Androgen Insensitivity Syndrome

Definition

Definition of Androgen Insensitivity Syndrome
Androgen insensitivity syndrome (AIS) is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is only clinically significant when it occurs in genetic males (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene). Clinical phenotypes in these individuals ranges from a normal male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome.

Symptoms

Symptoms of Androgen Insensitivity Syndrome
AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

Causes

Causes of Androgen Insensitivity Syndrome
Androgen insensitivity syndrome (AIS) is caused by various genetic defects on the X chromosome that make the body unable to respond to the hormones responsible for the male appearance.

The syndrome is divided into two main categories:

1. Complete AIS
2. Incomplete AIS

Complete androgen insensitivity prevents the development of the penis and other male body parts. The child born appears to be a girl. The complete form of the syndrome occurs in as many as 1 in 20,000 live births.

The degree of sexual ambiguity varies widely in persons with incomplete AIS. Incomplete AIS can include other disorders such as Reifenstein syndrome (also known as Gilbert-Dreyfus syndrome or Lubs syndrome), which is associated with breast development in men, failure of one or both testes to descend into the scrotum after birth, and hypospadias, a condition where the opening of the urethra is on the underside, rather than at the tip, of the penis.

Diagnosis

Diagnosis of Androgen Insensitivity Syndrome
Complete AIS is rarely discovered during childhood, unless a mass is felt in the abdomen or groin that turns out to be a testicle when it is explored surgically. Most people with this condition are not diagnosed until they fail to menstruate or have difficulties becoming pregnant.

Incomplete AIS, however, is often discovered during childhood because the person may have both male and female physical characteristics.

Tests used to diagnose this condition may include:

1. Blood work to check levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)
2. Genetic testing (karyotyping)
3. Pelvic ultrasound

Treatment

Treatment of Androgen Insensitivity Syndrome
Unusually located testicular tissue may not be removed until a child completes puberty and growth is complete. At this time, the testis may be removed because they can develop cancer like any undescended testicle.

Prognosis

Prognosis of Androgen Insensitivity Syndrome
The outlook for complete AIS is good if at-risk testicular tissue is removed at the proper time. The outlook for incomplete AIS depends on the presence and severity of ambiguous genitalia.

Prevention

Prevention of Androgen Insensitivity Syndrome
Complications include testicular cancer, infertility, and complex psychosocial issues.