Contents
Androgen insensitivity (testicular feminization) syndrome (AIS) is a rare spectrum of defects in androgen action characterized by evidence of feminization (i.e., under-masculinization) of external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype.
Also known as Reifenstein syndrome, Rose-water syndrome, Morris’ syndrome, Gilbert-Dreyfus syndrome, Goldberg-Maxwell syndrome, Lubs syndrome, Aiman’s syndrome.
- X-linked recessive inheritance
Embryology
During embryological development the internal genitalia consist of 2 accessory ducts; the mesonephric duct (Wolffian duct) and the para-mesonephric duct (Mullerian duct). The mesonephric duct is the precursor to male genitalia and its development. Under the influence of SRY gene located on Y-chromosome (Yp11), in the 7th week of fetal development, the testes begin their differentiation. Three key hormones responsible for male external and internal genital development are anti-mullerian hormone (AMH), testosterone and dihydro-testosterone are secreted by the testes. The anti-mullerian hormone causes para-mesonephric duct to regress while testosterone influences the growth of male accessory structures i.e, penis, vas deferens, epididymis, seminal vesicle.

Androgen insensitivity syndrome is the result of profound resistance of the androgen receptor towards the action of androgen.

Clinical features
Commonly diagnosed at puberty when the patient presents with primary amenorrhea.
Complete AIS (CAIS):
Typical female external genitalia
- Absent/rudimentary mullerian structures: Uterus, fallopian tube, cervix and a blind ended short vagina
- 2 non-dysplastic, undescended testes
- Absence/scanty pubic & axillary hair
- Normal/underdeveloped breast
Partial AIS (PAIS):
PAIS results in a varied phenotype from the residual androgen receptor function. Symptoms vary from severe under-masculinization with female genitalia to male genitalia.
- PAIS with predominantly female external genitalia: Presents in a manner similar to CAIS with signs of external genital masculinization
- Clitoromegaly
- Posterior labial fusion
Reifenstein syndrome:
PAIS with ambiguous genitalia/predominantly male genitalia
- Hypospadias
- Bifid scrotum
- Micropenis
Mild AIS (MAIS):
Typical male external genitalia
- Normal male phenotype with isolated micropenis
- Adulthood: Gynecomastia and infertility
Diagnosis
The diagnosis of CAIS and PAIS includes assessing clinical and biochemical features, 46 XY karyotype, and exclusion of defects in testosterone synthesis. Furthermore, confirmation is possible with genetic testing.
Exclusion of defects in testosterone synthesis:
- Levels of testosterone, LH, and FSH (1st year of life)
- Sertoli cell function: Normal/elevated levels of Inhibin B or AMH
- hCG stimulation test with measurement of serum androstenedione, testosterone, and DHT 72 hours afterward
- Basal hormone measurements (adults)

Differential diagnosis:
- Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: Phenotypic females with amenorrhea and partial/complete absence of the cervix, uterus, and vagina
- Hypospadias
Management
Management of androgen insensitivity syndrome involves a holistic approach towards the psychological, physiological, social well being of the individual suffering from this disorder.