Surgical management of 46,XY differences in sex development

Gonadal interventions

Orchidopexy. Most patients of 46,XY DSD undergoing masculinizing genitoplasty are likely to have testes, many of which are cryptorchid. These testes require early orchidopexy to best preserve potential for fertility. Inguinal testes may be brought down in a single stage into the labioscrotal folds with high success rates. Intra-abdominal testes are best managed laparoscopically; the low ones can be brought down into the scrotum in a single-stage operation. The high intrabdominal testis may be managed in a single-stage or two-stage procedure by the Fowler– Stephen (FS) procedure. This procedure involves division of the testicular vessels and dependence on collateral blood supply from two other sources – artery to the vas and cremasteric artery; hence, a single-staged procedure has a higher testicular atrophy rate compared to two-staged procedure where a gap of a few months is allowed for the collaterals to develop. The Shehata technique is a two-stage procedure which employs traction lengthening of the testicular pedicle without vascular transection. The testicular atrophy rates of this procedure are comparable to those of the staged FS procedure.^[8]

Orchidectomy. It is rare that malignant change occurs in a cryptorchid testis before the third decade of life; hence, orchidectomy is singularly uncommon in childhood. Dysgenetic gonads in 46,XY DSD are beyond the scope of this discussion. However, partial androgen insensitivity syndrome (PAIS) carries a 15–25% lifetime risk of malignant change and surveillance is easier in a scrotal testis.^[9]

Testicular prosthesis, commonly made of silicone, may be chosen by an adolescent with unilateral scrotal testis in select cases—testicular regression, testicular atrophy after orchidopexy, or other surgery. This is ideally undertaken only after completion of pubertal scrotal growth to minimize prosthesis replacements.

Penile reconstruction

The primary concerns in penile reconstruction are correction of ventral curvature/chordee (orthoplasty) and creation of a neourethral tube from the hypospadiac meatus to as close to the glans tip (urethroplasty).

Orthoplasty involves a stepwise surgical progression depending on the severity. Complete degloving of the penile skin may suffice in mild or skin-level tethering. Minor residual chordee thereafter is corrected with dorsal tunical plication, the obvious disadvantage being foreshortening of the already short phallus. More severe chordee requires further techniques such as urethral plate mobilization with the underlying corpora spongiosal delta, urethral plate division, and corporal lengthening procedures (ventral superficial or deep corporotomy incisions) to achieve a complete straightening.^[7,10]

Urethroplasty in proximal and severe hypospadias that are common in DSD are conventionally staged but can be done in a single stage along with orthoplasty. The choice between the two depends on the surgical anatomy, tissue adequacy, vascularity, androgen responsiveness, and surgical expertise. Cases with mild chordee where the urethral plate can be preserved are suitable for single-stage urethroplasty using a variety of techniques dictated by the surgeon’s preference. Commonly employed options are the tubularized incised urethral plate urethroplasty (Snodgrass) or a preputial flap onlay repair (Duckett, Asopa). The Koyanagi technique can also be used to achieve chordee correction and urethroplasty in a single sitting if the preputial anatomy is favorable.

Composite repairs using a combination of urethral plate tubularization (Duplay) along with tubularized preputial flaps (Duckett) have been used. In proximal hypospadias with severe chordee, orthoplasty is achieved with tissue cover for the ventral raw area using hairless skin, inner preputial tissue (vascularized or free graft), or free labial/buccal mucosa graft (Bracka) in the first stage and a delayed urethroplasty as a second stage. The two-stage procedure is the favored approach in most patients and is associated with fewer complications and better outcomes.^[7,10,11]

Phalloplasty, or reconstruction of a penis, is a rare surgical undertaking and indicated in select cases of 46,XY DSD— aphallia (congenital absence of the penis), micropenis (isolated - gonadotropin failure, associated with hypospadias or gonadal abnormalities in primary testicular failure), severe undervirilization syndrome (e.g., PAIS), and some children with bladder or cloacal exstrophy. It is a multistage operation using various free/pedicled flaps to reconstruct the penis and the urethra; neurotization allows for sensation in the neophallus.^[12]

3. UGS remnant or vaginal pouch and Müllerian remnant/ prostatic utricle

Some children with 46,XY DSD and proximal hypospadias, especially due to 5-alpha reductase type 2 (5ARD2) deficiency, have UGS remnants/pseudovaginal pouches distal to the verumontanum with varying length and caliber. They are largely asymptomatic;^[13] small ones are left alone while larger accessible ones are excised or incorporated into the proximal repair during urethroplasty.^[14]

Müllerian remnants and prostatic utricles open at the verumontanum in the rare persistent Müllerian duct syndrome (PMDS). The prostatic utricle is usually asymptomatic. Most symptomatic ones are managed by cystoscopic widening of the mouth to facilitate drainage. A large remnant is excised to eliminate recurrent urinary tract infections (UTIs) and epididymo-orchitis and reduce the risk of endometrial malignancy. The anomalous vas deferens may be entirely or partly embedded in the wall, particularly at its caudal end, and is prone to injury or devascularization during excision. Where complete excision is not safely feasible, it is longitudinally divided with cautious removal of mucosa; this division also facilitates bilateral orchidopexy with ease. An objective, practical guide to the approach, longitudinal splitting or division, or near-total excision has been proposed based on three anatomical parameters: gonadal status, relation to the vas, and degree of Müllerian development.^[15] Excision can be achieved by laparoscopy aided by cystoscopic guidance or other open routes (perineal, transperitoneal, and transvesical anterior sagittal with/without splitting the anterior rectal wall) with risk of seminal vesicle injury.^[16,17] Except for the large ones, these are addressed after the urethroplasty is complete. A low resistance, good caliber neourethra minimizes complications arising from these remnants and many remain asymptomatic. Symptoms are due to retention of urine, UTIs, or mechanical obstructions to the flow of urine and rarely due to mucosal secretions.

A recent debatable approach proposes leaving a male vagina or perineal utricle in situ in boys with perineal hypospadias to minimize genital tissue removal in children without a definite gender identity to facilitate future gender reassignment surgery.^[18]

Management of breast

Gynecomastia is a prominent clinical feature in nearly 80% of adolescent boys and men with PAIS with AR gene variant. This is a cause of psychological distress and hence requires treatment. Medical management includes administration of selective estrogen receptor modulators (tamoxifen, raloxifene, and clomiphene citrate), aromatase inhibitors (testolactone, anastrozole, and letrozole), and androgens. However, their efficacy in PAIS is comparatively modest than in other types of pathological gynecomastia and many require surgical intervention eventually. Bilateral mastectomy by circumareolar or sub-mammary approach yields good results.^[19]

Clitorophallic reduction

Clitorophallic reduction with dorsal neurovascular bundle preservation has replaced complete removal. The reduced phallic structure is anchored at the pubis; its investment retains erotic sensitivity and improves sexual function. In addition, the redundant phallic skin after reduction is used to reconstruct the labia minora that may be missing. Careful vascular preservation prevents necrosis or atrophy of the clitoris. Likewise, large labioscrotal folds may be reduced by a Y-V technique.^[22]

A more conservative surgical approach of corporeal sparing dismembered clitoroplasty (Pippi Salle) preserves the enlarged corpora. The hemi-corpora after separation from one another are rotated laterally and inferiorly and buried in the subdartos plane within the labia majora. The retained corpora in the labia majora have a certain mobility, permitting painless erections and scope for reversibility using the retained erectile tissue for phallic reconstruction in case of gender dysphoria in the future. Apparently, psychologically, it eludes the feeling of castration sensed by some with the excision of the erectile tissue. Anecdotal unpleasant labial engorgement during clitoral erection may be addressed by removing the hemi-corpora through labial incision.^[23]

Surgery for UGS and vaginoplasty

A common urethra and vaginal channel (UGS) in some forms can be associated with post-void dribbling (vaginal voiding), recurrent UTI, and difficulty with coitus. Its length at cystogenitoscopy dictates the choice and complexity of the surgical procedure. These include minor procedures such as cut-back incision (for two separate urethral and vaginal introital orifices, but covered by skin due to mild posterior labial fusion or cranially extended fourchette) and Y-V perineal flap (for vaginal introital stenosis) and partial urogenital mobilization (urethra and vagina mobilized as one vascular unit distal to the pubo-urethral ligaments to preserve urinary continence). More extensive procedures that are used to exteriorize both orifices in a high confluence in congenital adrenal hyperplasia, like Passerini–Glazel procedure and partial or total urogenital mobilization, are rarely employed here.

Most patients with CAIS have an adequate vaginal length that is amenable to dilatation and does not need augmentation. In PAIS, an adequate vagina for satisfactory coitus may be created by dilatation of an existing vaginal pouch by the patient (vaginal dilators or molds) or surgically (Vecchietti procedure with acrylic olive) or by creating a neovagina with variety of material (McIndoe–Reed vaginoplasty [split skin], Davydov procedure [peritoneal flap], or intestinal [ileum or sigmoid vaginoplasty]), each with its outcomes and specific complications.

Gonadectomy

At present, gonadal tumor risk prediction and timing of gonadectomy are based on the molecular diagnosis. In CAIS, both testes are retained to achieve spontaneous puberty, optimal breast and bone development due to high levels of androgens being converted to estrogen by aromatase. The risk of testicular malignancy in CAIS is low before adulthood. In PAIS, the risk of early malignant transformation is higher, warranting gonadal placement in an accessible location for careful surveillance till puberty and early gonadectomy thereafter. In PAIS and some CAIS, gonads are inguinal; the intrabdominal gonads in CAIS are managed with a laparoscopic approach.^[24,25]

Management of breast

Children with 17β-hydroxysteroid dehydrogenase (17βHSD) deficiency and occasionally in PAIS may require breast augmentation either by medical (hormonal supplementation) or surgical (insertion of silicon prosthesis) means.

The management is individualized according to the diagnosis and sex of rearing. Figure 1 illustrates the summary of surgical treatment for specific categories of 46,XY DSD— testosterone biosynthesis or conversion defects and androgen insensitivity syndromes. Illustrative cases are depicted and detailed in Figures 2-4.

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Figure 1:

Summary of surgical management for specific categories of 46,XY DSD. 17βHSD :17-beta-hydroxysteroid dehydrogenase, 5ARD2: 5-alpha-reductase type 2, PST: penoscrotal transposition, UGS: Urogenital sinus.

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Figure 2:

5-alpha reductase (5ARD2) deficiency: The severe chordee (A and B) is corrected and the vaginal pouch (B) excised in the first stage of the repair (A-C), while urethroplasty and correction of penoscrotal transposition are tackled in the second stage (D and E) to achieve a near normal circumcised phallic appearance (F).

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Figure 3:

Partial androgen insensitivity syndrome (PAIS): A 13-year-old child, reared as female and presented at puberty with atypical genitalia and recent change in voice. Note the feminine habitus A and B), poor breast development (B), and sparse axillopubic hair (B and C). Both gonads were palpable in labioscrotal folds (C) beside a short phallic structure (thin arrow, D). There were two orifices: the external meatus (short arrow, D) and vaginal introitus (long arrow, D). The management included bilateral orchidectomy (E), vaginal dilatation, and hormonal supplementation.

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Figure 4:

Persistent Müllerian duct syndrome (PMDS): A 6-year-old child, reared as male, presented with bilateral impalpable undescended testis, symmetrical hypoplastic rugose scrotum and a normal penis (A). Laparoscopy (B,C and D) revealed bilateral low intraabdominal testis with a symmetrical Müllerian remnant. Note the slender uterus (arrow, B), left round ligament (curved arrow) and fallopian tube (straight arrow, C) and right fimbriae (curved arrow, D). A midline division of the uterus with endometrial denudation, fallopian tube excision and bilateral orchidopexy was done.

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