Ambiguous Genitalia

Sometimes when a baby is born, the external genitalia do not look typically male or female. At other times, the genitalia look typical, but do not match the baby’s expected gender based on chromosome information, for example, parents were expecting a boy based on amniocentisis, but their baby’s genitalia appear more female. In these cases, the baby is said to have ambiguous genitalia, conditions that fall under the umbrella diagnosis of Disorders of Sex Development (DSD).

What is typical genital development?

Early in fetal development, the tissue that will become the gonads (ovaries or testes) is undifferentiated and has the potential to become either ovaries or testes. Gonadal development is the result of a complex interaction between chromosomes and hormones. Humans have 46 chromosomes in each cell of their bodies, or 23 pairs. The 23rd pair determines our gender; females usually have two X chromosomes, while males usually have one X and one Y chromosome. The chromosome complement (karyotype) in humans is written: 46 XX for a female or 46 XY for a male.
There is a gene located on the short arm (top half) of the Y chromosome, called "SRY," which, if present, will cause the undifferentiated gonad to become testes (indicating a male) around the sixth week of fetal life. At the same time, shrinkage of what would have been the female reproductive tract occurs. As the testes produce testosterone, the phallus (penis), scrotum and urethra form. Later, during the seventh to eighth month of the pregnancy, the testes will descend into the scrotum.
If there is no SRY gene, the gonad will usually differentiate into an ovary (indicating a female). Likewise, the female reproductive tract will continue to develop, forming the uterus and fallopian tubes. At the same time, shrinkage of what would have become the male reproductive organs occurs.

What are ambiguous genitalia?

A variety of genetic, hormonal, and environmental factors may influence development, leading to ambiguous genitalia. Ambiguous genitalia, as the word implies, may make determining the child's gender more difficult. Very few infants with ambiguous genitalia have genitals that are so ambiguous that a gender determination is not able to be made at birth or shortly thereafter. Far more common are the following observations at birth:

A girl with masculinization who appears to have a small penis (due to the overproduction of male hormones)
A boy with an abnormally small penis that resembles a female clitoris (due to an insensitivity to male hormones or failure to produce male hormones)

There is great variability in how the genitals may appear.

What causes ambiguous genitalia?

There are a number of different causes of ambiguous genitalia, with the most common described below. The cause, in many cases, is not known and the disorder appears to occur by chance. Children who are born with ambiguous genitalia may fall into one of the following groups:

46 XX – children who have:

Normal female internal structures (uterus, ovaries, fallopian tubes), but masculinized external genitalia. The most common cause of 46 XX DSD is Congenital Adrenal Hyperplasia (CAH). CAH is a serious medical condition which can be associated with severe electrolyte (such as sodium) imbalances.

46 XX DSD can also result from exposure of the fetus to high levels of male hormones while in utero. This can occur if hormones enter the placenta, such as when the mother receives progesterone to prevent a miscarriage or has a hormone-producing tumor.

46 XY DSD – children with a 46 XY karyotype and one of the following conditions:

Testes with normal female external genitalia. This is called Androgen Insensitivity Syndrome because the baby is not responsive to androgens (testosterone)
Testes with ambiguous genitalia. This may be caused by a condition called 5-alpha-reductase deficiency. The enzyme 5-alpha reductase is deficient; therefore, it cannot carry out its task of converting testosterone into dihydrotestosterone (DHT), which is necessary for complete masculinization of a male fetus

Ovotesticular DSD – children who have:

Both ovarian and testicular tissue
External genitalia that are partially ambiguous
Chromosomes that are either 46 XX, 46 XY, or a mixture (referred to as "mosaic") of the two (46XX/46XY)

Gonadal dysgenesis - children who have:

An undeveloped gonad
Internal sex organs that are usually female
External genitals that may vary between normal female and normal male, with the majority female
Chromosomes that are 45 X, 46 XY, 46 XX, or a mosaic (such as 45X/46XX)

How is the gender determined in a child with ambiguous genitalia?

When a child's genitalia appear ambiguous at birth, your child's physician will conduct a medical history and a physical examination of your child's external genitalia. The medical history will include the mother's health during pregnancy and a family history of any neonatal deaths or genital abnormalities. First, your child's physician will make a diagnosis of the underlying cause of the disorder. Diagnostic procedures may include a newborn screening test for CAH, hormonal studies and a biopsy of the reproductive organs.
To identify the baby’s gender, your child's physicians will consider the following:

A pelvic ultrasound to check for the presence of female reproductive organs
A genitourethrogram to look at the urethra and vagina if present
A chromosomal analysis to help determine genetic sex: 46 XX or 46 XY
Fertility potential
Ability of an internal reproductive organ to produce appropriate sex hormones for the gender of rearing
Risk of future health conditions (i.e., cancer) that may develop in the original reproductive organs later in life
The actions of male or female hormones on the fetal brain
The family’s opinion

Our approach to treating ambiguous genitalia

Sometimes there is an increased risk for tumors in the gonads. Treatment for ambiguous genitalia depends of the type of the disorder, but will usually include corrective surgery to remove or create reproductive organs appropriate for the gender of the child. Treatment may also include hormone replacement therapy (HRT). Treatment is decided on a case-by-case basis through discussions with the family. Our team of providers will help each family decide what makes the most sense for their child.
Reviewed by: Aileen P. Schast, PhD

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Endocrine Diseases

Endocrine Diseases: MedlinePlus

Your endocrine system includes eight major glands throughout your body. These glands make hormones. Hormones are chemical messengers. They travel through your bloodstream to tissues or organs. Hormones work slowly and affect body processes from head to toe. These include

Growth and development
Metabolism - digestion, elimination, breathing, blood circulation and maintaining body temperature
Sexual function
Reproduction
Mood

If your hormone levels are too high or too low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond to hormones the way it is supposed to. Stress, infection and changes in your blood's fluid and electrolyte balance can also influence hormone levels.
In the United States, the most common endocrine disease is diabetes. There are many others. They are usually treated by controlling how much hormone your body makes. Hormone supplements can help if the problem is too little of a hormone.