1. Dr.renuka

2.  When the external genitalia do not have the
typical anatomic appearance of normal male or
female genitalia, the condition is known as
ambiguous genitalia.
 This condition can be caused by various
disorders of sexual differentiation or intersex
disorders.

6.  DSDs have been defined as “congenital conditions
in which development of chromosomal, gonadal,
or anatomic sex is atypical” .
 Female pseudohermaphrodites (46,XX DSD)-
have a female genotype and two ovaries for
gonads, but their external genitalia show a
variable degree of virilization- Virilised female
 Male pseudohermaphrodites (46,XY DSD)- have
a male genotype and two testes for gonads, but
their external genitalia show a variable degree of
feminization-undervirilized male


7.  True hermaphrodites (ovotesticular DSD) have
both testicular and ovarian tissues in the gonads .
 In patients with pure gonadal dysgenesis (PGD),
both gonads are streak gonads (ie, dysfunctional
gonads without germ cells).
 Patients with mixed gonadal dysgenesis (MGD)
have a testis on one side and a streak gonad on the
other

8.  chromosomal basis for sex is determined at conception.
 The internal and external genital structures remain
undifferentiated for up to 6 weeks gestation.
 After approximately 6 weeks gestation, the genital ridge
becomes one of the gonads, either an ovary or a testis.
 Three important precursor components of the genital system
are the1. germ cells,
2. genital ridge,
3. two sets of internal sex ducts, namely, the
müllerian-paramesonephric ducts and the wolffian-mesonephric
ducts

9.  Testicular development is guided by testis
determining factor , which is encoded by the SRY
gene located on the short arm of the Y
chromosome.
 Under the influence of testis determining
substance, germ cells in the genital ridge
differentiate into Sertoli cells, which secrete
müllerian inhibiting substance (MIS) , and Leydig
cells, which produce testosterone

10.  MIS causes complete regression of the müllerian
ducts
 Testosterone promotes maturation of
spermatogonia and regulates development of the
male phenotype by means of paracrine and
endocrine actions.
 By means of paracrine action, the wolffian duct
develops into the epididymis, vas deferens,
ejaculatory duct, and seminal vesicles.

11.  In the absence of the Y chromosome, gonads
differentiate into ovaries at around 11–13 weeks
gestation.
 Ovarian hormones are thought to play no role in
female phenotype differentiation.
 Absence of MIS leads to persistence of müllerian
structures, which develop into the fallopian tubes,
uterus, cervix, and upper vagina.
 Because of the absence of testosterone, the
wolffian ducts involute.

12.  Undifferentiated external genitalia include the
urogenital tubercle, urogenital swelling, and
urogenital folds.
 The stimulation of dehydrotestosterone,
converted from testosterone by the action of 5α-
reductase, causes these structures to develop in
males into the glans penis, scrotum, and penile
shaft, respectively.
 In females, they develop into the clitoris, labia
majora, and labia minora, respectively

16.  Clinical findings
1. overt genital ambiguity ;
2. an apparent male with bilateral nonpalpable testes
(full-term infant), micropenis, hypospadias
associated with separation of the scrotal sac , or an
undescended testis with mild hypospadias;
3. an apparent female with clitoral hypertrophy of
any degree, a foreshortened vulva with a single
opening, or an inguinal-labial hernia containing a
gonad

17. 4. a family history of DSD (eg, complete
androgen insensitivity [CAI] syndrome [also
known as Morris syndrome]);
5. a discordance between genital appearance and a
prenatal karyotype

18. 1.Karyotyping
2.Imaging (US, genitography, MR imaging)
3.Determination of bone age (advanced maturation in
CAH)
 Determination of hormone levels
1. 17-hydroxy-progesterone level (normal = <5nmol/L,
elevated = >100 nmol/L
2. Testosterone level: reduced in inborn errors of
testosterone biosynthesis or elevated in 5a-reductase
deficiency and androgen receptor insensitivity (MPH)

19. HCG challenge test (shows if functioning testicular
tissue is present)*
MIS level in blood
Gonadotropin levels in blood: elevated levels
suggest insufficient production of testosterone
and MIS
 Endoscopy, laparoscopy before surgery

20.  Imaging plays an important role in depicting the
internal organs and urogenital anatomy in children
with ambiguous genitalia.
 US is the prima modality for evaluation of the
internal reproductive organs,
 genitography and voiding cystourethrography are
used for evaluation of urethral and vaginal tracts and
fistulas.
 MR imaging may serve as a problem-solving
modality for clarifying the internal anatomy and
searching for internal gonads.

21.  US is the primary modality for establishing th
presence or absence of gonads and müllerian
derivatives.
 It can be performed quickly and does not involve
radiation or sedation.
 A US examination should include the inguinal,
perineal, renal,and adrenal regions.
 The uterus and ovaries ar relatively easy to find at
US performed in the neonatal period, since these
structures are prominent under the influence of
maternal harmones

22.  The causes of female pseudohermaphroditism
(46,XX DSD) include CAH and transplacental
androgen exposure.
 CAH is the most common cause of ambiguous
genitalia .
 It manifests as various degrees of virilization in
girls and as precocious puberty in boys.
 Most cases are secondary to 21-hydroxylase
deficiency. An elevated 17-hydroxy- progesterone
level indicates the diagnosis of CAH

24. Adrenal glands with a limb over 20 mm long and 4
mm wide and with normal corticomedullary
differentiation are suggestive of CAH
 Some authors believe that it is not just the size of
the gland but a combina-tion of its size,
echogenicity, and surface contour that helps make
the diagnosis of CAH.
 Al-Alwan et al found that a combination of a lim
width greater than 4 mm, a lobulated surface, and
stippled echogenicity had a sensitivity of 92% and
a specificity of 100% in making the diagnosis

25.  The presence of normal-sized adrenalglands does
not exclude the diagnosis of CAH cerebriform
appearance of the adrenal glands is reportedly
specific for CAH .
 A normal uterus and ovaries are seen at US in
female pseudohermaphroditism.
 Some boys with CAH may present with
intratesticular nodularity (hyperplasia of Leydig
cells).

27.  Male pseudohermaphroditism (46,XY DSD)
may manifest as a female phenotype with
various degrees of under virilization secondary
to partial androgen insensitivity.
 In CAI syndrome, there is no ambiguity, and
the XY fetus is born with a female phenotype,
with the diagnosis usually made at puberty
during work-up for amenorrhea

28.  Testes may be found in the inguinal canal or
abdomen.
 If testicular tissue is not seen at US, it should be
sought with MR imaging or laparoscopy in view of
the increased risk of malignancy.
 Other imaging features of male
pseudohermaphroditism include absence of the
uterus and ovaries in the pelvis.
 Isolated abnormal MIS production in otherwise
normal testes results in a male phenotype-genotype
with müllerian structures, a condition known as
persistent müllerian duct syndrome

30.  The characteristic imaging feature of true
hermaphroditism is the presence of an
ovotestis or of one testis and one ovary in the
same patient
 An ovotestis may be seen as a structure with a
combination of testicular echotexture and
follicles

31.  Gonads with a normal ovarian and testicular
appearance at US may prove to be ovotestes at
histologic analysis
 . The uterus is almost always present in
ovotesticular DSD.

33.  The presence of a testis on one side and a streak
gonad on the other establishes the diagnosis of
MGD.
 Streak gonads are difficult to visualize and
characterize at imaging, including US and MR
imaging.
 A gonad with the morphologic appearanc of a
testis or ovary at US may prove to be a dysgenetic
gonad at biopsy .
 At minimum, a rudimentary uterus or fallopian
tube can be seen on the side with the streak gonad.
On the side with the testis, local MIS diffusion
prevents development of a fallopian tube (

35.  PGD manifests as bilateral dysgenetic gonads with
underdeveloped müllerian derivatives.
 There is usually no genital ambigui ty, and the
phenotype is female from birth
PGD is often confused with CAI syndrome, since
patients present at puberty with failure of menarche
and a female phenotype .
 In PGD, there are usually normal or hypoplastic
müllerian derivative because the dysgenetic gonads
often do not produce MIS, whereas in CAI syndrome
there are no müllerian derivatives.

36.  In patients with DSD, genitography demonstrates
a male or female type urethral configuration and
any fistulous communication with the vagina or
rectum.
 Many patients have persistent urogenitalsinus,
and an adequate genitogram should help identify
the exact location where the urethra and the
vagina are joined.
 These anatomic characteristics are very important
for mapping surgical strategy.
 Genitography shows the presence or absence of
the vagina, its relationship to the urethra, the level
of the external sphincter, and cervical impression.

37.  It is important to examine all perineal orifices
and insert the catheter fo a short distance into
each orifice to preserve its morphologic
appearance
 .A good maneuver is to fill the balloon of an 8-
F Foley catheter outside the body and insert
just the distal tip, performing a retrograde
injection

38.  A urogenital sinus is the embryologic precursor
of the bladder, urethra, and prostate gland in
males and of the bladder, urethra, and distal
third of the vagina in females.
 It is formed from the anterior part of the cloaca.
 Urogenital sinus malformation in females leads
to the urethra and vagina opening through a
single aperture.
 This can result from excessive androgen
exposure in utero (eg, CAH), which also leads to
virilization of the external genitalia.

39.  The presence of hydrocolpos or
hydrometrocolpos and ambiguous genitalia
with only two perineal orifices (one of which is
the anus) confirm the presence of a urogenital
sinus malformation resulting from virilization

41.  T1- and T2-weighted MR imaging sequences,
with their multiplanar capability and superior
tissue characterization, can provide detailed
anatomic information.
 In one study, MR imaging was found useful in
the evaluation of ambiguous genitalia, with
depiction of the uterus in 93% o cases, the
vagina in 95%, the penis in 100%, the testes in
88%, and an ovary in 74%

42.  MR imaging and US are considered equally
sensitive in the evaluation of intrapelvic
structures.
 MR imaging is more sensitive than US in the
evaluation of the gonads but is still not
completely reliable for excluding intraabdominal
gonads.
 Ectopic gonads, testes, and noncystic immature
ovaries have intermediate signal intensity on T1-
weighted MR images and high signal intensity
with an intermediate-signal-intensity outer rim
on T2-weighted images

43.  Streak gonads are difficult to detect and can be
seen as low-signal-intensity stripes on T2-
weighted images .
 High-signal-intensity foci in streak gonads
could represent neoplastic change

44.  Clitoral hypertrophy in XX DSDs can be
differentiated from the penis at MR imaging on
the basis of absent or poorly developed
supporting penile structures such as the
bulbospongiosus muscle and posteriorly
located transverse perinei muscles
 . Renal and adrenal evaluation can be
performed as part of the same MR imaging
examination with an extended field of view.

48.  Because 20%–30% of children with XY PGD and
15%–20% with MGD develop a gonadal neoplasm
within the 1st or 2nd decade of life streak gonads
should be removed .
 The presence of a well-defined part of the Y
chromosome (GBY [gonadoblastoma locus on the
Y chromosome]) is implicated in the development
of malignant neoplasms in dysgenetic gonads

49.  Gonadoblastoma is the most commo tumor,
usually arising from dysgenetic intraabdominal
gonads , and is considered to be a precursor to
the development of type II germ cell tumors
seen in these patients
 Type II germ cell tumors include (a)
seminomatous tumors such as seminoma and
dysgerminoma, and (b) nonseminomatous tumors
such as embryonal carcinoma and
choriocarcinoma.

50.  The presence of an echogenic focus at US
associated with the pelvic organs or found in
ectopic gonadal tissue within the inguinalcanals
or labioscrotal folds should be regarded with
suspicion, since gonadoblastomas often calcify.

51.  There is increased risk of developing Wilms
tumor, particularly when XY gonadal
dysgenesis is associated with glomerulopathy
in Drash syndrome.
 The average patient age at the time of
development of Wilms tumor in Drash
syndrome is 3 years.
 Screening for Wilms tumor with renal US every
6 months to 1 year up to school age has been
recommended in children with dysgenetic
gonads

52.  It is vital that a child with ambiguous genitalia be
evaluated by a multidisciplinary team (including a
radiologist and other pediatric experts) using a
coordinated approach to arrive at a timely diagnosis so
that proper gender assignment can be made early in life
 Imaging plays an important role in demonstrating organs.
 US is the preferred modality for initial evaluation.
 Genitography is used to assess the urethra, vagina, any
fistulous connections, and complex tracts.
 MR imaging can serve as a problem-solving modality that
can clearly depict the genitalia and gonads