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AMBIGUOUS GENITALIA
Presented by : Dr. Abhay Pota
www.dnbpediatrics.com

TABLE OF CONTENTS
• Introduction
• Revised nomenclature
• Normal sexual development
• Evaluation of a new born with suspected dsd
• 46 xx dsd
• 46 xy dsd
• Gonadal differentiation disorders
• Issues of sex assignment and issues prior to it
- Surgery
- Medical treatment
- psychological & genetic counceling and support
• Key pointers
• In essence

Pointers
DEFECT POINTERS
PIGMENTATION CAH, SFI defect
GENITAL ASYMMETRY MGD, OT, DSD
HYPERTENSION 11(X) or 17 (x) hydroxylase
defect
HEMIHYPESTROPHY WT 1mutation
RENAL FAILURE Denish drash syndrome

Sperleng
• High intrauterine concentrations of
testesterone may influence brain
development.
• Affecting later behaviour and the formation of
gender identity.

Nursery evaluation of a newborn with
suspected DSD
HISTORY PHYSICAL EXAMINATION
Family h/o External genitals
Neonatal death Gonadal size, position and
descent
maternal drug exposure Bimanual rectal examination
maternal virilization Associated anamolies
Placental insufficiency
Prenatal findings

Male pseudo : 46 XY
DSD
Female Pseudo : 46 XX
DSD
GENOTYPE XY XX
EXTERNAL
GENITALIA
are female are virilized
As there is no AMH, Mullersion
duct develops into uterus, tubes
and ovaries. But due to presence
of excess androgens external
genitalia are virilized

True hermaphroditism – ovotesticular
DSD
• Both ovarian and testicular tissues present
in same or opposite gonads.

Evaluation of a new born with
suspected DSD
• [1] DSD work up required in :
i. Infants with genital ambiguity
ii. Girls with inguinal masses ( ? AIS)
iii. Boys with cryptorchidism (? AHS)
iv. Penoscrotal hypospadias (? undervision nth
samjatu )
v. Adollescent girls with amenorrhoea (? AIS)

Introduction
Ambigo
us
genitali
a
Psudoh
ermaph
roditis
m
DSD
Intersex
• Revised nomenclature &
classification i.e.
considerate of molecular
genetics non derogatory
• Despite many advances
specific cause of DSD can
not always be found
especially in XY DSD.

[c] Diagnostic tests
• (1) Lab tests
- first line
- second line
- chromosomal analysis
• (2) Pelvic USG
• (3) Genitogram (VCUG)

Time course of sexual differentiation
• (1) FT
• Only period during which labioscrotal fusion
can occur
PLACENTAL HCG
LTR RECEPTOR ON TESTES
TESTESTERONE SYNTHESIS

• [2] ST & TT
• In females, clitoromegaly and darkening and
virgation of labioscrotal folds.
FETAL PITUATARY
LH
TESTESTERONE
PENILE SIZE, SCROTAL MATURATION
& TESTICULAR DESCENT

APPROACH TO CRYPTORCHIDISM
PALPABLE GONADS
Hcg test
Retractile or
ectopic testis
No treatment Hcg trial
Assess scrotal development
Undescended
testis
Descended Not Descended
FU Orchidopexy
Undescended
testis
Anorchia
Surgery
Laparoscopy

Revised nomenclature
INTERSEX DSD
[1] MALE PSEUDOHERMAPHRODITE
UNDERVIRILATION OF AN XY MALE 46, XX DSD
UNDERMASCULIZATION OF AN XY MALE
[2] FEMALE PSEUDOHERMAPHRODITE
OVERVIRILATION OF AN XX FEMALE 46, XY DSD
MACULIZATION OF AN XX FEMALE
[3] TRUE HERMAPHRODITE OVOTESTICULAR DSD
[4] XX SEX REVERSAL 46 XX TESTICULAR DSD
[5] XY SEX REVERSAL 46, XY COMPLETE GONADAL
DYSGENESISwww.dnbpediatrics.com

So, in essence
• 1- Early consultation with pediatric
endocrinologist
• 2- Not disclosing sex of child hastily when in
doubt
• 3- Thorough knowledge of endocrine system,
genital development and genetic studies
• 4- Team approach
• 5-

Estrogen
Ovary
BIPOTENTIAL GONADS
Wolffian development
AMH Testesterone
External genitalia
UROGENITAL RIDGE
Mullersion
development
GERM CELLS + SOMATIC CELLS
Testis
DHT

GONADAL SEX
PALPABLE GONADS
GENETIC SEX

21 SW + FPH + N female newborn later precocious P.
11 HT + FPH + No hypoglycemia + N male NB later
precocious P.
3 SW + FPH + MPH
17 HT + MPH + No hypoglycemia + N Female NB later
precocious P
Star SW + MPH + N female NB later precocious

Issues of sex assignment and issues
prior to it
• change in beliefs and practise
• 2 dielemmas
- in 46 XX CAH
- in 46 XY no penile tissues
• Counseling of parents
• Multidisciplinary approach
• Guarded approach in immediate revealing of sex
• Thorough investigation
• Until a sex assignment is made withhold, giving gender
specific names or references
• Circumcision c/I

Ovotesticular DSD
• Both ovarian + testicular tissues present,
either in same or opposite gonads.
• Cause unknown
i. Highly viviinadequate testicular tissue –
uterus- reared on male
ii. Virilization minimal + unadequate testicular
tissue + uterus reared on female

• Diagnosis by histology and gonadal biopsy
• Surgically remove the inconsistent tissue

AIS – most common form of male DSD
• Reijenstein syndrome
• Gilhert dreytuos syndrome
• Rey syndrome
• Hcg does not raise
testesteronre PALS
• Test : DHT ratio normal
AIS
Partial Complete

• Evaluation :
1. Monthly 25-50 mg IM testesterone for 3
months
- No increase in size of penis by 2 cm PALS
2. Genetic studies for mutation in receptor
3. Sex assignment
- PALS – male
- CALS - female

46 XX DSD
• [1] CAH
- most common cause of XX DSD as well as overall
- females with 21 and 11 hydroxylase defects are
most highly virilized
- salt loosers have more virilization as compared
to non salt loosers.
- male : female = 1:1
- incidence – 1 : 16,000.

• [2] Aromatase deficiency
- both mother and infant are virilized due to
inability to convert androgens to estrogens
• [3] maternal hyperandrogenic conditions
- virilizing tumours, exposure to androgenic drugs
during pregnancy
• [4] Glucocorticoid receptor mutation
- antley Bixler syndrome

• [4] undermined causes –
- smith – cemli apitz syndrome
- Kallman syndrome
- growth hormone deficiency
- kleinfelter
- prader willi
- Downs
- Noonan
- Fanconi’s
- fetal hydantoin syndromes

• [5] cryptorchidism
- 3 : 1000 more in premature
- USG / MRI
- Hcg stimulation test, AMH, FSH, LH,
testesterone levels measured
- Orchidopexy at 1 year
- If not possible remove them _____

• [2] defects in testicular hormones
i. CAH
ii. Leydig cell aplasia – AR
- female phenotype
- testes + epididymis + VAS – uterus FT
- secondary sexual characters
- LH , testosterone

Defects in androgen action
i. 5 α , reductase deficiency type 2 gene of ch.2 defect
Testo 5α DHT
R
wolffian external genitalia
structures
- Normal testosterone
- DHT
- Testo : DHT ratio
- Secondary sexual characters and spermatogenesis normal

46 XY DSD
• Complex
• Early referral to ped. Endocrinologist
• 50 % cases then also remain undiagnosed

• [1] defects in testicular differentiation
i. Denys rash syndrome – WR1 mutation
- DSD + B/L wilm’s + nephropathy
- diffuse mesangial sclerosis
nephrotic syndrome
ESRD by 8 yrs
ii. WAGR syndrome – WR1 mutation
-wilms + aniridiaa + GU anamolies + retardation
- WAGRO

• iii. Campomelic syndrome – SOX9 mutation
- bowing of tibia and femur, small thoracic
cavity, DSD, malformations of other organs
• Iv. Swyer syndrome – SRY gene mutation
- XY pure gonadal dysgenesis
- vagina + uterus + FT – breast – menses

• V. XY gonadal agenesis syndrome
- vanishing testes syndrome/ embryonic
testicular regression syndrome
- hypoplastic labia + perineal urethral opening
+ clitoris – uterus gonadal tissue – vagina –
sexual development

Regression of testes
• Before 8 weeks – swyer syndrome
• 8-14 weeks – rudimentary testes syndrome
• > 14 weeks - anoechia

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