2. What is DSD
• A condition “In which development of chromosomal, gonadal or
anatomical sex is atypical”
• Atypical or ambiguous genitalia- Any case in which the external genitalia
do not appear completely male or completely female
• Standards for genital size dimensions, variations in size of these
structures do not always constitute ambiguity
3. • Physiology of sexual development
• Testis-determining factor differentiation is visible by the 4th week of gestation
XY karyotype XX karyotype
7th week of gestation
Functional Leydig Functional Sertoli cells
9. Diagnostic tests
• 1. Karyotype, with rapid determination of sex chromosomes
( within 24-48 hours)
• 2. Other blood tests:- a- Screen for congenital adrenal hyperplasia: Cortisol
adrenal androgens- 17-hydroxyprogesterone and androstenedione for 21-
hydroxylase deficiency
b- Screen for androgens and their biosynthetic precursors
c- Screen for gonadal response to gonadotropin in patients suspected of
having testicular gonads: stimulation with injections of HCG; measure
testosterone and dihydrotestosterone before and after HCG
d- Molecular genetic analyses for SRY (sex-determining region of the Y
chromosome) and other Y-specific loci
e- Gonadotropin levels
13. 46,XX DSD
• Previously known as female-pseudohermaphrodites
• Most common forms of 46,XX DSD are virilizing forms of congenital
adrenal hyperplasia (CAH)
• Normal ovaries
• Internal female organs are present
• Variable degrees of virilisation of the external genitalia
14. A 6-yr-old girl with congenital virilizing adrenal hyperplasia. The height age was
8.5 yr, and the bone age was 13 yr
15.
16. - Complete masculinisation
- Normal looking
hyperpigmented male
genitalia
(but no palpable testes)
A 46,XX patient known to
have congenital adrenal
hyperplasia due to 21 α-
hydroxylase deficiency
17. Pigmented, short, curved
phallus, central urogenital
slit,
and separated labioscrotal
testis
A 46,XY patient known to
have congenital adrenal
hyperplasia due to 3β-hydroxy
dehydrogenase deficiency
18. - Micropenis
- Underdeveloped scrotum
- Bilateral undescended testes
A 46,XY patient known to have
gonadotrophin hormone
deficiency
19. 5α-Reductase deficiency
Boys with a small phallus
Bifid scrotum
Urogenital sinus with
perineal hypospadias, and a
blind vaginal pouch
20. Androgen Insensitivity Syndromes
Partial androgen insensitivity with
descended testes in bifid labioscrotal folds
Less severe partial androgen insensitivity with
severe hypospadias and maldescent of testes
21. • X-linked recessive disorders is due to mutations in the androgen receptor
gene
• 46,XY chromosomal complement- Phenotypic females (in complete AIS)
to males with various forms of ambiguous genitalia and undervirilization
(partial AIS, or clinical syndromes such as Reifenstein syndrome) to
phenotypically normal-appearing males with infertility
• Presence of testes and normal or elevated testosterone and LH levels are
common to all children
22. • Complete AIS- Extreme form of failure of virilization
• Genetic males appear female at birth
• External genitalia are female, vagina ends blindly in a pouch, uterus is
absent due to normal production and effect of AMH In about one third of
patients, Unilateral or bilateral fallopian tube remnants
• Testes are usually intra-abdominal but may descend into the inguinal canal,
they consist largely of seminiferous tubules
• At puberty normal development of breasts, and the habitus is female, but
menstruation does not occur and sexual hair is absent.
• Adult heights of these women are commensurate with those of normal
males despite profound congenital deficiency of androgenic effects
23. • Normal male levels of testosterone and DHT
• Failure of normal male differentiation during fetal life
• Defective response to androgens, absence of androgenic effects is caused by a
striking resistance to the action of endogenous or exogenous testosterone at the
cellular level
• Partial AIS- Perineoscrotal hypospadias, bifid scrotum, and cryptorchidism to
extreme under virilization appearing as clitoromegaly and labial fusion
• Reifenstein syndrome- Incomplete virilization characterized by hypogonadism,
severe hypospadias, and gynecomastia
• Gilbert-Dreyfus and Lubs are additional syndromes
24. A 46,XY patient known to
have partial androgen
insensitivity
• Micropenis,
• Urogenital sinus
• Labioscrotal folds
(the left fold contains a
palpable gonad)
25. Partial androgen
insensitivity syndrome at
adolescence
Gynecomastia from
peripheral aromatase
conversion of testosterone to
estrogen
Abundant pubic hair implies
only partial resistance
