present in one of two ways:

• An inguinal hernia before puberty

• Failure to start menstruation (periods) with puberty

• Failure to develop pubic hair despite normal breast development

These children do go through puberty with breast development because their androgens are converted to a hormone (estrogen) that causes breast development. 

Once the diagnosis of CAIS is made families and patients typically have a lot of questions and concerns. It can come as quite a surprise because these patients appear to be completely normal females. 

Generally, these patients do not have any other health problems. They typically have a female gender identity. Unfortunately, pregnancy is not possible due to the absence of uterus. 

While it is somewhat controversial, some specialists may offer removal of the gonads after puberty because of a slightly increased risk of gonad tumors. If the gonads are removed, estrogen replacement therapy is needed. Occasionally, but not always, the vagina is too short. Serial dilation, taught in the office is the most successful and preferred method for vaginal creation. Rarely, is surgery needed. 

Partial androgen insensitivity syndrome (PAIS)

(PAIS) is another form of androgen insensitivity. As the name suggests, PAIS patients are only partially sensitive to androgens.  

Externally, the patients have ambiguous genitalia ranging from mostly female to almost completely normal male. Internally, the patients do not have a uterus or fallopian tubes. The testes can be in the abdomen, in the groin, or completely descended. These patients typically present soon after birth due to the ambiguous genitalia. 

The diagnosis of PAIS is sometimes difficult to make and the management of patients with PAIS can be challenging. Because there is a variable amount of male hormone exposure in the brain, it is difficult to predict with certainty male or female gender identity.

If a patient is raised male, they may require reconstructive surgery and may have dissatisfaction with final penile size and function in the future. In addition, due to the conversion of androgens to estrogens males may have breast development that may require surgical management. 

If a patient is raised female, they may also require some type of reconstructive surgery.

What are the signs and symptoms of pediatric androgen insensitivity syndrome (AIS)?

Symptoms may not be noted until puberty and may include:

• A short vagina (blind pouch), but no cervix or uterus (found upon pelvic exam/ultrasound)

• No menstrual cycle, due to an absent uterus

• Normal breast development with little or no pubic and armpit hair

• No acne during puberty

• Hernias or lumps in the groin or abdomen (which are actually testes)

• An inguinal hernia with testes that can be felt during a physical examination

• Testes in the abdomen 

• External genitals that aren't clearly male or female (ambiguous genitalia), in the case of partial or incomplete androgen insensitivity

How is pediatric androgen insensitivity syndrome (AIS) diagnosed?

Complete androgen insensitivity is typically discovered at puberty, when a girl fails to start having periods or doesn’t develop pubic or underarm hair. Occasionally, a child is diagnosed when a growth is felt in the abdomen and determined to be a testicle during surgery.

Diagnosis starts with a thorough medical history and physical exam, including a pelvic exam.

Additional testing may include:

• Blood test – to check hormone levels

• Genetic testing (karyotype)

• Pelvic ultrasound or MRI of the pelvis to see the internal organs, confirming the absence of internal female reproductive organs

Partial androgen insensitivity is usually discovered when the baby is born because the external genitals aren't clearly male or female (ambiguous genitalia).

How is pediatric androgen insensitivity syndrome (AIS) treated?

The testicles most often are not removed until a child finishes growing and goes through puberty. They sometimes are removed because they can develop cancer, just like any undescended testicle. The risk of cancer is very low, however, and some individuals may choose to monitor over time with serial imaging, rather than undergo surgery.

• If the gonads are removed for complete or partial androgen insensitivity, your child’s doctor will prescribe estrogen replacement at or after puberty, to prevent menopausal symptoms and osteoporosis.

After puberty, some patients use vaginal dilators over 3 to 6 months (or undergo surgery) to lengthen the vagina.

Treatment and gender assignment can be a very complex issue, and must be targeted to each individual person. Your doctor can recommend counseling and psychological support for your child and your family.