VIVEKENANDA PATEDA ,SpA

DIVISI ENDOKRIN IKA

RSUP Prof Kandou/FK UNSRAT

1 : 4500 1 : 5500
50 % : Hiperplasia adrenal kongenital
1:10000 Mixed Gonadal Dysgenesis (MGD)

Fase determinasi
-faktor kromosom
-faktor gonad

Fase diferensiasi
-faktor hormonal genitalia int dan ext

Gangguan fase ini

DSD (gangguan

perkembangan sistim reproduksi atipikal)

The development of male internal genitalia in human embryo.

The 6-wk-end embryo is equipped with both male and female
genital ducts derived from mesonephrons

MALE

Y chromosome

Primordial
gonad

SRY gene
Testis

Anti-Mullerian hormone, AMH

(Mullerian duct)

Dihydrotestosterone
(DHT)

Male external
genitalia

Testosterone

+
Wolffian duct

FEMALE

Primordial gonad

Ovarium

Anti-Mullerian
Hormone
(AMH) -

chromosome X (SRY gene -)

Testosterone (-)

Mullerian duct

Dihydrotestoste
rone
Uterus, tuba, vagina
(DHT)

Wolffian duct

Female external genitalia

female

male

MALE
Genital tubercle penis
Urethral folds urethra,phallus
Urogenital swellings scrotum
Penile growth and testicular
descent
occur in the third trimester
- Sinus Urogenitalia Prostat

FEMALE
Genital tubercle clitoris
Genital swellings
labia majora
Urethral folds labia
minora
Sinus UG Vagina

BEFORE

X X X

Male
Female
Pseudohermaph Pseudohermaph
rodite
rodite

True
Hermaphrodite

Gonadal
Dysgenesis

DSD
46,XY DSD

46,XX DSD

Sex Chromosome DSD

Sebelumnya

Sekarang

Intersex

DSD

Male
Pseudohermaphroditism

46, XY DSD

Female
Pseudohermaphroditism

46,XX DSD

True Hermaphrodite

Ovotesticular DSD

Sex Reversal (pembalikan)

XX male
XY female

46, XX testicular DSD

46, XY complete gonadal
dysgenesis
(Hughes et al, 2006; Lee et al, 2006)

Etiologi DSD sangat luas

Nomenklatur DSD membagi etilogi DSD atas ;
46,XY DSD, 46,XX DSD, DSD kromosom
sex,DSD ovotestikuler, 46,XX DSD testikuler
Klasifikasi dasar DSD dibagi atas :
Disgenesis

Gonad
46,XY udervirilisation
46,XX virilisation

Sex chromosome DSD

46,XY DSD

46,XX DSD

45,X (Turner Syndrome and

variant)

Disorders of gonadal (testicular)

development:
Complete gonadal dysgenesis (Swyer
syndrome; partial gonadal dysgenesis;
gonadal regression; ovotesticular DSD

Disorders of ovarian development:

ovotesticular DSD; testicular DSD (eg.
SRY, duplicate SOX9; gonadal
dysgenesis

47,XXY (Klinefelter syndrome

and variant

Disorders in androgen synthesis or action:

androgen biosynthesis defect (eg 17-HSD
defic, 5ARD2 defic, StAR mutation; defect
in androgen action (CAIS, PAIS); LH rec
defect; disorders of anti Mullefian
hormone angi Mullerian hormone receptor

Androgen excess: fetal (21OH defic;

11OH defic); fetoplacental (aromatase
defic, POR. And maternal (luteoma,
exogenous)

45,X/46,XY (MGD, ovotesticular

DSD)
46,XX/46,XY (chimeric,
ovotesticular DSD

Other (closcalextrophy. Vaginal atresia,

MURCS

Male undervirilisation

Female with virilisation

EXCESS FETAL
ANDROGENS
Congenital adrenal
hyperplasia
21-hydrxylase deficiency
11-hydroxylase
deficiency
3-hydroxysteroid
dehydrogenase deficiency
Aromatase Defisiency

EXCESS MATERNAL
ANDROGENS
Maternal androgen
secreting tumours
(ovary, adrenal)
Maternal ingestion of
androgenic drugs

The commonest cause of genital

ambiguity at birth
21-OHase deficiency is most
common form
Autosomal reccessive
Salt wasting form may be lethal in
neonates
SERUM 17OH-progesterone
(21-hydroxylase defisiensi)
SERUM deoxycorticosterone, 11deoxycotisol (11- hydroxylase def)

Genitalia externa
;Klitoromegali,hiper
pigmentasi
XX :
Ovarium,genitalia
int (+) perempuan
Testosteron
maskulinisasi

46-XY/SRY
Testis AMH
Testosterone
5--rductase
DHT
Female or Ambiguous
external Genitalia
(mikropenis,korda,hipo
spadia berat,skrotum
bifidum)

Male Internal
Genitalia

46-XY/SRY
TESTIS AMH
Testosterone
5--reductase
DHT
Absent androgen
receptors
Female/ambi
guous External
Genitalia

Male
Internal
Genitalia

Female, age 3 weeks

Palpable

gonad (testes) on the left

scrotum (volume <2ml)
Phallus 1cm
Chromosome
Karyotype: 45,XO
FISH: 45,XO/46,XY/47,XYY
(mosaic)
Genitogram: No Mullerian structures
detected
Mullerian detected at gonadectomy.
Right testes not found.

Neonatus fenotip perempuan

tanpa ambigus
Disfungsi gene SRY
Umumnya dengan ; delayed
puberty, primary
amenorrhoe
Peningkatan FSH/LH
androgen dan
klitoromegali
resiko dari tumor germ
cell (30% at 30 years)
Sebagian besar diasuh sbg
perempuan
Terapi : gonadectomy
,reduksi klitoris,vaginoplasti
and hormone replacement

46, XY
No SRY OR its receptors
Streak gonad bilateral
- NO AMH (Uterus +)
hipoplasia
- NO SEX STEROIDS

Genitalia ext :
Female,TB
normal,delay
puber,amenore primer

Female Internal
Genitalia (hipoplasia
uterus,gonad pita
bilateral)

Mutations in the R-spondin1

(RSPO1) gene
1 in 20000 males. All Infertile
Complete/near complete male
phenotype
Microtestes but 10% have
hypospadias, no uterus
80% SRY positive - like
Klinefelters but smaller and
normal proportions
Probably translocation of Y
chromosome material to X
chromosome or mutation of a X
chromosome gene
Tx/ androgen substitution

 Karyotype :
46,XX most common (57%);
XY(13%) and XX/XY(30%)
Gonad
- ovary one side and testis on
the other or
- bilateral ovotestis
Internal genitalia :
Both mullerian and wolffian
derivates
Phenotype ambigus/variable
Gonadal biopsy is required for
confirming diagnosis

Clinical features:
Male
Usually/often tall
Long arms and legs
Breast development
Underdeveloped/fibrosis testes
impaired testoteron production
Frequency: about 1 in 1000 male
births

ANAMNESIS
Riwayat kelainan serupa dalam keluarga (AIS,
CAH,5 alfa reduktase def)
Riwayat kematian neonatal dini (CAH)
Virilisasi saat puber
Infertilitas dalam keluarga
Riwayat terpapar obat-obat selama hamil

Pemeriksaan Fisik
Keadaan umum : gagal tumbuh,retardasi
mental
mikrosefali,hipertensi
Wajah dismorfik + ambigus (sydrom??)
Stigmata short stature (tinggi seseorang),low
post harline,web neck, limfedema (Turner
Synd)

Gonad + /Phallus : < 2 cm bayi baru lahir mikropenis

Mikropenis +/- (umuran < - 2,5 SD)
Klitoromegali (klitoris > 1 cm)
Hiperpigmentasi ?/Orifisium uretra (normal terpisah dari introitus
vagina)
Rasio anogenital (> 0,5 Virilisasi)

1.Hanya hipertrofi klitoris, genitalia ext lain

fenotip perempuan
2.Hipertrofi klitoris,jarak sinus UG,vagina
dan uretra berdekatan
3. Hipertrofi klitoris,sinus UG dangkal
4.Phallus dengan meatus urogenital kecil
5.Fenotip genitalia laki-laki normal

Analisis kromosom
Pencitraan :
USG pelvis dan Genitogram
Pemeriksaan hormonal : testosteron,LH,FSH,17 OHP,
rasio testosteron/dehidrotestosteron (DHT)dengan
uji HCG,5 alfa reduktase
Molekuler genetik
Endoskopi/laparaskopi
Histopatologi dan imunokimiawi

History
Perinatal, family,
medicine
Physical examination
BP, gonad, dysmorphic
Chromosome
analysis
Karyotype +/ - FISH
Karyotype XX

Gonad

Karyotype XY
(+)

(-)

Rule out CAH (17- OH progesterone)

11 deoxicortisol
DHEA
ACTH
PRA
Aldosteron
Serum/ urine electrolytes
ACTH stimulation test

Other tests
DNA analysis
(specific)

Imaging of internal
genitalia: Ultrasonografi
+/ - genitogram
If needed:
Pelvic MRI/ CT scan
Laparascopy

Karyotype XO or
XXY or mosaicism

FISH/ DNA for SRY

gene
hCG stimulation
test
SRY (-) or
SRY mutation (+)

no
Other tests:
Testosteron/ DHT
Androstenedion, A/T ratio
AMH
ACTH stimulation test
GnRh stimulation test
DNA analysis (specific)

Turner syndrome/ variant

Kleinefelter syndrome
Mixed Gonadal Dysgenesis

yes

Swyer syndrome/
Complete Gonadal
Dysgenesis/
SRY (-) Testicular/
ovotesticular DSD
Allen L. Obstet Gynecol Clin N Am 20

Tujuannya :
Menjamin semaksimal mungkin fertilitas
Menjamin semaksimal mungkin fungsi seksual
Menjamin kesesuian hasil akhir fenotip dan
psikososial dengan jenis kelamin yang
ditentukan

Penentuan Gender
Hendaknya sesegera mungkin setelah diagnosis
ditegakkan
Terapi hormonal ( HCG, testosteron,estrogen)
Pembedahan
-Kliotoroplasti
-Koreksi chordae
-Gonadektomi pada disgenesis testis
-Vaginal dilatation

Thank you