Download 5-INTERSEXT

1.Will be able to understand how the sex of
each individual is determined .
2. To know which abnormalities in sex
determining factors that will result in
intersex.
3. Will be able to understand how these
abnormalities are presented clinically at
birth, during childhood and adolescence
4. Will be able to reach to the diagnosis of
different cases of intersex and how to
manage them
The
effect of sex chromosome on the
undifferentiated gonads
The
The
proper function of the differentiated gonads
response of the end organs to testicular
activity
They determine the final functional morphology of the
undiff. Gonads by the following:
1.Presence of Y chr. In association with one or more X
chr. the gonads develop into testis
2.If more than X chr. present with Y chr. ,the
gonads
differentiation to testis is
normal during I.U life
but testicular develop.
during puberty is impaired
3.If tow or more X chr. Are present without Y chr. the
undiff. Gonads will develop into ovary.
4.If more than tow X chr.present the subsequent
ovarian develope. During puberty is impaired.
The presence of Y chr. Will promot testicular
diff .
through TDF ,the gene of which
present
on the short arm of chr.
TDF regulate H-Y Ag whose gene present on
Y
chr. or outosome.
H-Y Ag is a plasma mem. Protein & is widely
distributed in cells.
During IU life the presence of functioning testis will result in
male phenotype
Absence or presence of non functioning testis will always
lead to a female phenotype whether ovaries are
present or not. So male develop. Is the result of
presence of testis & female develop. Is the result of
absence of testis
This function of testis during IU life is through secretion of
2
substances which are :
1. testosterone from Leidg cells
2.MIF from Sertoli cells . It is aglycoprotein & it has a
unilateral action & Mullerian structures are sensitive
to it only during the first 8 weeks of gestation
Testosteron secreted from testis will initiate
develop. of male ext. & int. genital
structures
The Wolfian structurs are able of utilizing
test. directly while ext. genitelia utilize
test. After conversion to
dihydrotest. By
5α reductase enz.
For effective utilization both hormones , it is
necessary
for test. to be bound to receptors in the
cytoplasm of
cells .
So ineffective binding will lead to abnormal
sexual
develop.
1.Abnormality in sex chr. which interfer with testicular
develop the only common one is 45 XO/46 XY
mosaism leading to one form of gonadal dysgenesis.
2.Testis may be unable of producing testosterone either
because of anatomical or enzymatic testicular failure.
3.The end organ may be unable of utilizing testos.
because of 5α reductase deficiency or failure of
testost. binding(androgen insensitivity).
4.The production of MIF may be deficient leading to the
growth of Mullerian system in a male.
5.In a genetic female (46 X X) musculinization of
ext. genitalia may result in excessive androgen
production as in congenital adrenal hyperplesia or from
androgen from other sources.
6.Rarely in agenetic female, the gene capable of
production of H-Y Ag may be found on an autosome
leading to 46 XX male
7.True hermaphrodite i.e the presence of testicular &
ovarian tissue in the same individual
The childe with ambigouos genitalia may present
in a number of ways:
1.Musclinized female
2.Under musclinized male
3.True hertmaphrodite3
When the condition discovered at neonatal period the
first
diagnosis to be confirmed is that of CAH
because it is a correctable condition and the baby
may die if it is of salt loosing type
So when a childe or neonate presented with ambiguous
genitalia ,we should look for the presence of testis up
to
the inguinal area and the first concern is to
exclude a
musclinized female ( CAH or excessive
androgen).
If these causes had been excluded, then the diagnosisis
either an undermusclinized male or true
hermaphrodite
It is the most common cause of female intersex
,and it
is an autosomal recessive disorder
which is due to
enzymetic deffect.
The commonest is 21 hydroxylase defficiency
90%
&less commonly is 11β hydroxylase
defficiency
linical features
1. clitoral hypertrophy.
2. Excessive fusion of labia minora which obscure
the vagina & urethra forming an artificial
urogenital sinus which has an opening on
the perineum near the base of clitoris.
3.Thickining of labia majora which may resemble
scrotum of testis
4.The uterus ,fallopian tubes & vagina are present
which open in the urogenital sinus.
5. In some infant ,a dangerous salt loosing
syndrom may arise due to associated
aldosteron defficiency and the infant may
die from wasting and vomiting within few
weeks of life if the diagnosis is delayed
So when a neonate or infant preset with ambiguous
genitalia , the initial exam. don to identify the
presence or absence of testis . If they are absent then
the diag. of CAH is raised & the following investg.
should be done:
1. Karyotyping on a sample of cord blood.
2. Measurement of 17 α hydroxyprogesteron in blood
increase .
If this I not available then measurement of
pregnantriol in
urine is done.
3.Measurement ofandrogen level in urine by assaying
urinary
17 oxosteroid.
4.Electrolyt level in serum , if salt loosing syndrome
present
then Na &Cl are low and K is elevated.
5. Pelvic U/S to confirm the presence of uterus& vagina
Should be
immediate:
1.Cortizol or corticosteron to suppress ACTH.
2.In salt loosing type ,correction of elect. defect.
3.Surgical correction of ext. genitalia in the form of:
A. Reduction in the size of clitoris
this is better done during neonatal period & is
either by amputation or by reduction
clitoroplasty.
B. Division of the fussed labial folds in order to
expose the vagina and urethra.
this op. don at any age at the same time of op.
& it may need to be repeated later during
puberty
Those patient can achieve normal menses &
fertility but
usually the menarche is delayed 2
years specially in
those with inappropriate
hormonal control
Some patients may be presented with menstrual
irregularity as oligomenorrhea , amenorrhea or
even infertility specially in salt loosing type
1. Causes of interesex at birth &
infancy.
2. Clinical presentation of intersex
after infancy & causes
1. Androgen secreting tumor during pregnancy e.g
androblastoma
2. The use of progestationl drugs that have
androgenic
effect
3.Idiopathic
The presentation of neonate or child is the same
for CAH & no other metabolic defect
The management initially is to exclude CAH and if
this is excluded , the treatment should be in the
form of surgical correction as in CAH
If musclinization of a genetic female from excessive
androgen had been excluded then distinction most be
made bet. An undermusclinized male & tre
hermaphrodite.
The distinction can be made only by laparotomy &
gonadal biopsy . Laparoscopic biopsy is not an
adequate procedure for establishing the nature of a
gonad in intersex.
Gonadal biopsy is not don to choose the sex of rearing
,which is don according to the suitability of the ext.
genitalia for sexual life.
But still it is important to know the nature of the gonads
in order to remove the inappropriate tissue for the
chosen sex .
A. Fault in androgen production
1.Anatomical testicular failure:
there may be abnormality in testicular development
& differentiation
The clinical presentation depend on testicular
diffretiation but usualy there is very milde
musclinization of ext. genitalia. The uterus,tubes &
vagina are present (absence of MIF)
Management:
*surgery for reconstruction of ext. genitalia as in
CAH
*Removal of streaks of gonads bec. Of risk of maleg.
*At time of puberty replacement with estrogen
&progesteron for develop.of secondary sex character
& menstruation
2. Enzymatic testicular failure
There is a defect in the biosynthesis of testosterone
and musclinization will depend on the degree of
defect the uterus ,tubes & vagina are absent.
The management will depend on the degree of
musclination but the female role is usually chosen
(surgery with removal of gonads).
B. End organ insensitivity
1. 5α reductase enz. deficiency
There is poor musclinization of ext. genitalia & it is
an autosomal recessive disorder
Conformation of the dig. Is by giving HCG to stimulate
the gonads & measuring testosteron level before &
after treatment .
The management also depend on the degree of
musclinization
If the condition is undiagnosed & the childe is grown up
as a female , at time of puberty & increase in
testosteron production there will be verilization & the
patient may wish to change the sex to amale so
management should be before puberty
2. Androgen insensitivity
If the defect is complete ,then the patient is
normal (normal female ext. genitalia) but at time of
puberty present as primary amenorrhea
If the defect is partial then the presentation would be at
birth with ambiguous genitalia.
The management is as previous with surgery
(reconstruction of ext.genitalia &removal of testis)
with hormonal replacement at puberty).
* This condition is common in South Africa .The presentation vary with
varying degree of ambiguity but usually uterus, tubes and vagina are
present.
* The karyotype in most cases is that of 46 XX, the next common is 46 XX/
46 XY then 46 XY.
* The distribution of the gonads is that the most frequent is the presence
of ovitestis in one side &an ovary on the other one
* The other common
is the presence of an ovary on one side & a testis on the other
.
* Diagnoses is by gonadal biopsy
* The sex of rearing would be determined according to the functional
capacity of the ext.genitalia after which the inapropperiate gonads are
removed.
* If it is not possible to identify the ovarian tissue from testicular one then
both should be removed & replacemant therapy at puberty is given.
Usually if the condition is not apparent at birth ,the patient
would be presented some years later at time of puberty & the
complain would be
1.Some heterosexual features become evident
2.Pre-existing minor heterosexual features become more
profound.
3.Sometimes intersex is present since childhood but was ignored
& not investigated.
The investigation for such patient would be the same as in
infancy & childhood & only differ minor aspect e.g. in case of
CAH the possibility of salt loosing syndrome is excluded
Another aspect is that in the management we should consider
the type of sex that the patient been adjusted to and no
attempt to change it e,g, patient with androgen insensitivity.
It is most likely to be evident for the first time at or
after puberty but may be discovered earlier during
childhood (complete insensitivity).
The presentation at puberty is that of primary
amenorrhea in a female with absence of pubic &
axillary ,normal ext. genitalia but short blind vagina .
The uterus is absent &the testis are found within the
abdomen, in the inguinal canal or within labia. The
karyotype is 46 XY.
Hormonal assay show
*normal testosteron level of male.
*LH is increased due to insensitivity of hypoth. &
pituitary to testosteron.
*FSH level may be slightly raised.
This abnormality is due to the lack of androgen
receptors
The diag. may be made early during childhood when
testis are found within a hernial sac or the presence of
the syndrome in an older sister in the family &
karyotype of 46 XY.
The management will depend on the age of the
patient
If it is at or after puberty then the management is by
removal of the testis (risk of malignancy) & give
hormone therapy (acyclical estrogen because there is
no uterus) .
If the condition discovered during childhood & there is
no obvious heterosexual feature , then removal of
testis may be delayed after puberty to get some
feminizing features , but if there is heterosexual
features then the gonads should be removed at
childhood followed by hormone therapy at puberty &
onward
Surgery may be required for very short vagina in the
form of vaginoplasty or the use of vaginal dilators
Patient with CAH who had been grown as female are
unlikely to have sufficient musclinization of ext.
genitalia , so surgery is not required
Sometimes in cases that had been misdiagnosed since
birth or undiagnosed due to the presence of extreme
musclinization & the childe had been grown as male,
so it is wise to let the patient live as a male but
cortezol should be given ,then the patient would
menstruate(due to decrease in androgen) so total
hysterectomy with oopherectomy is done .
If the deficiency is complete then the diag. is not made
till time of puberty , when the patient who is grown as
a female would have a male type puberty with
verilization.
So the management would depend on the functional
capacity of ext. genitalia but usually the female role is
chosen
The presentation at puberty would depend on the
function of the gonads .e.g. menstruation may occur
at puberty in a hermaphrodite who had been thought
to be a male .So in such cases hysterectomy with
removal of ovarian tissue should be done with
mastectomy if there is breast developement
* 46 XXmale dos not present as intersex but
may have
hypospadias.
* 46 XY male with isolated MIF deficiency also
dos not present as intersex but Mullarian
structures may be found in the abdomen of a
male during laparotomy.