An 18-year-old girl has presented with testicular feminization syndrome, testis at the labia, and presence of gonads in the peritoneal cavity. The plan of treatment is to remove the testicular tissue and to biopsy the intraperitoneal gonads through laparoscopic approach along with creating a neovagina. Do you have any suggestions with regard to treatment?
Response from Scott G Chudnoff, MD
Previously referred to as testicular feminization, this condition is known as complete androgen insensitivity syndrome. It is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors. The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.
There are 2 primary components in the management of these patients: surgical and psychological. The psychological component is critical for these patients to have normal lives and to not feel stigmatized or deficient. The term "gonad" rather than "testis" should be used to help engender a sense of femininity. It is also recommended when initially presenting the diagnosis to explain that there is an abnormality in the sex chromosomes rather than just saying that she has a Y chromosome, as the general population associates this with maleness. Continuous counseling should occur from the time of diagnosis throughout adolescence and adulthood, with the goal of reassuring these patients that although they will be unable to conceive, they are able to live a complete and robust life as a female. It is inappropriate today to withhold information regarding the disease from the patient, but rather the patient should be gradually educated regarding the disease as she develops the mental capacity to understand the various aspects.
The second primary aspect in their management revolves around surgical treatment of the condition. The testis may be located anywhere from the abdominal cavity, along the inguinal canal, to the labia majora. Given that the testis in these patients has an extremely high risk of malignant transformation into gonadoblastomas or dysgerminomas (approximately 20%), it is critical to remove the testis in these patients prophylactically. Given that the risk of cancer developing before 20 years of age is very low and that the testis is producing necessary hormones for breast development and epiphyseal closure, it is recommended that gonadectomy be performed after they have completed pubertal development at approximately 18 years of age. Typically, this can be performed via laparoscopy for the testis in the abdominal cavity or inguinal canal.
Another major physical aspect that requires attention is the shortened or absent vagina in these patients. The majority of these patients will be unable to engage in sexual intercourse with these abnormalities. There are two possible treatment modalities to correct this: vaginal dilators and surgical creation of a neovagina. In general, the recommendation is to first try vaginal dilators, even in cases of an absent vagina. Typically, with regular, slow, persistent vaginal dilation, a vagina can be created in the vast majority of these patients that will be penile receptive.
In a minority of patients, surgical creation of a neovagina will be necessary. The McIndoe surgical procedure for vaginal agenesis is the most well known. A space is dissected between the rectum and the bladder, and a split-thickness skin graft from the buttocks is used to form the vagina; a specially crafted dilator placed at the time of the procedure creates continuous dilation of the vagina while the graft heals. Other procedures include Williams vulvovaginoplasty, musculocutaneous flaps, and free intestinal grafts. The decision of which approach to take is dictated by the patient's characteristics and needs.
In this patient, it may be prudent to remove both of the gonads and not just biopsy one. Although the risk of developing malignancy is presently low for her, it will steadily increase as she ages. It is necessary to give supplemental estrogen after the gonadectomy; given the absence of a uterus, there is little reason to support giving progesterone. If the decision is to leave the gonad in situ, then, at the very least, high-resolution imaging should take place yearly to evaluate any changes.
With regard to the creation of a neovagina, I would strongly recommend giving vaginal dilation a chance given the low associated morbidity and high success rates. Also, there are potentially many complications associated with the surgical neovaginal route, including breakdown or rejection of the graft, infection, and damage to the surrounding tissue. If the patient has already failed vaginal dilators, then the McIndoe approach would probably be a good first-line method for surgical treatment.
Medscape Ob/Gyn. 2005;10(2) © 2005 Medscape
Cite this: Scott G Chudnoff. Complete Androgen Insensitivity Syndrome - Medscape - Nov 29, 2005.