 | AUTHOR INFORMATION
| Section 1 of 10    |
Authored by John M Gatti, MD, Assistant Professor, Department of Pediatric Surgery and Urology, University of Missouri School of Medicine; Assistant Professor, Director, Minimally Invasive Urology, Department of Pediatric Surgery and Urology, Children's Mercy Hospital
Coauthored by Andrew J Kirsch, MD, FAAP, FACS, Professor of Urology, Emory University School of Medicine; Fellowship Director, Department of Urology, Division of Pediatric Urology, Children's Healthcare of Atlanta; Howard M Snyder III, MD, Professor, Department of Surgery, Division of Pediatric Urology, University of Pennsylvania School of Medicine
John M Gatti, MD, is a member of the following medical societies:
American Academy of Pediatrics,
American Urological Association,
Society for Fetal Urology, and
Society for Pediatric Urology
Edited by M David Bomalaski, MD, FAAP, Chief of Medical Staff, 3rd Medical Group, Elmendorf Air Force Base; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc;
Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond;
Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine;
and William J Cromie, MD, MBA, President and Chief Executive Officer, Department of Health Care, Capital District Physicians' Health Plan
eMedicine Journal, May 24 2006, VOLUME 7,
Number 5
| INTRODUCTION
| Section 2 of 10  |
Background: Hypospadias is an abnormality of anterior urethral development in which the urethral opening is ectopically located on the ventrum of the penis proximal to the tip of the glans penis. The opening may be as proximal as the scrotum or perineum. The penis is more likely to have associated ventral shortening and curvature, called chordee, with more proximal urethral defects.
The earliest medical text describing hypospadias dates back to the second century AD and was the work of Galen, the first to use the term. During the first millennium, the primary treatment for hypospadias was amputation of the penis distal to the meatus. Since that time, many have contributed to development of modern hypospadias repair. Over 300 different types of repairs have been described in the medical literature. Although most reports have been in the last 60 years, most basic techniques were founded over a century ago.
Modern anesthetics, instruments, sutures, dressing materials, and antibiotics have improved clinical outcomes and have created a high standard of care. In most cases, this means a single-stage repair within the first year of life on an outpatient basis.
Pathophysiology: Hypospadias is a congenital defect that is thought to occur embryologically during urethral development, from 8-20 weeks’ gestation. The external genital structures are identical in males and females until 8 weeks’ gestation, but the genitals develop a masculine phenotype in males primarily under the influence of testosterone. As the phallus grows, the open urethral groove extends from its base to the level of the corona. The classic theory is that the urethral folds coalesce in the midline from base to tip, forming a tubularized penile urethra and median scrotal raphe. This accounts for the posterior and middle urethra. The anterior or glanular urethra is thought to develop in a proximal direction, with an ectodermal core forming at the tip of the glans penis, which canalizes to join with the more proximal urethra at the level of the corona. The higher incidence of subcoronal hypospadias supports the vulnerable final step in this theory of development.
In 2000, Baskin proposed a modification of this theory in which the urethral folds fuse to form a seam of epithelium, which is then transformed into mesenchyme and subsequently canalizes by apoptosis or programmed cell resorption. Similarly, this seam theoretically also develops at the glanular level, and the endoderm differentiates to ectoderm with subsequent canalization by apoptosis.
The prepuce normally forms as a ridge of skin from the corona that grows circumferentially, fusing with the glans. Failure of fusion of the urethral folds in hypospadias impedes this process, and a dorsal hood of prepuce results. On rare occasions, a glanular cleft with intact prepuce may occur, the megameatus intact prepuce (MIP) variant.
Chordee, or ventral curvature of the penis, is often associated with hypospadias, especially more severe forms. This is thought to develop secondary to a growth disparity between the normal dorsal tissue of the corporal bodies and the attenuated ventral urethra and associated tissues. Rarely, the abortive spongiosal tissue and fascia distal to the urethral meatus forms a tethering fibrous band that contributes to the chordee.
The location of the abnormal urethral meatus classifies the hypospadias. Although several different classifications have been described, most physicians use the classification that was proposed by Barcat and modified by Duckett, which describes the location of the meatus after correction of any associated chordee. Descriptive locations include anterior (glanular and subcoronal), middle (distal penile, midshaft, and proximal penile), and posterior (penoscrotal, scrotal, and perineal). The location is anterior in 50% of cases, middle in 20%, and posterior in 30%, with the subcoronal position being the most common overall.
Frequency:
- In the US: Hypospadias occurs in approximately 1 in every 300 male births in the United States. In several countries, the incidence of hypospadias is rising. In the United States, the rate of hypospadias doubled from 1970-1993. Although some have suggested that the increased incidence is, in reality, an increase in reporting of minor grades of hypospadias, increases in severe hypospadias have been noted as well. Increasing sensitivity of surveillance systems alone cannot explain this 2-fold increase.
- Internationally: In several countries, the incidence of hypospadias is rising.
Mortality/Morbidity: The treatment for hypospadias is surgical repair. Hypospadias is generally repaired for functional and cosmetic reasons. The more proximally ectopic the position of the urethral meatus, the more likely the urinary stream is to be deflected downward, which may require urinating in a sitting position. Any element of chordee can exacerbate this abnormality. Fertility may be affected. The abnormal deflection of ejaculate may preclude effective insemination, and significant chordee can preclude vaginal insertion of the penis or be associated with inherently painful erections. Although the most minor forms of hypospadias are physiologically insignificant, they too may merit repair based on the potential psychological insult of having a genital anomaly.
Race: The incidence of hypospadias is greater in whites than in blacks, and it is more common in those of Jewish and Italian descent.
History: Hypospadias is an abnormality of anterior urethral development in which the urethral opening is ectopically located on the ventrum of the penis proximal to the tip of the glans penis. The opening may be as proximal as the scrotum or perineum. The penis is more likely to have associated ventral shortening and curvature, called chordee, with more proximal urethral defects. This is usually discovered at birth.
Obtain a thorough history and physical examination, including any history of a familial pattern of hypospadias, any past medical history or comorbidity, and a physical assessment focusing on the meatal location, glans configuration, skin availability, and chordee.
Physical: Although the diagnosis of hypospadias has been made on prenatal fetal ultrasonography, the diagnosis is generally made upon examination of the newborn infant.
- A dorsal hood of foreskin and glanular groove are evident, but upon closer inspection, the prepuce is incomplete ventrally and the urethral meatus is noted in a proximally ectopic position. Rarely, the foreskin may be complete, and the hypospadias is revealed at the time of circumcision. If hypospadias is encountered during neonatal circumcision, after the dorsal slit has been performed, the procedure should be halted, and the patient referred for urologic evaluation.
- Chordee may be readily apparent or only discernible during erection. Proximal hypospadias is commonly associated with a bifid scrotum and penoscrotal transposition, in which the rugated scrotal skin begins lateral to the penis, instead of its normal posterior origin.
Causes: Several etiologies for hypospadias have been suggested, including genetic, endocrine, and environmental factors.
- Genetic factors
- A genetic predisposition has been suggested by the 8-fold increase in incidence of hypospadias among monozygotic twins compared to singletons. This finding may relate to the demand of 2 fetuses for human chorionic gonadotropin (HCG) produced by a single placenta, with an inadequate supply during critical periods of urethral development.
- A familial trend has been noted with hypospadias. Fathers of children with hypospadias have been noted to be affected in 8% of patients, and 14% of brothers of children with hypospadias are affected as well. The inheritance likely is polygenic.
- Endocrine factors
- A decrease in available androgen or an inability to use available androgen appropriately may result in hypospadias. In a 1997 report by Aaronson et al, 66% of boys with mild hypospadias and 40% with severe hypospadias were found to have a defect in testicular testosterone biosynthesis. Mutations in the 5-alpha reductase enzyme, which converts testosterone (T) to the more potent dihydrotestosterone (DHT), have been associated with hypospadias. A recent 1999 report by Silver et al found nearly 10% of boys with isolated hypospadias had at least 1 allele affected with a 5-alpha reductase mutation. Although androgen receptor deficits, quantitative or qualitative, have been shown to result in hypospadias, this is thought to be a relatively infrequent occurrence and other factors are more commonly implicated.
- A higher incidence of hypospadias in winter conceptions has also been proposed. Theoretically, this may be related to the effect of daylight on pituitary function, which, in turn, affects the maternal and fetal hormonal milieu; however, other authors have not noticed this association.
- A 5-fold increased risk of hypospadias appears to exist in males born through in vitro fertilization (IVF) when compared to a control group. This may reflect maternal exposure to progesterone, which is commonly administered in IVF protocols. Progesterone is a substrate for 5-alpha reductase and acts as a competitive inhibitor of the T-to-DHT conversion.
- Other factors that contribute to infertility, such as underlying endocrinopathies or fetal endocrine abnormalities, may play a role.
- Environmental factors: The concept of endocrine disruption by environmental agents is gaining popularity as a possible etiology for hypospadias and as an explanation for its increasing incidence.
- Estrogens have been implicated in abnormal penile development in many animal models. Environmental substances with significant estrogenic activity are ubiquitous in industrialized society and are ingested as pesticides on fruits and vegetables, endogenous plant estrogens, in milk from lactating pregnant dairy cows, from plastic linings in metal cans, and in pharmaceuticals.
- A study by Hadziselimovic in 2000 described an increase in estradiol concentration in placental basal syncytiotrophoblasts of boys with undescended testes compared to a control population. Undescended testes and hypospadias have been associated, but increased estradiol concentration has not been implicated in hypospadias per se. This may support the association of hypospadias with increasing parity, increasing maternal age, and low birth weight noted in some studies in relation to lifelong exposure to environmental disruptors and a possible cumulative effect.
| DIFFERENTIALS
| Section 4 of 10 |
Ambiguous Genitalia and Intersexuality
Circumcision
Genital Anomalies
Other Problems to be Considered:
Undescended testes and inguinal hernias are the most common anomalies associated with hypospadias; look for undescended testes and inguinal hernias during the review of symptoms and physical examination. In 1981, a review by Khuri of over 1000 patients with hypospadias found the incidence of undescended testes and inguinal hernias at 9% each. With more severe forms of hypospadias, the incidence of undescended testes exceeded 30% and the incidence of inguinal hernias approached 20%.
The combination of hypospadias and undescended testis can be an indicator of an underlying intersex disorder. In a 1999 study by Kaefer et al, intersex states were identified in approximately 30% of patients with unilateral or bilateral undescended testes and hypospadias, and more proximal meatal location carried a higher association with intersex states than more distal meatal location. If any gonad was nonpalpable, the incidence rose to 50%; however, if both gonads were palpable, the incidence was only 15%.
Imaging Studies:
- Upper urinary tract anomalies are rarely associated with hypospadias but do not justify routine imaging in these patients unless other organ system anomalies are present. Other associated findings occur more commonly (eg, enlarged prostatic utricle, low-grade vesicoureteral reflux) but are of little consequence clinically unless other symptoms merit evaluation.
| TREATMENT
| Section 6 of 10 |
Surgical Care: The goals of treating hypospadias are to create a straight penis by repairing any chordee (orthoplasty), to create a urethra with its meatus at the tip of the penis (urethroplasty), to re-form the glans into a more natural conical configuration (glansplasty), to achieve cosmetically acceptable penile skin coverage, and to create a normal-appearing scrotum. The resulting penis should be suitable for future sexual intercourse, should enable the patient to void while standing, and should present an acceptable cosmetic appearance.
- Timing of surgery
- Before 1980, hypospadias repair was performed in children older than 3 years because of the larger size of the phallus and a technically easier procedure; however, genital surgery at this age (when genital awareness occurs) can be associated with significant psychological morbidity, including aberrant behavior, guilt, and gender identity confusion.
- Currently, most physicians attempt to repair hypospadias when the child is aged 6-18 months, trending toward earlier intervention. This has been associated with an improved emotional and psychologic result.
- Types of repair: The specific techniques for hypospadias repair are beyond the scope of this article; however, the types of repairs can be generically grouped, and the approach to the repair is relatively standard.
- After fully assessing the penile anatomy, the shaft skin of the penis is degloved to eliminate any skin tethering, and an artificial erection is performed to rule out any chordee. Mild-to-moderate chordee may be repaired by excising any ventral fibrous tethering tissue or by plicating the dorsal tunics of the corporal bodies, compensating for any ventral-to-dorsal disproportion. More severe chordee may require grafting of the ventral corporal bodies using synthetic, animal (small intestinal subunit), cadaveric, or autologous tissues (tunica vaginalis or dermal grafts) to avoid excessive shortening of penile length. On rare occasion, the urethral plate may be tethered and may transection of the plate may be required, precluding the use of native urethral tissues for urethroplasty.
- The urethra may be extended using a variety of techniques. These techniques are generally categorized as primary tubularizations, local pedicled skin flaps, tissue grafting techniques, or meatal advancement procedures.
- The tubularized incised plate (TIP) repair has become the most commonly used repair for both distal and midshaft hypospadias. This concept was initially described by Dean in 1989 and popularized by Snodgrass a decade later. This technique is a primary tubularization of the urethral plate, with the adjunct of incising the posterior wall of the plate, which allows it to hinge forward (see Image 7). This creates a greater diameter lumen than would otherwise be possible, obviating the routine use of a flap or graft to bridge a short, narrow segment of urethral plate. The procedure has proved adaptable to a variety of settings, and current surveys indicate that this is the procedure of choice for the majority of repairs by most urologists.
- For repeat repairs after unsuccessful surgery for hypospadias when local tissues are unavailable, buccal mucosa has been used for urethral grafting. This tissue is well suited for this purpose because of its availability, characteristics that favor graft success, and its resilience to a moist environment. Urethral stents are generally used for bladder drainage, while healing occurs in all but the most distal hypospadias repairs.
- Steps of repair: Glans flaps are generally mobilized to cover the distal urethral repair, bringing the divergent ventral components to the midline and creating a more conical configuration. The excess dorsal skin is mobilized to the deficient ventral aspect of the penis for final skin coverage.
- The repair of penoscrotal transposition is often performed as a staged procedure because the necessary incisions may compromise the vascular pedicle to skin flaps used in the primary urethroplasty. The repair of penoscrotal transposition is usually deferred at least 6 months to allow for adequate formation of collateral blood supply.
- The repair of hypospadias is generally planned as a single-stage procedure, but excessive chordee (especially if transection of the urethral plate is required), poor skin availability, and small phallic size may be better approached in a staged manner. The chordee is repaired and the skin is mobilized to the ventral penile shaft during the first stage, and the urethroplasty and glansplasty are repaired after the first stage has healed completely.
- Adjuvant hormonal therapy: Although no medical therapy for the correction of hypospadias exists, hormonal therapy has been used as an adjuvant treatment for infants with exceptionally small phallic size. Presurgical treatment with testosterone injections or creams, as well as human chorionic gonadotropin (HCG) injections, has been used to promote penile growth, and some have reported improvement in chordee with lessening in the severity of the hypospadias. Some concern exists that prepubertal androgen therapy may limit normal genital growth at puberty.
| FOLLOW-UP
| Section 7 of 10 |
Complications:
- Immediate postoperative concerns
- Local edema and blood spotting can be expected early after repair and generally do not cause a significant problem.
- Postoperative bleeding rarely occurs and is usually controlled with a compressive dressing. Infrequently, this may require reexploration to evacuate a hematoma and identify and treat the source of bleeding.
- Infection is a rare complication of hypospadias repair in the modern era. Skin preparation and perioperative antibiotics are generally used, and patients are often maintained on an antibiotic course until any stents are removed.
- Long-term issues
- Fistula: Urethrocutaneous fistulization is a major concern in hypospadias repair. The rate of fistula formation generally is less than 10% for most one-stage repairs but rises with the severity of hypospadias, approaching 40% with complex reoperative efforts. Fistulas rarely close spontaneously and are repaired using a multilayered closure with local skin flaps. Still, fistulas may recur in approximately 10% of patients.
- Meatal stenosis: Meatal stenosis, or narrowing of the urethral meatus, can occur. A urethral stent prevents any problems initially, but a fine-spraying urinary stream that is associated with straining to void likely requires operative meatal revision.
- Stricture: Urethral strictures may develop as a long-term complication of hypospadias repair. These are generally repaired operatively and may require incision, excision with reanastomosis, or patching with a graft or pedicled skin flap.
- Diverticula: Urethral diverticula may also form and are evidenced by ballooning of the urethra while voiding. A distal stricture may cause outflow obstruction and result in a urethral diverticulum. Diverticula can form in the absence of distal obstruction and are generally associated with graft- or flap-type hypospadias repairs, which lack the subcutaneous and muscular support of native urethral tissue. The redundant urethral tissue is generally excised, and the urethra is tapered to an appropriate caliber.
- Hair in the urethra: Hair-bearing skin is avoided in hypospadias reconstruction. When incorporated into the urethra, it may be problematic and can result in urinary tract infection or stone formation at the time of puberty. This generally requires cystoscopic depilation using a laser or cautery device or, if severe, excision of hair-bearing skin and repeat hypospadias repair.
Prognosis:
- Present prognosis: With modern anesthetics, instruments, sutures, dressing materials, and antibiotics, hypospadias repair has become quite successful. Long-term studies on the outcomes of hypospadias using current practices are limited. Although some earlier studies have been discouraging, these reflect an era with poorer technical outcomes, increased number of operations, and a lack of appreciation for the psychological morbidity associated with intervention at an older age.
- Future prognosis: Although the nuances of hypospadias repair continue to evolve, the broader future of hypospadias is truly promising. Nontraditional tissue adherence techniques are being developed, including tissue glues and laser-activated soldering techniques that have been shown to improve wound healing and reduce fistula formation. Urethral substitutes are currently under investigation, which may obviate the difficulties associated with severe hypospadias and poor tissue availability. These substitutes are generally acellular synthetic or natural matrices, which can incorporate the patient's normal urethral cellular components. The embryology of hypospadias is being elucidated, and the understanding of its causes is improving; with new information, an exciting new paradigm shift to hypospadias prevention or antenatal intervention may occur.
| TEST QUESTIONS
| Section 8 of 10 |
CME Question 1: Which of the following factors are thought to play a role in the etiology of hypospadias?
A: Enzyme abnormalities such as 5-alpha reductase
B:
Inadequate supply of placental human chorionic gonadotropin
C: Environmental disruptors such as phytoestrogens produced by plants
D: Winter conceptions
E: All of the above
The correct answer is E: All of the factors mentioned have been implicated as causes of hypospadias.
CME Question 2: Which of the following is not accurate regarding the repair of hypospadias?
A: Adjunctive hormonal therapy is sometimes used preoperatively.
B: Urethral stents are commonly used during healing.
C: Surgery is usually delayed until the patient is older than 3 years.
D: Penoscrotal transposition is usually repaired as a staged procedure.
E: Postoperative complications include bleeding, fistula formation, and meatal stenosis.
The correct answer is C: The repair of hypospadias is ideally performed in children younger than 3 years to avoid the potential psychologic morbidity of genital surgery noted in some older children. All other answers are accurate statements.
Pearl Question 1 (T/F): Hypospadias has a familial predilection.
The correct answer is True: An increased incidence of hypospadias has been shown in children and siblings of those with hypospadias.
Pearl Question 2 (T/F): Hypospadias generally requires several surgical procedures for repair.
The correct answer is False: Hypospadias can generally be repaired in a single outpatient operation.
Pearl Question 3 (T/F): Severe hypospadias can be associated with intersex disorders.
The correct answer is True: Severe hypospadias, especially those associated with undescended testes, can be associated with intersex disorders.
Pearl Question 4 (T/F): Isolated hypospadias requires routine upper urinary tract imaging.
The correct answer is False: Hypospadias, without other organ system abnormalities, does not generally require upper urinary tract imaging.
| BIBLIOGRAPHY
| Section 10 of 10 |
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| NOTE: |
| Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER |
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