Complete Androgen Insensitivity Syndrome

An inherited disorder caused by androgen insensitivity with affected males having a female phenotype with normal female external genitalia but abnormal or absent internal female organs. Testes are often intraabdominal, in the inguina, or in the labia. Normal male (46,XY) karyotype.

Testicular Feminization; Androgen Receptor Deficiency; Dihydrotestosterone Receptor Deficiency; Male Pseudohermaphroditism as a Result of Androgen Insensitivity; Hairless Women Syndrome.

Estimates vary from 1:7,000-20,000 male live births. No racial predilection has been reported.

X-linked recessive with the responsible gene encoding for the androgen receptor being located on Xq11-q12. More than 200 different mutations have been described.

The basic etiology of androgen insensitivity syndrome (AIS) is a mutation in the androgen receptor gene that results in the gene's loss of function. The functional defects can range from complete absence of receptors on the cell surface to decreased substrate binding affinity with loss of signal transmission. Despite normal or elevated levels of androgen, functional loss of the androgen receptor is clinically equivalent to a lack of androgen and results in prenatal undervirilization of external genitalia, and absence of pubic and axillary hair, lack of acne, and absence of voice changes at puberty. Leydig cell stimulation to estrogen production occurs probably because of a failure in feedback repression of the pituitary gland, which shares the unresponsiveness to androgen. Peripheral conversion of testosterone and androstenedione to estradiol finally results in elevated estrogen serum levels. This on the one hand explains the absence of (androgen mediated) axillary and pubic hair, acne, and voice changes and on the other hand the development of normal breasts in these patients.

The clinical findings of inguinal hernia with a labial mass in infancy and primary amenorrhea despite typical female secondary sex characteristics, but scant or absent pubic and axillary hair in puberty should raise suspicion for AIS. Affected males have female external genitalia associated with normal or high testosterone serum levels. In infancy, plasma luteinizing hormone (LH) and testosterone levels and the response to luteinizing hormone-releasing hormone (LHRH) are higher than in age-matched controls. In puberty, the androgen insensitivity, which also affects the hypothalamic-pituitary area, results in elevated testicular androgen and estradiol synthesis.

These genotypic male patients are phenotypic females. Anatomically, they have normal female external genitalia but a blind-ending vaginal pouch and absent uterus and fallopian tubes. The testes usually are located intraabdominally, in the inguinal canal, or in the labia. Leydig cells appear hyperplastic and form adenomatous clumps. Primary amenorrhea and scant pubic and axillary hair contrast with well developed female personality and body shape (including breasts). Patients often appear tall for females, and the clinical signs result from high estrogen levels. Other features include inguinal hernia and an increased risk of testicular malignancies (Sertoli cell adenomas, seminomas, malignant sex-cord stromal tumor) after 25 years of age. Patients often present for orchiectomy and vaginal lengthening procedures, both now often done at the end of the second or at the beginning of the third decade of life so that the patient is mature enough to participate actively in the treatment decisions. Patients are mentally absolutely normal. Gender identity is that of a normal female.

Bear in mind that some patients may not know the exact details of their genetic status, anatomy, or endocrinology.

The larynx may be smaller and the trachea shorter than expected. Otherwise no specific anesthetic consideration should arise from this disorder.

An increased tolerance to steroidal neuromuscular blocking agents has been described. After orchiectomy, hormone replacement therapy with estrogens is standard for patients with AIS.

Reifenstein Syndrome: A condition characterized by partial androgen receptor deficiency resulting in hypogonadism or male pseudohermaphroditism.

Mayer-von Rokitansky-Küster-Hauser Syndrome: A syndrome characterized by congenital absence of the vagina, rudimentary cornua uteri, and morphologically normal ovaries and fallopian tubes situated on the pelvic sidewall. Primary amenorrhea with normal ovulation, breast development, body, and hair. Affected women are infertile. Frequently associated with urinary tract anomalies, skeletal abnormalities, congenital heart conditions, and inguinal hernia.