Definition of IntersexDefinition of Intersex
It is incomplete (imperfect )sexual
differentiation into either male or
(doubt on sex assignment).
Genotype of embryo 46XX or 46XY is
established at fertilization
SRY (sex-determining region on Y) that
encodes a protein called testis-
determining factor (TDF) are responsible
for male differentiation
Sertoli cell AMH
lydeig cell testosterone
Components which form female and
male reproductive systems are:
1. Gonads Ovaries or testes
2. Genital Duct Systems
Mesonephric and Paramesonephric ducts
3. External Genitalia
Components which form female and male
reproductive systems are:
Indifferent EmbryoIndifferent Embryo
Weeks 1-6 sexually indifferent or
Week 7 begins phenotypic sexual
Week 12 female or male characteristics of
external genitalia can be recognized and
completed at 20 weeks.
At 4At 4THTH
Week of gestationWeek of gestation
extending from the
to the cloaca
At 5At 5THTH
Week of gestationWeek of gestation
A Swelling on
either side of
on medial side of
duct forms the
Female Genital Duct FormationFemale Genital Duct Formation
In ovary the absence of testosterone
inhibits the development of the
In absence of AMH, paramesonephric
ducts form the female internal genital
At 6At 6THTH
week gestationweek gestation
or Mullerian Duct
develops lateral to
”wolffian “ Duct
The middle and caudal parts of
the Mullerian ducts undergoes
medial migration and fusion.
The cranial 1/3 → tubes.
The middle 1/3 → uterus and
Caudal 1/3 → upper 3/4 of
Development of the vaginaDevelopment of the vagina
Seven points of sex identificationSeven points of sex identification
1. Genetic sex
2. Gonadal sex
3. Sex of the duct system
4. External genital sex
5. Phenotypic sex
6. Gender sex (cerebral one)
7. Sex of rearing
Normal sex differentiationNormal sex differentiation
depends on.depends on.
The delicate interplay of
-And psychic factors.
Klinefelter syndromeKlinefelter syndrome
A male with an extra X chromosome, so
the karyotype is 47 ,XXY.
Some patients have more than 2 X
chromosomes, and some have a mosaic
karyotype (47 ,XXY -46,XY).
The extra X chromosomeThe extra X chromosome
may lead to somaticmay lead to somatic
1) Gynaecomastia (90%).
2) Female distribution of
3) Mental retardation
which increases with the
increase in number of X
Mixed gonadal dysgenesisMixed gonadal dysgenesis
The individual is a female. The Karyotype is
There is one testis on one side and a streak
gonad or no gonad on the other side.
The external genital organs may be ambiguous,
and the patient virilizes at puberty.
The individual has both testicular and
ovarian tissues in different combinations.
An ovary on one side and a testis on the
other side, or an ovary or testis on one
side and an ovotestis on the other side,
or an ovotestis on both sides.
The true hermaphrodite
The true hermaphroditeThe true hermaphrodite
The sex chromosomes may be male (XY)
or female (XX) ormosaic, i.e. some cells are
XX and others are XY.
The external appearance (phenotype) may
be male or female.
The external genital organs may be male
or female or ambiguous.
Diagnosis is made by gonadal biopsy.
pseudo hermaphroditepseudo hermaphrodite
gonads belong to one sex and the external
genital organs belong to the other sex.
If the gonads are ovaries the individual is a
female pseudohermaphrodite, e.g. congenital
If the gonads are testes the individual is a male
pseudohermaphrodite, e.g. testicular
What is Congenital Adrenal HyperplasiaWhat is Congenital Adrenal Hyperplasia
(CAH) is a family of inherited disorders affecting the
Autosomal recessive (mutation of chromosome 6 21-
hydroxylase enzyme impairment)
Commoner in consanguineous marriage
It is due to failure of synthesis of cortisol from 17a-
hydroxyprogesterone due to deficiency of certain
enzymes mostly 21-hydroxylase enzyme (95%) and
occasionally 11 beta-hydroxylase.
Adrenal Cortex Hormone SynthesisAdrenal Cortex Hormone Synthesis
Types of CAHTypes of CAH
1. 21-hydroxylase deficiency (>90%)
Classical - salt wasting(75%; 1 in 15,000)
- simple virilizing (25%; 1 in 60,000)
Nonclassic (1 in 1,000)
11B-hydroxylase deficiency(3-5 %, 1 in 100,000)
17α-hydroxylase deficiency / C 17 lyase deficiency
3B-hydroxysteroid dehydrogenase deficiency(1%)
Failure to produce cortisol leads to increased
production of ACTH, which leads to
hyperplasia of the adrenal cortex and
increased production of androgens from 17a-
There is virilization of the female fetus with
enlargement of the clitoris, fusion of labia
minora, and hirsutism.
The fallopian tubes, uterus, and vagina are
present but remain infantile.
Clinical ManifestationClinical Manifestation
Cortisol deficiency – hypoglycemia, inability to withstand
stress, vasomotor collapse, hyperpigmentation,, muscle
weakness & fatigue.
Aldosterone deficiency – About 75% of infants have
hyponatraemia and hyperkalaemia (salt-losing), due to
decreased synthesis of aldosterone
Androgen excess – ambiguous genitalia, virilization of
external genitalia , hirsutism,
*Late onset CAH – normal genitalia, have acne, hirsutism,
Karyotyping (determine sex chromosome)
Abdominal Ultrasound – to detect presence
of uterus, cervix and vagina.
Dexamethasone for life to suppress fetal ACTH-
induced androgen production can
reduce/eliminate ambiguity of external genitalia
in affected female fetuses
Surgical correction of the external genitalia is
carried out, preferably during the first 2 years of
life to avoid psychological injury of the child.
CYP21 genotyping can be performed in a family
with history of CAH