DIAGNOSIS

HYPOSPADIAS

MODULE

REPRODUCTIVE SYSTEM I

CASE

History of Present Illness

Baby Herman is a newborn boy who was born at 39-2/7 weeks’ gestational age. On routine
newborn exam, he is found to have a small defect on the ventral surface of the distal penis.
His prenatal and labor histories are both unremarkable. The patient’s parents are quite
disturbed by the penile defect and are concerned about his ability to have sex and conceive
when he grows up.

Physical Examination

On physical exam, he is a 3725-g male infant. On inspection of his genitalia there is a small
opening on the ventral surface of the penile shaft in the midline from which urine is
expelled. He has a normal scrotum and both testes are descended and appear normal on
palpation.

SALIENT FEATURES

 A newborn male infant.

 Baby Herman was born at 39-2/7 weeks' gestational age, indicating that he was
delivered close to full term.
 On routine newborn examination, a small defect is identified on the ventral
surface of the distal penis. The defect is described as a small opening in the
midline from which urine is expelled.
 Baby Herman's scrotum appears normal on inspection.
 Both of Baby Herman's testes are descended and appear normal on palpation.
 There are no significant abnormalities or complications reported in the patient's
prenatal and labor histories.
 Baby Herman's parents are concerned about his ability to have sex and conceive
when he grows up due to the penile defect.

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 CHIEF COMPLAINT

Penile Defect

DIFFERENTIAL DIAGNOSIS

Hypospadias
 Hypospadias is the most likely diagnosis based on the description provided. It is
characterized by a ventral opening of the urethra on the penis, resulting in an
abnormal urinary meatus.
 The small opening on the ventral surface of the penile shaft observed in Baby Herman
is consistent with hypospadias.

Symptoms:
 Ventral opening of the urethra on the penis
 Abnormal urinary meatus located anywhere along the underside of the penile
shaft
 The severity can vary, with mild cases having the opening closer to the tip of the
penis and more severe cases having the opening closer to the scrotum

Diagnostic Tests:
Physical Examination
 A detailed assessment of the penile anatomy, location of the urinary opening,
and the severity of the defect.
 The physical examination will reveal a ventral opening of the urethra on the
penile shaft in a location other than the tip. This finding confirms the
presence of hypospadias.
Voiding Cystourethrogram (VCUG)
 This imaging test helps visualize the urinary tract and assess any
abnormalities in the urethra and bladder.
 The VCUG may show the abnormal position of the urinary opening and
provide information about the severity and location of the defect.
 The contrast agent will be observed exiting the urethra from a ventral
position instead of the typical meatal position.
Ultrasound
 Used to evaluate the urinary system, including the kidneys, bladder, and
urethra, and to identify any associated anomalies.

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  An ultrasound examination may identify the abnormal position of the urinary
opening and visualize the anatomy of the urethra, bladder, and other
associated structures.
 It can help determine the extent and severity of the hypospadias.

Epispadias
 A rare congenital abnormality in which the urethral opening is located on the dorsal
(upper) surface of the penis.
 It is the opposite of hypospadias.
 However, the description provided does not match the typical features of epispadias,
making it less likely in this case.

Symptoms:
 Dorsal (upper) opening of the urethra on the penis
 Abnormal urinary meatus located on the top surface of the penis
 In severe cases, the bladder may be exposed or the urethra may be split along the
length of the penis

Diagnostic Tests:
Physical Examination
 A thorough examination of the penile anatomy, particularly noting the
presence of a dorsal (upper) opening of the urethra.
Voiding Cystourethrogram (VCUG)
 This test can help determine the extent of the abnormality and any associated
urinary tract abnormalities.
Ultrasound
 Useful for evaluating the urinary system and identifying any associated
structural anomalies.

Urethral Fistula
 An abnormal connection or passageway between the urethra and the skin. It can occur
as a complication of hypospadias repair surgery or as a separate congenital anomaly.
 However, since the opening on the ventral surface of the penis is the only abnormality
described and there is no history of prior surgery, a urethral fistula is less likely.

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 Symptoms:
 Abnormal connection or passageway between the urethra and the skin
 May present as an additional opening near the normal urinary meatus or in a
different location on the penis
 Can lead to urinary leakage from the abnormal opening or difficulty with
urination

Diagnostic Tests:
Physical Examination
 Detailed examination of the penile anatomy to identify additional openings or
abnormal connections between the urethra and the skin.
Imaging Studies
 Depending on the specific location and size of the fistula, imaging tests such as
VCUG, ultrasound, or magnetic resonance imaging (MRI) may be used to visualize
the fistula and surrounding structures.

Meatal Stenosis
 A narrowing of the urethral opening, typically occurring at the meatus (the external
opening of the urethra).
 It can lead to a small or pinhole-like opening.
 However, the description provided does not mention a narrow opening, making meatal
stenosis less likely.

Symptoms:
 Narrowing of the urethral opening, usually at the meatus (external opening of the
urethra)
 Symptoms may include a small or pinhole-like urethral opening
 Urinary flow may be weak or appear as a spray

Diagnostic Tests:
Physical Examination
 Assessment of the urethral opening, looking for signs of narrowing or a
pinhole-like appearance.
Uroflowmetry
 A test that measures the rate and volume of urine flow to assess any obstruction
or narrowing at the meatus.
Urethroscopy
 Direct visualization of the urethra using a flexible or rigid urethroscope to
determine the presence and severity of meatal stenosis.

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 CLINICAL CORRELATION

Baby Herman was born at 39-2/7 weeks' gestational age, indicating that he was
delivered close to full term.
 Baby Herman's penile defect was identified during routine newborn examination.
Being born close to full term suggests that the assessment was performed at an
appropriate time after birth when routine examinations are typically conducted.
 This ensures timely detection and evaluation of any congenital abnormalities,
including hypospadias.
 Baby Herman's gestational age indicates that he had undergone a significant portion of
the normal fetal development.
 It helps establish a baseline for expected anatomy and maturation of the urinary
system, including the genitalia.
 Comparing the observed penile defect to the expected developmental milestones aids
in understanding the nature and severity of the anomaly.
 Babies born prematurely (before 37 weeks of gestation) may have a higher likelihood
of certain congenital abnormalities or conditions.
 However, since Baby Herman was born close to full term, any potential association
between prematurity and the penile defect is less likely.
 It suggests that the defect is primarily related to factors other than prematurity.

On routine newborn examination, a small defect is identified on the ventral surface of

the distal penis. The defect is described as a small opening in the midline from which
urine is expelled.
 The clinical correlation regarding the identification of a small defect on the ventral
surface of the distal penis during routine newborn examination, which is described as
a small opening in the midline from which urine is expelled, suggests the possibility of
hypospadias.
 Hypospadias is a congenital condition where the urethral opening is abnormally
located on the ventral side of the penis instead of the typical meatal position at the tip.
 The characteristic finding of a small opening on the ventral surface of the distal penis
aligns with the typical presentation of hypospadias.
 The identification of the defect during routine newborn examination underscores the
importance of thorough physical assessments in detecting congenital abnormalities
early on.
 Routine examinations allow healthcare providers to promptly recognize and evaluate
conditions like hypospadias, ensuring appropriate management and intervention if
necessary.

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Baby Herman's scrotum appears normal on inspection.
 A normal scrotum indicates that there are no apparent abnormalities in the scrotal
area, such as swelling, discoloration, or palpable masses.
 This finding suggests that any potential abnormalities related to the penile defect,
such as associated scrotal anomalies or inguinal hernias, are less likely in this case.
 In the context of the described penile defect, a normal scrotum is consistent with
isolated hypospadias.
 Isolated hypospadias refers to cases where the abnormality is limited to the penile
shaft and does not involve the scrotum or other adjacent structures.
 However, it is important to note that a normal scrotum on inspection does not
completely rule out other associated conditions or abnormalities.
 Further assessment and diagnostic tests may still be necessary to evaluate the entire
genitourinary system and ensure a comprehensive evaluation of Baby Herman's
condition.
 The clinical correlation of a normal scrotum helps provide a more focused evaluation
and management approach, highlighting the likelihood of isolated hypospadias and
supporting the need for appropriate consultation and intervention specifically
addressing the penile defect.

Both of Baby Herman's testes are descended and appear normal on palpation.
 The findings of descended testes and normal appearance on palpation indicate that the
testes have properly descended into the scrotum, which is a crucial aspect of normal
male genital development.
 In normal development, the testes typically descend from the abdominal cavity into
the scrotum before or shortly after birth.
 The fact that Baby Herman's testes are descended and appear normal on palpation
suggests that the descent of the testes, a separate process from the penile defect, has
occurred correctly.
 This finding is significant because it helps rule out certain conditions such as
undescended testes (cryptorchidism), where one or both testes fail to descend into the
scrotum. Cryptorchidism is often associated with other genitourinary abnormalities
and can have implications for fertility and hormonal balance.
 The clinical correlation of descended and normal-appearing testes, in conjunction with
the penile defect described, supports the likelihood of isolated hypospadias without
associated abnormalities in the scrotum or testes.
 It provides important information for the healthcare provider in assessing the overall
genitourinary development and planning appropriate management specifically
addressing the penile defect.

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There are no significant abnormalities or complications reported in the patient's
prenatal and labor histories.
 The absence of significant abnormalities or complications during the prenatal period
suggests that there were no known factors or events that could have directly caused
the penile defect, such as maternal infections, exposure to teratogenic substances, or
placental abnormalities.
 This finding indicates that the penile defect is more likely to be a congenital anomaly
rather than a result of prenatal factors.
 Furthermore, the absence of complications during labor implies that there were no
immediate concerns or difficulties in the delivery process that would be directly
related to the penile defect.
 It suggests that the defect was not a result of trauma or injury during birth.
 The clinical correlation of an unremarkable prenatal and labor history supports the
likelihood of isolated hypospadias, where the defect occurs spontaneously during fetal
development without any identifiable external factors playing a significant role.

Baby Herman's parents are concerned about his ability to have sex and conceive when
he grows up due to the penile defect.
 Hypospadias, as described in Baby Herman's case, is a congenital anomaly where the
urethral opening is located on the ventral side of the penis instead of the typical
meatal position at the tip.
 Depending on the severity and location of the defect, hypospadias can affect the
normal functioning of the penis and potentially impact sexual intercourse and
reproductive capabilities.
 The concerns expressed by Baby Herman's parents are understandable, as
hypospadias can pose challenges related to sexual function.
 The abnormal placement of the urinary opening may affect the direction and flow of
urine during urination.
 It can also lead to difficulties with achieving a straight and functional stream of urine.
 Additionally, hypospadias can cause cosmetic and anatomical differences in the
appearance of the penis.
 These differences may affect self-esteem, body image, and psychological well-being, In
terms of fertility, the ability to conceive naturally can be affected in severe cases of
hypospadias, particularly when there are associated abnormalities in the testes or the
reproductive tract.
 The exact impact on fertility varies depending on the severity and extent of the
hypospadias and any concurrent reproductive abnormalities that may be
present.potentially impacting sexual confidence and interpersonal relationships in the
future.

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 It is important to note that while hypospadias can pose challenges, advances in
surgical techniques and interventions have led to successful outcomes in the majority
of cases.
 Many individuals with hypospadias can achieve satisfactory sexual function and have
the potential to father children through various assisted reproductive techniques if
needed.

GUIDE QUESTIONS

1. What are the steps of genital duct differentiation in males and females?

Male Genital Duct Differentiation

Bipotential Stage
 Initially, the undifferentiated fetal gonads have the potential to develop into
either testes or ovaries.

Testicular Determination
 The presence of the Y chromosome in males triggers the differentiation of the
gonads into testes.

Testosterone Production
 The developing testes produce testosterone, which promotes the development
of male internal genital structures.

Wolffian Duct Development

 The presence of testosterone stimulates the development of the Wolffian
ducts, which give rise to the epididymis, vas deferens, and seminal vesicles.

Mullerian Inhibition
 Another substance called Mullerian inhibiting substance (MIS), produced by
the testes, causes regression of the Mullerian ducts, which would otherwise
develop into the female internal genital structures.

Formation of Male Genitalia

 Testosterone also influences the development of the external male genitalia,
including the penis and scrotum.

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 Female Genital Duct Differentiation

Bipotential Stage
 Similar to males, the fetal gonads in females have the potential to develop into
either testes or ovaries.
Ovarian Determination
 In the absence of the Y chromosome and the SRY gene, the gonads
differentiate into ovaries.
Absence of Testosterone and MIS
 Without testosterone or Mullerian inhibiting substance, the Wolffian ducts
regress, and the Mullerian ducts develop into the female internal genital
structures, including the fallopian tubes, uterus, and upper part of the vagina.
Formation of Female Genitalia
 In the absence of testosterone, the external female genitalia, including the
labia, clitoris, and vaginal opening, develop.

2. What are the steps of external genitalia development in males and females?

Male External Genitalia Development

Bipotential Stage
 During early fetal development, the external genitalia are initially
undifferentiated and have the potential to develop into either male or female
structures.
Testicular Determination
 The presence of the Y chromosome and the SRY gene in males leads to the
development of testes.
Testosterone Production
 The developing testes produce testosterone, which is crucial for the
differentiation of male external genitalia.
Formation of the Phallus
 Testosterone promotes the growth and elongation of the genital tubercle,
which eventually forms the penis.
Urethral Fold Fusion
 The urethral folds, located on either side of the developing penis, fuse in the
midline to form the penile urethra.
Closure of Urogenital Folds
 The urogenital folds, located ventrally to the urethral folds, fuse together and
enclose the urethra, forming the penile shaft.

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 Scrotal Formation
 The labioscrotal swellings on either side of the urogenital folds fuse and give
rise to the scrotum.

Female External Genitalia Development

Bipotential Stage
 Similar to males, the external genitalia in females are initially
undifferentiated and have the potential to develop into either male or female
structures.
Absence of Testicular Determination
 In the absence of the Y chromosome and the SRY gene, the undifferentiated
gonads develop into ovaries.
Absence of Testosterone
 Without testosterone, the genital tubercle in females does not elongate as it
does in males.
Formation of the Clitoris
 The genital tubercle develops into the clitoris, a smaller and less elongated
structure compared to the penis.
Urethral Fold and Labioscrotal Swelling Development
 The urethral folds in females do not fuse as they do in males, resulting in the
formation of the labia minora.
 The labioscrotal swellings do not fuse and develop into the labia majora.

3. Discuss hypospadias.

 Hypospadias is a congenital condition that affects the development of the male

external genitalia, specifically the urethral opening.
 In individuals with hypospadias, the opening of the urethra is located on the ventral
side of the penis, rather than at the tip of the penis (meatus), which is the normal
anatomical position.

Types and Severity

 The severity is classified based on the location of the urethral opening.
 The three main types are:

Distal Hypospadias
 The urethral opening is located near the tip of the penis.


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 Midshaft Hypospadias
 The urethral opening is along the shaft of the penis.

Proximal Hypospadias
 The urethral opening is closer to the base of the penis or even within the
scrotum or perineum.

 In some cases, hypospadias may be associated with other congenital anomalies, such
as undescended testes (cryptorchidism), inguinal hernias, or abnormalities of the
foreskin.
 It is important to evaluate the patient for any additional abnormalities and to address
them accordingly.
 The exact cause of hypospadias is not fully understood, but it is believed to be a
combination of genetic and environmental factors.
 Hormonal imbalances during fetal development, exposure to certain medications or
chemicals, and genetic mutations have been implicated as possible contributing
factors.
 Hypospadias is typically diagnosed during a physical examination of the newborn's
genitalia.
 The position of the urethral opening is noted, and the severity is assessed.
 Further evaluation, including imaging studies and hormonal testing, may be
conducted to assess associated abnormalities and determine the optimal management
approach.
 The main treatment for hypospadias is surgical repair, usually performed during early
childhood (typically between 6 and 18 months of age) but can vary depending on the
severity and surgeon's preference.
 The goal of surgery is to correct the positioning of the urethral opening, improve the
appearance of the penis, and ensure normal urinary function.
 The surgical technique used depends on the severity and location of the hypospadias.
 With appropriate surgical management, the outcomes for individuals with
hypospadias are generally favorable.
 Most individuals can achieve normal urinary function and satisfactory cosmetic
results.
 However, follow-up care is necessary to monitor for any complications, ensure proper
growth and development, and address any ongoing concerns related to sexual function
and fertility in adolescence and adulthood.




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4. What abnormalities of genital duct differentiation can affect females?

Persistent Mullerian Duct Syndrome (PMDS)

 In PMDS, there is incomplete regression of the Mullerian ducts, which are
responsible for the development of the fallopian tubes, uterus, and upper part
of the vagina.
 This leads to the presence of both male and female reproductive structures in
individuals with male chromosomes (XY). They may have a uterus and
fallopian tubes despite appearing externally as males.

Androgen Insensitivity Syndrome (AIS)

 AIS is a condition where individuals with male chromosomes (XY) have
partial or complete insensitivity to androgens (male hormones).
 Due to the inability of cells to respond to androgens, the external genitalia do
not virilize, resulting in a female appearance.
 Internal structures such as the uterus and fallopian tubes are typically
absent, and there may be testes present in the abdomen or inguinal region.

17-Beta Hydroxysteroid Dehydrogenase Type 3 Deficiency (17β-HSD3 Deficiency)

 This is an enzyme deficiency that affects the conversion of androgens to
estrogen.
 It can result in varying degrees of masculinization of the external genitalia in
individuals with female chromosomes (XX).
 The severity of masculinization can range from mild clitoral enlargement to
more significant ambiguity of the genitalia.

Congenital Adrenal Hyperplasia (CAH)

 CAH is a group of genetic disorders characterized by a deficiency in enzymes
involved in cortisol synthesis.
 The most common form, 21-hydroxylase deficiency, can lead to excess
production of androgens, causing virilization of the external genitalia in
affected females.
 The degree of virilization can vary, ranging from mild clitoromegaly to severe
fusion of the labioscrotal folds.

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 Ovotesticular DSD
 Formerly known as True Hermaphroditism
 Ovotesticular DSD is a rare condition where individuals have both ovarian
and testicular tissue.
 The external genitalia may exhibit ambiguous or atypical features, such as an
enlarged clitoris or an enlarged phallus with a urethral opening along the
ventral aspect.
 The internal reproductive structures may also be abnormal or combined.

PATHOPHYSIOLOGY

 During fetal development, the differentiation of the male external genitalia is

influenced by hormonal signaling.
 Testosterone, which is produced by the developing testes, plays a crucial role in
promoting the development of male genital structures.
 Insufficient levels of testosterone or alterations in the sensitivity of the target tissues
to androgens can contribute to the development of hypospadias.
 The fusion of the urethral folds is a critical step in the formation of the penile urethra.
In hypospadias, the fusion process is disrupted, leading to an incomplete closure of the
urethral groove.
 This incomplete fusion can result in the urethral opening being located on the ventral
side of the penis, rather than at the tip.
 The genital tubercle is a precursor to the penis.
 In hypospadias, there may be inadequate growth and elongation of the genital
tubercle, resulting in an underdeveloped penis.
 The exact mechanisms underlying this growth deficiency are not fully understood but
likely involve disruptions in hormonal signaling and genetic factors.
 Hypospadias has been associated with various genetic abnormalities and mutations,
although specific genes involved in the pathogenesis have not been fully identified.
 Studies have suggested that alterations in genes related to androgen metabolism,
androgen receptor signaling, and urethral development may contribute to the
development of hypospadias.
 However, the genetic component of hypospadias is complex, and the interplay between
multiple genes and environmental factors remains a subject of ongoing research.
 In addition to genetic factors, exposure to certain environmental factors during fetal
development has been implicated in the pathogenesis of hypospadias.
 Endocrine-disrupting chemicals (EDCs), such as phthalates and pesticides, have been
suggested as potential contributors.
 These can interfere with hormonal signaling and disrupt normal genital development.

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 RISK FACTORS

Genetic Factors
 There is evidence to suggest a genetic predisposition to hypospadias.
 Having a family history of hypospadias or other genital abnormalities increases the
risk of a child being born with the condition.
 Specific gene variants and mutations related to androgen metabolism, hormone
receptors, and urethral development have been implicated in some cases of
hypospadias.

Maternal Age
 Advanced maternal age (over 35 years) has been associated with a higher risk of
hypospadias.
 The reasons for this association are not entirely clear, but it is thought that age-related
changes in hormonal regulation or other genetic factors may play a role.

Maternal Exposures
 Prenatal exposure to certain environmental factors and medications has been linked
to an increased risk of hypospadias.
 These include exposure to endocrine-disrupting chemicals (EDCs) such as phthalates,
pesticides, and certain medications used during pregnancy.
 EDCs can interfere with hormonal signaling and disrupt normal genital development
in the fetus.

Low Birth Weight and Prematurity

 There is an increased risk of hypospadias in infants born with low birth weight or born
prematurely.
 The underlying mechanisms are not fully understood, but it is believed that factors
related to incomplete development of the genital structures during the fetal period
may contribute to this association.

Maternal Medical Conditions

 Certain maternal medical conditions, such as diabetes and obesity, have been
identified as potential risk factors for hypospadias.
 It is hypothesized that these conditions may affect hormonal regulation or placental
function, leading to altered fetal development.

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Assisted Reproductive Technologies (ART)
 Some studies have suggested a higher incidence of hypospadias among infants
conceived through assisted reproductive technologies, such as in vitro fertilization
(IVF).
 The reasons for this association are not well understood, but factors related to the ART
procedures or the underlying infertility may play a role.

TREATMENT AND MANAGEMENT

Surgical Repair
 The primary treatment for hypospadias is surgical repair, typically performed during
early childhood.
 The goal of surgery is to reposition the urethral opening to the tip of the penis
(meatus) and create a straight, functional urinary stream.
 The specific surgical technique used depends on the severity and location of the
hypospadias.
 In distal hypospadias, where the urethral opening is near the tip of the penis, a simple
repair technique may be employed, such as the Snodgrass or Mathieu procedure.
 In more severe cases, such as midshaft or proximal hypospadias, more complex
procedures like the tubularized incised plate (TIP) or staged repairs may be required.

Timing of Surgery
 The timing of surgery depends on various factors, including the severity of
hypospadias, the child's overall health, and the surgeon's preference.
 Surgery is typically performed between 6 and 18 months of age, although the optimal
timing may vary in individual cases.

Multidisciplinary Approach
 The management of hypospadias often involves a multidisciplinary team consisting of
pediatric urologists, pediatric surgeons, and other specialists.
 This collaborative approach ensures comprehensive evaluation, surgical expertise,
and long-term follow-up care.

Preoperative Evaluation
 Before surgery, a thorough evaluation is conducted to assess the child's overall health,
the extent and severity of hypospadias, and any associated abnormalities.
 This may include imaging studies, hormonal testing, and evaluation of urinary
function.

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Follow-up Care
 After surgical repair, regular follow-up visits are necessary to monitor the healing
process, assess urinary function, and evaluate the cosmetic outcomes.
 Long-term follow-up care continues into adolescence and adulthood to address any
concerns related to sexual function, fertility, and potential complications.

Psychological Support
 It is important to provide psychological support to the child and their family
throughout the treatment process.
 Hypospadias can have emotional and social implications, and counseling or support
groups can help address any concerns or challenges that may arise.

MUST KNOW

Hypospadias
 Results when the distal urethra does not develop appropriately and the urethral
meatus is found anywhere along the ventral surface in the midline of the penile
shaft, scrotum, or perineum.
 It is the most common congenital anomaly of the penis.

Chordee
 Curving of the penis

Uterus Arcuatus
 The uterus is only slightly indented in the middle

Uterus Didelphys
 The uterus, cervix, and sometimes vagina are duplicated entirely.

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