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RESEARCH ARTICLE
Year : 2003  |  Volume : 19  |  Issue : 2  |  Page : 145-151
 

Surgical management of ambiguous genitalia in infants and children: An SGPGI experience


Department of Urology and Renal Transplanation and Department of Medicine Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Correspondence Address:
Anant Kumar
Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014
India
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Source of Support: None, Conflict of Interest: None


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   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 2019 Sep 17];19:145-51. Available from: http://www.indianjurol.com/text.asp?2003/19/2/145/37147



   Introduction Top


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 Top


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].

Male pseudohermaphroditism:

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:

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 Top


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 Top


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. [1] 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. [2] 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. [3] 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. [4] 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. [5] Dono­hoe and Hendren also favor early reconstruction, suggest­ing that 3 to 6 months of age may be the optimal time. [6] 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 [7] and Randolph et al [8] 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 [9] 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 [10] and occa­sionally may have difficulties with adjustment to their as­signed gender. [11] 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. [10]


   Conclusions Top


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.

 
   References Top

1.Donohoe PK. Crawford JD, Hendren WH. Management of neonates and children with male pseudohermaphroditism. J Pediatr Surg 1977: 12: 1045-1057.  Back to cited text no. 1    
2.Donohoe PK. Crawford JD. Ambiguous genitalia in the newborn. In: Welch KJ. Randolph JG. Ravitch MM et al (ed 4). Chicago. IL. Year book. 1986, p. 1374.  Back to cited text no. 2    
3.Nihoul-Fekete C. Lortat-Jacob S. Cachin O. et al. Preservation of gonadal function in true hermaphroditisnm. J Pediatr Surg 1984: 19: 50-55.  Back to cited text no. 3    
4.Canty TG. The child with ambiguous genitalia : A neonatal surgi­cal emergency. Ann Surg 1977: 186: 272-281.  Back to cited text no. 4    
5.Sharp RJ. Holder TM, Campbell PH et al. Neonatal genital recon­struction. J Pediatr Surg 1987; 22: 168-171.  Back to cited text no. 5    
6.Donohoe PK. Hendren WH. Perineal reconstruction in ambiguous genitalia infants raised as females. Ann Surg 1984; 200: 363-371.  Back to cited text no. 6    
7.Nihoul-Fekete C. Feminization genitoplasty in the intersex child. In : Josso N (ed) : The intersex child. Pediatric Adolescent Endocrinology. vol 8. Basel. Switzerland. Karger, 1981 pp 247-­260.  Back to cited text no. 7    
8.Randolph JG, Wellington H. Rathlev MC. Reduction cliteroplasty in females with hypertrophied clitoris. J Pediatr Surg 1970: 5: 224­-231.  Back to cited text no. 8    
9.Randolph JG. Wellington H, Rathlev MC. Cliteroplasty for females born with ambiguous genitalia. J Pediatr Surg 1981: 16: 882-887.  Back to cited text no. 9    
10.Hines M. Kaufman FR. Androgen and the development of human sex - typical behavior : rough and tumble play and sex of preferred playmates in children with congenital adrenal hyperplasia (CAH). Child Dev 1994: 65: 1042-1053.  Back to cited text no. 10    
11.Reiner XG. Sex assignment in the neonate with intersex or inad­equate genitalia. Arch Pediatr Adoles Med 1997; 151: 1044-1045.  Back to cited text no. 11    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]



 

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