Steve J. Hodges, MD
Anthony Atala, MD
BASICS
DESCRIPTION
• Common congenital disorder of male external genitalia characterized by a ventrally displaced urethral meatus
– Associated conditions may include:
Ventral chordee
Incomplete foreskin with dorsal hood and ventral deficiency
– May be an isolated defect or may be associated with a significant underlying abnormality
– Classification:
Anterior (distal) 50%: Glandular, coronal, subcoronal, megameatus intact prepuce
Middle (midshaft) 30%
Posterior (proximal) 20%: Penoscrotal, scrotal, perineal
EPIDEMIOLOGY
Incidence
• 1 in 250–300 live male births
• 1 in 80–100 in family history of hypospadias
Prevalence
Prevalence in US for hypospadias ranges between 2.01 and 56.17 per 10,000
RISK FACTORS
• 5× incidence in IVF births compared to controls
• Environmental:
– Because of increases in rates in certain areas an association with chemicals with estrogenic or antiandrogenic effects has been suggested
– Examples include environmental chemicals such as bisphenol A (BPA) and hormones used during pregnancy such as progesterone.
– Genetics (see below)
Genetics
• <5% of cases have genetic cause (2)
• Can be seen in isolated and syndromic genetic abnormalities
• Caused by mutations of genes controlling development of male gonads or penis (eg, homeobox, FGF, and Sonic hedgehog genes)
• 5α-reductase mutations
• Familial propensity
– 10% have affected 1st–3rd degree relative
– 14% of male siblings affected
– 27% concordance in monozygotic twins
PATHOPHYSIOLOGY
• Normal penile development:
– Urogenital folds form on either side of the cloacal membrane, and fuse anteriorly at the genital tubercle
– Lateral labioscrotal folds fuse posteriorly and separate the urogenital and anal membranes
– Under influence of testosterone and DHT, phallus elongates and the genital folds fuse in the midline to enclose urethral proximally to distally
– Canalization of the glans occurs distally, fusing with urethra
– Process complete by 20th wk of gestation
• Glandular hypospadias likely represents failure of distal canalization
• Proximal hypospadias due to failure of fusion of genital folds
• Scrotal or perineal variants result in cleft scrotum
ASSOCIATED CONDITIONS
• Growth restriction (low birth weight and length, small head circumference) has been associated with hypospadias
• Associated anomalies are more common in cases of severe hypospadias
– Cryptorchidism (7–9%)
– Inguinal hernia/hydrocele (9–16%)
– Syndromes:
49 described in which hypospadias is frequent or occasional (Aniridia-Wilms tumor association, Beckwith–Wiedemann, Smith–Lemli–Opitz, Trisomy syndromes [4p, 9p, 13, 18], VACTERL association, XXY, Zellweger, and many others)
78% of these have associated micropenis, cryptorchidism, and/or scrotal anomaly
In presence of hypospadias and cryptorchidism must rule out intersex condition (15% with palpable undescended testicle, 50% with nonpalpable)
• 2–12% have upper tract anomalies (horseshoe kidney, renal ectopia, duplicated ureters, others)
• Enlarged prostatic utricle can be associated with severe cases and may increase risk of UTI or prostatic utricle stone formation
GENERAL PREVENTION
Not possible except by avoidance of environmental agents or medications with estrogenic effects by pregnant women (see “Risk Factors”)
DIAGNOSIS
HISTORY
• Family history of hypospadias
– Any associated congenital anomalies
Exposure of mother to hormonally active agents during pregnancy
• IVF may increase risk of hypospadias
PHYSICAL EXAM
• Determine location of urethral opening
• Evaluate for chordee
• Evaluate foreskin
• Evaluate presence of inguinal hernia, hydrocele, or cryptorchidism
• Severely proximal hypospadias may be associated with bifid scrotum and/or penoscrotal transposition
– Look for other congenital anomalies
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Karyotype and hormonal evaluation to rule out intersex is needed in cases of severe hypospadias and cryptorchidism
Imaging
• No routine imaging necessary for routine hypospadias evaluation
– In setting of intersex evaluation, genitogram or pelvic US may be performed
– VCUG in proximal hypospadias may demonstrate prominent prostatic utricle
Diagnostic Procedures/Surgery
N/A
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
• In cases of proximal hypospadias associated with an undescended testicle differential should include:
• Congenital adrenal hyperplasia
• Mixed gonadal dysgenesis
• Partial androgen insensitivity
• True hermaphroditism
ALERT
Do not perform circumcision in the setting of hypospadias. Hypospadias in the presence of cryptorchidism may signal an intersex disorder.
TREATMENT
GENERAL MEASURES (3)
The general tenets of repair are to move the urethral meatus to an orthotopic location, straighten the penis (repair chordee), and either remove or modify the foreskin to give the appearance or a normal circumcised or uncircumcised penis
MEDICATION
First Line
• There is no specific medical therapy for hypospadias
– Preoperative hormonal therapy (testosterone injections or creams, or HCG injections) may be used to enlarge penile size to aid in repair in cases of small phallus (4)
– However, although a preference for the use of preoperative hormonal therapy is observed in the literature, the exact protocol and benefit is not conclusively determined
– 25–50 mg of testosterone propionate given IM weekly for 3 wk preoperatively is one such approach
SURGERY/OTHER PROCEDURES
• Indications of repair (1):
– Goals are to create a cosmetically normal appearing penis with orthotopic meatus, and straight phallus so the child can in the future void while standing, have sexual intercourse, and effectively inseminate.
– Timing of repair is ideal at 4–6 mo of age, surgeries should be complete by 2 yr (the age of genital awareness)
– Techniques dictated by meatal location, degree of chordee, and skin availability
– Chordee should be repaired 1st (orthoplasty)
– Distal hypospadias: MAGPI, Thiersch–Duplay, tubularized incised plate urethroplasty, Mathieu (perimeatal-based flap)
– Midshaft hypospadias: Tubularized incised plate urethroplasty, Mathieu, onlay island flap
– Proximal hypospadias: 1 stage—Thiersch–Duplay, incised plate urethroplasty, onlay island flap; 2 stage—1st stage repair chordee, second stage 6 mo after 1st (Thiersch–Duplay, incised plate urethroplasty)
In cases of lack of skin may use buccal mucosal graft
Hypospadias revision: Meatoplasty, fistula repair
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
Patient may need revisions for chordee, meatal issues, or recurrent chordee at later dates
Complementary & Alternative Therapies
Psychosocial support for patient and family if needed long term
ONGOING CARE
PROGNOSIS
Most patients have normal penile function for voiding, sexual performance, and insemination
COMPLICATIONS
• Early:
– Bleeding/hematoma—treated with compression or surgical exploration; infection—treated with antibiotics or incision and drainage;
– UTI—treated with appropriate antibiotics;
– Wound dehiscence—requires reoperation 6 mo later
• Late:
– Residual/recurrent chordee—treated with reoperation,
– Meatal stenosis—treated with meatal dilation or meatoplasty
– Urethral stricture—treated with dilation or urethroplasty;
– Urethrocutaneous fistula or urethral diverticulum—treated with excision and repair;
– Hair in urethral repair—treated with endoscopic laser or cauter or excision and repair;
– Lichen sclerosis or balanitis xerotica obliterans—treated with complete excision and buccal graft
FOLLOW-UP
Patient Monitoring
• Follow-up for observation of penile development and complications noted above
– Children may present after toilet training or even as late as adolescence with newly diagnosed complications from repair as an infant
Patient Resources
Urology Care Foundation http://www.urologyhealth.org/urology/index.cfm?article=130
REFERENCES
1. Subramaniam R, Spinoit AF, Hoebeke P. Hypospadias repair: An overview of the actual techniques. Semin Plast Surg. 2011;25(3):206–212.
2. Akre O, Boyd HA, Ahlgren M, et al. Maternal and gestational risk factors for hypospadias. Environ Health Perspect. 2008;116(8):1071–1076.
3. Bhat A. General considerations in hypospadias surgery. Indian J Urol. 2008;24(2):188–194.
4. Netto JM, Ferrarez CE, Schindler Leal AA, et al. Hormone therapy in hypospadias surgery: A systematic review. J Pediatr Urol. 2013;9(6 Pt B):971–979.
ADDITIONAL READING
Macedo A Jr, Rondon A, Ortiz V. Hypospadias. Curr Opin Urol. 2012;22(6):447–452.
See Also (Topic, Algorithm, Media)
• Bifid Scrotum
• Disorder of Sexual Development (DSD)
• Hypospadias Image 
• Penoscrotal Transposition
CODES
ICD9
• 752.61 Hypospadias
• 752.63 Congenital chordee
• 752.69 Other penile anomalies
ICD10
• Q54.0 Hypospadias, balanic
• Q54.1 Hypospadias, penile
• Q54.9 Hypospadias, unspecified
CLINICAL/SURGICAL PEARLS
• More severe cases (proximal) more likely to be associated with an intersex disorder.
• All members of the health care team must clearly understand that circumcision should not be performed if hypospadias is present.