Continuing Education Activity

Hypospadias is one of the most common urogenital anomalies in newborn males. It is defined as the combination of the displacement of the urethral opening on the ventral side of the penis, an abnormal ventral curvature of the penis, called “chordee,” and an abnormal distribution of the foreskin with a “hood” present dorsally and deficient foreskin ventrally. Hypospadias can cause problems in voiding, and in adults, it can cause sexual problems and infertility. This activity reviews the evaluation and treatment of hypospadias and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

• Describe the pathophysiology of hypospadias.
• Review the clinical features of hypospadias.
• Outline the management strategies and timing of surgery for hypospadias.
• Summarize the importance of collaboration amongst the interprofessional team to enhance the care of patients with hypospadias.

Introduction

Hypospadias is one of the most common urogenital anomalies in newborn males.[1][2] It is the second most common congenital anomaly in males after undescended testis.[1] It is defined as the combination of the displacement of the urethral opening on the ventral side of the penis, an abnormal ventral curvature of the penis, called “chordee,” and an abnormal distribution of the foreskin with a “hood” present dorsally and deficient foreskin ventrally. Hypospadias can cause problems in voiding, and in adults, it can cause sexual problems and infertility. It is also associated with abnormal body-image perception. The timely diagnosis and early surgical intervention have significantly improved the functional and cosmetic outcomes in recent years.

Etiology

The etiology seems multifactorial, and various theories have been proposed.

• Genetic and familial factors- These factors are more common in the anterior and middle forms of hypospadias.[1] In 7% of cases, close relatives, including father and brother, will have hypospadias.[1] It can be equally transmitted from maternal and paternal sides, but in only 30% of cases, a clear genetic cause is found.[1] A number of genetic syndromes can be associated with hypospadias, but the most common are WAGR (Wilms tumor, aniridia, genitourinary malformation, mental retardation), Denys-Drash syndrome, and Smith-Lemli-Opitz syndrome.[1][3] Boys born as a result of an intracytoplasmic sperm injection (ICSI) procedure done for severe sperm defects of their fathers are at risk of developing hypospadias.[4]
• Hormonal factors- As hypospadias sometimes can be associated with cryptorchidism and micropenis, hormonal factors, particularly the imbalance between androgen and estrogen, are thought to play a major role in abnormal development of the urethra and the foreskin.[1][5] There is evidence that disrupted exposure to the androgen in fetal life can cause reduced anogenital distance, which has been found in boys with hypospadias.[1] Disorders of sexual development (DSD) are more common in infants with posterior hypospadias.[1] Testicular dysgenesis syndrome (TDS) has been postulated as a cause of hypospadias, cryptorchidism, male infertility, and testicular cancer.[1] TDS originates from maldevelopment of the testes and can be an important hormonal factor causing hypospadias.[1]
• Environmental factors- Animal studies identified a few “environmental-endocrine disruptors,” causing hypospadias.[1][5] One recent human study also found the possible contribution of maternal exposure to hormonally active hazardous air pollutants (HAHAP) on hypospadias.[6] 
• Maternal factors- Maternal hypertension, oligohydramnios, preterm delivery, and monochorionic twinning all are associated with severe hypospadias.[1] Therefore, inadequate exposure of fetal testes to human chorionic gonadotrophin (hCG) has been postulated as a cause of hypospadias. However, no cause-effect relationship has yet been postulated.[1]

Epidemiology

The exact incidence of hypospadias at birth is difficult to estimate because of methodological constraints.[1] According to the surveillance systems in the United States, the incidence is around 1 in 200 to 300 male live births.[7] In comparison, an incidence of 18.6 per 10,000 live births has been described in Europe.[1] Although some studies expressed concern about the increased occurrence of hypospadias, other studies could not find it.

Pathophysiology

The male external genital organs develop in two stages. The initial hormone-independent stage develops between 8 and 12 weeks of gestation. In this stage, the external genitalia is bipotential, consisting of a genital tubercle, two genital folds, and two labioscrotal swellings. In the second phase, in the presence of the Y chromosome and the testosterone secreted from the fetal testes (and its conversion to dihydrotestosterone-DHT in local skin), the genital tubercle elongates, and the urethral plate (UP) develops into a groove towards the tip of the genital tubercle. The genital folds fuse to form the penile urethra, and the labioscrotal swellings fuse in the midline to form the scrotum. The genital tubercle enlarges and forms the penis. Finally, the foreskin and the glans fuse in the midline. This stage takes place between 11 and 16 weeks of gestation.[1] Any disruption in this development will cause hypospadias.[3]

History and Physical

The parents may be concerned about the abnormal location of the urethral meatus of male infants. As the meatus is often stenosed, it may cause narrowing and splaying of the urinary stream and wetting of the undergarments during micturition. There may be a difficulty in micturition in the standing position. Posterior hypospadias may be associated with cryptorchidism and bifid scrotum, giving the impression of ambiguous genitalia. The curvature of the penis can be the presenting feature, particularly in adults, and this is more pronounced during erection. This can cause difficulty in sexual intercourse and failure to deposit the semen in the vagina, leading to infertility. Hypospadias is classified according to the position of the urethral meatus into three categories which include anterior hypospadias where the location is glandular (under the surface of the glans penis), coronal (at the corona glandis), or subcoronal (at the junction of the corona and the body of the penis). This is the commonest variety.

In middle hypospadias, the location of the meatus is distal penile, midshaft penile, or proximal penile. In posterior hypospadias, the location is penoscrotal (at the junction of the penis and the scrotum), scrotal (between the two halves of the scrotum), or perineal (at the perineum, associated with bifid scrotum).[1] There are two additional varieties of hypospadias. The first is megameatus intact prepuce (MIP), which is characterized by coronal hypospadias, wide-open navicular fossa, nonfused glans, and normally developed circular foreskin.[1] The second is hypospadias sine hypospadias, which is characterized by the chordee, distorted foreskin, and a normally positioned meatus.[1][2][3]

However, the definite classification is possible only during surgery, taking into account the size of the penis, the glans, and the urethral plate, the degree of penile curvature, the division of the corpus spongiosum, and associated scrotal anomalies.[1]

Evaluation

Endocrine evaluation is particularly important in the presence of posterior hypospadias, ambiguous genitalia, and cryptorchidism.[1] Karyotype and testing for 17-hydroxy-progesterone are recommended.[2] Ultrasound examination of the genitourinary system should be considered in individuals with posterior and complex hypospadias.[1] The Mullerian remnants in the form of a utricular cyst and dilated utriculus can be seen in 50% of perineal hypospadias and can cause urinary obstruction. Endoscopic examination of the urethra can reveal abnormalities not detected by ultrasound.[1]

Treatment / Management

The goal of surgery is to improve the genital appearance, prevent splaying of the urinary flow, and enabling the individual to urinate in the standing position, avoid sexual difficulties associated with curvature, and enable deposition of the semen into the vagina during sexual intercourse. However, isolated glandular hypospadias often does not need surgical correction.[1] 

If presented in the early part of life, commonly hypospadias is surgically corrected by 6 to 18 months of age, depending on the severity.[8] Some surgeons feel that micropenis, defined as the penile length below the third percentile, may cause technical difficulties and advocate testosterone supplement preoperatively. However, only moderate penile growth occurs in the initial years of life, and testosterone supplementation is not supported by high-quality evidence.[1] As a result, delaying surgery is of little benefit. This is important in another aspect as the adolescents who cannot recall the genital surgery were more likely to feel a positive body image than those who can. The “genital awareness” of an individual starts at the age of 18 months, and as a result, surgery in early life can reduce the psychological burdens. Moreover, surgery in the later stage of life is associated with more complications, presumably because of increased urethral secretions and nocturnal erections. However, other studies did not find any association between the age of the repair and the risk of complications. 

Surgical repair:

The basic requirements are the use of magnification, atraumatic tissue handling, using fine instruments and suture materials, and adequate hemostasis.[8] Most of the anterior and middle hypospadias are repaired in a single step.[8] However, in the posterior variety often, a two-step procedure is needed.[2][8] The surgery for hypospadias involves the following steps:

1. Penile degloving: This is essential to assess the degree of chordee. All penoscrotal tethering bands should be released.[2]
2. Orthoplasty: This is done for the correction of the ventral curvature to achieve a straight penis while maintaining penile length and erection.[2] Usually, curvature below 15 degrees does not need any correction, while more than 30 degrees needs an extensive procedure.[2] After degloving, the glans wings are raised, and the corpus spongiosum is released from the corporal bodies. This is followed by dorsal placation, proximal dissection of the spongiosum, and distal division of the urethral plate. Several small cuts are made in the fibrotic spongiosum. Next, corporotomy is done incising the tunica of the corpora cavernosa, and the resulting ellipsoid defect is covered with a graft from the skin, intestinal submucosa, or testicular tunica vaginalis.[2]
3. Urethroplasty: Urethral reconstruction is done in various ways, often guided by the experience and skill of the surgeons. These include urethral plate (UP) tubularization, UP augmentation, and UP replacement. In UP tubularization, the UP distal to the meatus is tubularized in various ways, including the glandular approximation procedure (GAP), tubularized incised plate repair (TIP), and urethral mobilization.[9][10][11] UP augmentation is done with preputial grafts using different techniques.[12][13][14] UP replacement is done in anterior hypospadias with severe chordee and poor UP.[2] In such a case, a two-stage urethroplasty is often done by urethral transaction and preputial graft placement as the initial procedure, followed by a tubularization after six months.[2] Naturally and synthetically derived bioengineered materials have also been used in the reconstruction.[1]
4. Glansplasty: This is the reconstruction of the glans penis, where extensive dissection of the glans is done to create a midline, anterior-based flap. The tubularized urethra is brought out through the incision made on the glans. Finally, cosmetic skin coverage is done to give the appearance of a circumcised penis.[2]

Approved surgical techniques for hypospadias repair might differ based on the meatal location as follows. The meatal advancement and glanuloplasty incorporated (MAGPI) operation for the distal meatus is highly recommended, as it might result in satisfactory outcomes. Moreover, the low complication rate and acceptable aesthetic and cosmetic results are among the advantages. The specific demand for a meticulous technique under the supervision of an expert surgeon to obtain the optimal results is among the limitations. A precise patient selection for this outpatient procedure has a critical role in the optimization of the surgical outcome. The patients not suitable for a MAGPI procedure are those with thin or stiff skin around the meatus and a meatus, which is located excessively proximal or wide.[15] This technique was also utilized for cases with a meatus located 1-2 centimeters proximal to the coronal sulcus. However, later it was decided to perform the procedure selectively on the coronal cases. In order to avoid a retrusive meatus, the precise approximation of granular tissue in a couple of layers is highly recommended. Among the well-known complications of the MAGPI procedure, meatal stenosis must be mentioned, and generously deep Heineke-Mikulicz rearrangement might be preventive. The incision might be started within the meatus and extended in a distal direction. The demand for re-do surgery is extremely limited to approximately 1%.[16] 

Repairing the non-coronal distal hypospadias might be performed via either the Mathieu technique or the tubularized incised plate urethroplasty (TIP). Patient selection for these techniques should also be precise, which means those patients with even distal but thin meatus extending to the penoscrotal junction are not appropriate choices for the technique. Another exclusion criteria for utilizing the TIP or Mathieu technique would be a high grade of ventral curvature of more than 30 degrees, which should be characterized following complete degloving. These patients with excessive chordee should be approached via proximal hypospadias repair techniques. Also, previously considered as a contraindication for TIP repair, the narrow urethral plates equivalent to an average of 6 mm prior to incision are now candidates for distal TIP repair.[17][18][19] A few modifications have been added to the original TIP; for instance, grafting to fill the defect following the incision might result in improved outcomes without a significant increase in specific complications, including meatal stenosis or urethral strictures.[20] Utilizing TIP might not be limited to the distal hypospadias, as it can be used for even more proximal cases of midshaft or proximal hypospadias. The major consideration in those patients would be the final degree of ventral curvature after complete degloving, which should be less than 30 degrees.

Methods to correct persistent chordee after degloving:

Curvatures of less than 30 degrees might be preferably addressed with a dorsal plication procedure only, while children with greater than 30 degrees of chordee usually require ventral corporotomy. A significant increase in the rates of recurrent curvature, recurrent fistula, and dehiscence at the site of urethroplasty was noticed when dorsal plication and not ventral corporotomy is used to address the greater degrees of ventral curvatures. Ventral corporotomy might be optimally undertaken through a single semi-circumferential incision at the maximal point of bending, or three 4 to 8 o'clock incisions at the maximal point of bending and 4 mm distally and proximally. The resultant defect in a single corporotomy, which is more versatile than the multiple ones, might be covered with several options, including the small intestine submucosa, etc. Following ventral corporotomy and grafting, a one or two-stage flap technique might be undertaken for urethroplasty. To avoid recurrent chordee, urethral plate transection is recommended when ventral curvature is persisting after corporotomy. However, a urethroplasty can be performed safely when no curvature is present following ventral corporotomy.[21]

Differential Diagnosis

Management of a patient with hypospadias should start with a comprehensive physical examination and review of organ systems to exclude several possible accompanied clinical syndromes. Several differential diagnoses might be considered while approaching a patient with hypospadias. Enzymatic defects, including dihydrotestosterone (DHT), might result in masculinization defects of varying degrees.

The production of DHT, as a highly potent androgen, is correlated with the function of the SRD5A2 gene. In contrast, the mutations of the mentioned gene might clinically present with perineoscrotal hypospadias and female phenotype. In order to differentiate this pseudovaginal hypospadias from other disorders of sexual differentiation, remarkable virilization, and lack of gynecomastia during puberty should be considered.[22]

Prognosis

Overall, the prognosis is good for both the mild and the proximal varieties of hypospadias, provided the defect is repaired early. Lower urinary tract symptoms, including obstructive urinary flow, hesitancy, etc. are common in men after surgical repair of hypospadias, particularly the posterior type. Meatal stenosis, fistula, and urethral stenosis are common complications of hypospadias surgery. Therefore, long-term follow-up until the attainment of “genital maturity” is needed.[8] After surgical repair, approximately 70% of patients feel satisfied with their genital appearance. Of these, the posterior and the complex hypospadias have less favorable cosmetic outcomes. Some men feel afraid of being judged by others because of the “altered” genital appearance. Sexual function is satisfactory in 80% of the cases.

Complications

Most of the early postoperative complications are due to improper surgical technique and can easily be prevented by proper procedural planning and better tissue handling. These complications include edema, hematoma formation, wound dehiscence, flap necrosis, urethrocutaneous fistula, penile torsion, accidental removal of the ureteral stent, etc.[23] Optimal hemostasis is to be ensured to avoid any hematoma formation. As mentioned, proper tissue handling is needed to avoid postoperative edema. A circumferential compressive dressing can also limit the degree of postoperative edema.

To avoid flap necrosis and dehiscence, adequate flap mobilization and tension-free repair are needed. Fistula formation is a common complication after reconstructive surgery for hypospadias. Factors contributing to the formation of a fistula include poor tissue handling, distal construction, local infection, etc. All factors have to be kept in mind to avoid any fistula formation.

Accidental stent dislodgements can be avoided by adequate anchoring. Late complications include meatal stenosis, fistula formation, diverticulae formation, stricture formation, persistent chordee, torsion, etc. Late complications possibly arise due to unaddressed early complications. Children who develop wound infection, dehiscence, hematoma formation, etc. are at risk for developing further complications later. These complications generally require reoperation for their correction.[24]

Deterrence and Patient Education

Hypospadias is one of the commonest congenital anomalies in children. Various techniques have been described for its surgical repair. Early reconstruction provides the best functional and cosmetic outcomes. It has been highlighted that around 25% of the patients with hypospadias require a reoperation. Of these, less than half will require a second surgery within one year. Thus, patients and parents should be encouraged to consult skilled pediatric surgeons, not only for the reconstructive surgery but also for adequate follow up to ensure favorable long-term outcomes.[25]

Pearls and Other Issues

• Examination of the genitalia is part of routine newborn care
• Hypospadias should be ruled out before the circumcision procedure
• Early surgical intervention improves the cosmetic and functional outcome, reduces psychological morbidities, and the risk of postoperative complications
• In posterior and complex varieties, further endocrine, genetic and urological investigations should be done

Enhancing Healthcare Team Outcomes

Hypospadias is a common genital defect in males. Early diagnosis and single-step surgery can restore the functional capacity and cosmetic appearance in most cases. This condition is best managed by an interprofessional team consisting of the urologist, neonatologist, pediatric surgeon, reconstructive surgeon, endocrinologist, geneticist, nurse, and mental health counselor. Careful examination of the genitalia should be done at birth and, of course, before planning circumcision.