APPROACH TO DSD and
AMBIGUOUS GENITALIA
DR. Rashmi Roy 2nd YR JR
DR. Soumik Biswas 2nd YR JR
Department of Paediatrics Medical college Kolkata
Assistant Professor DR. RANA BHATTYACHARJEE
Department of Endocrinology medical college Kolkata
Definition :
Disorders of sex development are group of congenital conditions in which
development of chromosomal, gonadal or anatomical sex is atypical.
• They usually presents at birth
• Involves chromosomes( 46XX, 46 XY, mixed or mosaic), presence of gonads
(testes and ovaries), external genitals
• Often presents as ambiguous genitalia in newborn
Embryogenesis of gonads
Germ cells that arise from coelomic epithelium of hind gut migrate to the urogenital
ridge and give rise to bipotential gonads. Sex cords that is wolffian ducts and mullerian
ducts developed both sides of gonads.
SRY gene on Y chromosome with adjunct Genes like WNT4, RSPO1, FOXL2
to SF1, SOX9, WT1 induce testicular determine ovarian development
development
AMH produced by Sertoli cells In absence of Anti mullerian
cause Mullerian regression, hormone there is persistence of
testosterone produced by Mullerian duct which later
Ledig cells sustains wolffian differentiates into fallopian tube,
ducts and DHT develops male uterus, upper two third of vagina
external genitalia- enlargement
of phallus, scrotum formation,
penile urethra
Steroidogenic pathway
Steroid synthesis takes place in adrenal gland, gonads and placenta. Deficiency of
enzymes at certain step leads to increase precursors which diverted to unaffected
pathways.
Classification of DSD
46 XX DSD 46 XY DSD
• Congenital adrenal hyperplasia • Congenital adrenal hyperplasia
( 21 Hydroxylase, 11b hydroxylase ( 3B HSD, 17 Hydroxylase, POR,
deficiency) StAR deficiency)
• Maternal virilizing tumours • 5a Reductase deficiency
• Maternal ingestion of androgenic drugs • Androgen insensitivity syndrome
• Placental aromatase deficiency • Gonadal dysgenesis
• 46 XX testicular DSD • Ovotesticular DSD
Approach to Ambiguous Genitalia- Gonads are palpable (XY DSD)
USG W/A to see Uterus ( mullerian structure)
PRESENT
ABSENT
Absence of AMH probably due to
Estimate level of Testosterone
gonadal dysgenesis
High or N testosterone low
testosterone
Testosterone DHT ratio defect in androgen
biosynthesis
CAH
INCREASED NORMAL
5 alpha Reductase Androgen Insensitivity syndrome
deficiency
Gonads are non palpable
USG to look for uterus
Uterus absent Uterus present
Do laparoscopy to see intra abdominal gonads
Dealing with XX DSD - CAH
Gonadal dysgenesis or Ovotesticular DSD
17 OHP value
>1000ng/dl Borderline elevated
Normal
21 Hydroxylase
if FSH is high are cystic
Aromatase deficiency
ACTH stimulation
test
17 OH Pregnelenone 11 Deoxycortisol
levels