|Year : 2003 | Volume
| Issue : 2 | Page : 145-151
Surgical management of ambiguous genitalia in infants and children: An SGPGI experience
Subodh Kumar Das, Anant Kumar, NK Arvind, S Phadke
Department of Urology and Renal Transplanation and Department of Medicine Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014
| Abstract|| |
Introduction: Assignment of a proper gender to a neonate born with ambiguous genitalia is a social emergency. Once a sex has been assigned the next critical step is performance, if needed, of a reconstructive procedure in a timely fashion. In an attempt to evaluate our experience with this unique group of patients, we have retrospectively reviewed the course of 31 children managed surgically at our institute between 1989 and 2000.
Patients and Methods: This series consists of 16 genotype females with congenital adrenal hyperplasia (CAH), 7 male pseudohermaphrodites, 5 children with mixed gonadal dysgenesis (MGD), and 3 true hermaphrodites. All the 16 patients with CAH underwent vaginoplasty, and clitoral recession. Five of the male pseudohermaphrodites were raised as females. All of them underwent B/L gonadectomy, and clitoral recession. Perineal vaginoplasty was done in 4 of these patients and I patient who was due for colo-vaginoplasty was lost to follow-up. 2 male pseudohermaphrodites were raised as males. Both of them underwent B/L orchiopexy and hypospadias repair. Four of the 5 cases of MGD were given a female sex assignment and all 4 underwent gonadectomy due to high risk of gonadoblastoma. In the 5th patient a male gender assignment was given. There were 3 true hermaphrodites, 2 of whom were managed by clitoral recession and vaginoplasty. One patient was diagnosed at the age of 15 years. This patient had been brought up as a male child and presented to us with the complaint of pain in the lower abdomen. Investigations revealed haematometra and haematocolpos and the patient had to undergo B/L salpingo-oophorectomy and hysterectomy.
Results: The postoperative period in most of the patients was uneventful except for 2 minor complications. The cosmetic results have been excellent. 2 patients were lost to follow-up. Follow-up in the rest of the patients ranged from 9 months to 6.3 years and all the patients were found well adjusted to the society as far as their gender assignment is concerned. However the functional results are yet to be evaluated, as most of the patients have not yet achieved full sexual maturity.
Conclusion: This retrospective review emphasizes the complexities of assessment and management of ambiguous genitalia in infants and children. It also confirms the data from other series that the vast majority of infants born with the 4 most common forms of ambiguous genitalia (CAH, MGD, male pseudohermaphroditism, and true hermaphroditism) may be raised as females as phallic inadequacy usually makes it difficult to achieve a cosmetically acceptable appearance. However the sex of rearing and parents' intentions and wishes should be taken into consideration in the reconstruction of genitalia of a child.
Keywords: Ambiguous genitalia, surgery.
|How to cite this article:|
Das SK, Kumar A, Arvind N K, Phadke S. Surgical management of ambiguous genitalia in infants and children: An SGPGI experience. Indian J Urol 2003;19:145-51
|How to cite this URL:|
Das SK, Kumar A, Arvind N K, Phadke S. Surgical management of ambiguous genitalia in infants and children: An SGPGI experience. Indian J Urol [serial online] 2003 [cited 2013 May 25];19:145-51. Available from: http://www.indianjurol.com/text.asp?2003/19/2/145/37147
| Introduction|| |
An infant born with ambiguous genitalia is a potential social and medical emergency. It needs a rapid and organized evaluation to assign a proper gender, identify a possible life-threatening condition and begin necessary medical, surgical and psychological intervention. During the past 11 years we have come across 31 such patients with ambiguous genitalia who required surgical intervention. These patients represent only a subgroup of infants and children with abnormalities of sexual differentiation seen at our institution. On the other hand, a large majority of these patients did not undergo any surgical intervention and were lost to follow-up.
| Patients and Methods|| |
A retrospective review of all patients with ambiguous genitalia managed surgically at this institute between December 1989 and December 2000 was carried out. The cases were categorized into following subgroups: congenital adrenal hyperplasia (CAH: 16), male pseudohermaphroditism (7), mixed gonadal dysgenesis (MGD: 5), and true hermaphrodites (3). Diagnostic workup included chromosomal analysis, blood and urinary steroid measurements, abdominal and pelvic ultrasound, as well as retrograde genitogram. The genitogram was performed in the X-ray suite with insertion of a Foley catheter into the very distal part of the common perineal opening low-pressure injection of a water-soluble contrast agent and, was performed with careful and repeated fluoroscopy in order to identify the perineal internal anatomy. Cystoscopy and laparoscopy were done just before the surgery to confirm the findings.
Congenital adrenal hyperplasia:
The total number of patients with congenital adrenal hyperplasia was 16. The age at diagnosis ranged from newborn to 4 years and the age at operation ranged from 3 months to 4 years [Table - 1]. All of the patients were genetic females. 14 patients underwent perineal vaginoplasty and 2 underwent vaginal pull through. All these 16 patients underwent recession clitoroplasty [Figure - 1] and [Table - 2].
7 patients received the diagnosis of male pseudohermaphroditism in this series. The most common form of this entity is called the testicular feminizing syndrome (TFS). The age at diagnosis ranged from 3 months to 14.5 years [Table - 3]. By definition the karyotype in each case was 46, XY. 5 of these patients were raised as females and 2 were raised as males. All 5 who were raised as females underwent B/L gonadectomy and clitoral recession. 4 of these patients underwent perineal vaginoplasty. 2 patients underwent simultaneous introitoplasty [Figure - 2]. The 5th patient had a high confluence of vagina and urogenital sinus at the area of urinary sphincter. For vaginal reconstruction a colovaginoplasty had been planned for this patient at a later date. However this patient did not come back in follow-up. 2 patients with male pseudohermaphroditism were raised as males. One of them was operated at the age of 3 years. This patient had a perineoscrotal hypospadias and bilateral testes in the inguinal region. Diagnostic laparoscopy revealed no mullerian structures. The patient underwent B/L orchiopexy and penile reconstruction stage 1 (Bayer's flap) initially, and subsequently Johanson's hypospadias repair and glanuloplasty. In the other patient with male pseudohermaphroditism the age of operation was 3 months. This patient underwent similar procedures as the former patient. Along with that, herniorrhaphy for right inguinal hernia was also done in this patient.
Mixed gonadal dysgenesis:
There were 5 patients with mixed gonadal dysgenesis (MGD). The age at diagnosis ranged from l month to 8 years [Table - 4]. Chromosomal analysis most commonly revealed 45, X/46, XY composition. Four patients were raised as females. All the 4 patients underwent B/L gonadectomy and perineal vaginoplasty and recession clitoroplasty. In the 5th patient a female gender was recommended, however the parents refused it. This patient underwent excision of mullerian structures (uterus, ovaries, Fallopian tube More Detailss and vagina). Reconstruction of penoscrotal hypospadias was done using dartos based tabularized preputial flap.
True hermaphroditism represents the least common form of ambiguous genitalia; there were 3 children in this series [Table - 5]. 1 patient was 1-month old and the other was 9month old at the time of diagnosis. Chromosomal analysis in both the cases was 46. XX/XY mosaic. Both the patients underwent B/L gonadectomy, clitoral recession and perineal vaginoplasty. The 3rd patient in this group was diagnosed at the age of 15. This patient had been raised as a male and presented to us with the complaints of breast enlargement and suprapubic pain for 2 years. The patient also complained of having a short phallus. Clinical examination revealed the presence of a tender suprapubic lump. Patient had a short phallus of approximately 1.8 cm length. CECT revealed the presence of haematocolpos and haematometra. The patient underwent exploratory laparotomy, hysterectomy and B/L salpingo-ophorectomy.
| Results|| |
In the 16 patients with congenital adrenal hyperplasia, the mean age at diagnosis was 1.9 years (new born - 4 years). The mean age of operation was 2.2 years (range 9 months to 4 years). The postoperative period was uneventful and free of any complication in all the patients except for I patient whose clitoris sloughed off after recession cliteroplasty. Mean follow-up was 4.6 years (range 1.1 years to 7.9 years).
In the 7 patients with male pseudohermaphroditism, the mean age of diagnosis was 25.3 months (3 months to 14.5 years). The mean age of surgery was 47 months (3 months to 14.5 years). The patient who underwent Johanson's hypospadias repair and glanuloplasty developed urethrocutaneous fistula in the postoperative period, which needed repair. No other patient had any immediate or late postoperative complication [Figure - 3],[Figure - 4]. One patient was lost to follow-up. The mean follow-up of the rest of the patients was 2.4 years (range 9 months to 4 years).
In the mixed gonadal dysgenesis group the mean age at diagnosis was 2.1 years (range 1 month to 8 years). The mean age of operation was 2.2 years (range I month to 8 years). None of these patients had any immediate or late postoperative complication. The mean duration of followup in this group of patients was 3.9 years (range 1 year to 6.3 years).
Out of the 3 patients with true hermaphroditism I patient who was diagnosed at the age of 15 years was lost to follow-up after surgery. In the other 2 patients, the mean age at diagnosis was 5 months (range 1 to 9 months). The mean age at surgery was 6.5 months (range 3 to 12 months). Both the patients had an uneventful recovery in the postoperative period. The mean follow-up was 3.5 years (range 3 to 4 years).
Cosmetic results in all the patients have been excellent. However the functional evaluation is still awaited, as most of the patients have yet not achieved full sexual maturity.
| Discussion|| |
Early diagnosis and prompt gender assignment is essential in the satisfactory management of children born with ambiguous genitalia. This bears obvious long-term effects on the well being of both the child and parents. Delay in proper sex assignment results in severe emotional disability and even sexual abuse at times. In general female gender assignment is made much more commonly because surgical reconstruction is far more successful. The only exception to this is the genetic male with severe penoscrotal hypospadias and bilateral undescended testes, who is usually raised as a male child. It is uniformly agreed that an inadequate phallus is difficult to correct surgically and that the patient will fare much better in the female gender role.
The 4 major pathological groups of patients with ambiguous genitalia are congenital adrenal hyperplasia, male pseudohermaphroditism, mixed gonadal dysgenesis, and true hermaphroditism. Children born with these syndromes are generally raised as females because the phallus is usually inadequate for assumption of the male gender role. Infants born with congenital adrenal hyperplasia are genetic females who have been exposed to excessive levels of exogenous androgens. There are 3 enzymatic deficiencies, which are most commonly associated with this syndrome, namely 21-hydroxylase, 11-hydroxylase, and 3-beta-hydroxysteroid dehydrogenase. All these enzyme deficiencies result in overproduction of androgenic intermediary metabolites that masculine the external genitalia of females. The phenotype picture varies from mild clitoral enlargement alone to complete masculinization of urethra with a normal appearing male penis and the urethral meatus at the tip of the penis. This later clinical picture is associated with complete fusion of labia. These patients require lifetime replacement with glucocorticoids and mineralocorticoids if they represent the salt loosing form of CAH. The ideal surgical management is a cut-back or flap vaginoplasty together with a clitoral recession at 3 to 6 months of age.
Male pseudohermaphroditism occurs in genetic males (46, XY) with deficient masculinization of the external genitalia. The most common form of this entity is known as the testicular feminizing syndrome. Male pseudohermaphroditism can be due to the following: (1) inadequate testosterone production due to deficiencies of the enzymes necessary for its biosynthesis; (2) inability of the external genitalia target organs to convert testosterone to dihydrotestosterone due to 5-alpha-reductase deficiency; and (3) deficiencies in androgen receptors. Sex assignment should be extremely individualized in these cases. Most of these patients are usually raised as females as the phallus is inadequate for the male gender role.  If female gender is chosen, gonadectomy is delayed until puberty unless the testes are palpable in the hernial sac, groin or in the labia. Estrogen supplementation after gonadectomy is indicated. Most of these patients can be managed with a perineal vaginoplasty; however, a few require vaginal replacement. We prefer the use of colon for this operation. In those cases, who are raised as males we recommend an early surgical reconstruction of the external genitalia.
The syndrome of mixed gonadal dysgenesis is associated with dysgenetic gonads and retained mullerian structures. There is a a very high incidence of malignant tumor development in the dysgenetic gonads (50%). Gonadoblastoma is the most commonly seen tumor; however, seminoma and dysgerminoma can occur, especially in the streak gonads.  For these reasons, we recommended B/L gonadectomy in all patients with mixed gonadal dysgenesis. Surgical reconstruction is same as CAH in that all these patients should be reared as females and undergo appropriate reconstruction of the external genitalia.
True hermaphrodites represent the rarest form of ambiguous genitalia. These patients have both normal male and female gonadal tissue with an ovary on 1 side and a testis on the other or an ovotestis on 1 or both sides. 80% of these patients have a 46, XX karyotype. Most of these children have an inadequate phallus and should be raised as females. In these cases, the testis should be removed and the testicular portion of the ovotestis should be removed, leaving the ovarian portion in place.  Surgical reconstruction is similar to that used for the child with CAH and MGD. If the phallus is adequate for the male gender role, then all ovarian and mullerian structures are removed and hypospadias repair is carried out.
The timing of surgery is judged keeping in view a balance between the psychological advantages of early surgery and the technical limitations imposed by the small size of the structures. Canty reporting his series of 18 patients with several forms of ambiguous genitalia suggested 2.5 to 3 years of age as the optimal time for reconstruction.  In contrast, Sharp et al, in their series presented 9 infants with various forms of ambiguous genitalia, all of whom were operated at an age of less than 6 weeks.  Donohoe and Hendren also favor early reconstruction, suggesting that 3 to 6 months of age may be the optimal time.  However, they feel that children with high insertion of the vagina into the urinary tract should be operated at an older age (around 2 yrs).
Determination of the exact location of the insertion of the vagina into the urogenital sinus or urethra is best done with retrograde genitogram as well as endoscopy at the time of initial surgery. Perineal vaginoplasty can be performed in the newborn period if the communication between the vagina and the urethra is distal to the external sphincter of the urethra. If the communication is at or proximal to the sphincter, then we feel that a vaginal pull through is the more appropriate operation.
The importance of the clitoris for orgasm and normal sexual function has been emphasized by Nihoul et al  and Randolph et al  in their series and they recommend preservation of all or part of the clitoris with its nerve supply. In our series clitoris was recessed underneath the pubic symphysis. The cosmetic results [Figure - 3] and [Figure - 4] of this procedure are excellent. However, the long-term functional results are still awaited because most of the patients have not yet reached full sexual maturity. Randolph et al  reported on a small series of patients who had undergone clitoral recession and indicated that the functional results were quite good.
All said and done, the problem of sex assignment to a child with ambiguous genitalia has its own social tentacles in the Indian perspective. Most of the parents of such children insist on a male sex assignment irrespective of the genotype and the surgical feasibility. This is because of the social stigma attached with the female child in the lower socioeconomic stratum. Another issue that has a decisive role in the sex assignment is the "mental sex" of the child. Historically, it has been assumed that the psychosexual development of infants with an intersex disorder is largely the result of rearing rather than intrinsic. However in the past decade, it has become apparent that testosterone imprinting of the fetal brain may play a role in determining a male sex orientation. Clinical studies in girls with CAH have confirmed the widely held impression that such children engage in more typically male-like behavior patterns than their unaffected peers  and occasionally may have difficulties with adjustment to their assigned gender.  Nonetheless, the majority of such girls do not overtly demonstrate problems with sexual identity, although scientific studies are sparse. Until further data become available, caution should be exercised when a recommendation is made that the sex of rearing should differ from the chromosomal sex. Such cases warrant careful individual consideration. Psychological counseling of affected individuals and their parents may be beneficial. 
| Conclusions|| |
Management of children with ambiguous genitalia continues to be one of the most challenging diagnostic as well as therapeutic problems facing the pediatric urologist. The treatment of these anomalies needs a multidisciplinary approach involving the endocrinologist, neonatologist and pediatric urologist. At the same time, because of the rarity of these abnormalities, a large experience is needed in order to properly manage the large number of variations and complexities seen.
Finally, while assigning sex to a child with ambiguous genitalia, the karyotype, the phenotype, mental sex and the parental wishes should be given due consideration. Decision should be individualized on the basis of these factors.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]