differential diagnosis of ambiguous genitalia (ag)
DESCRIPTION
Differential Diagnosis of Ambiguous Genitalia (AG). Tian Qin-jie Dept. OB/GYN, PUMCH, CAMS WHO Collaborating Centre for Training and Research in Human Reproductive Health. Determination of newborn’s sex mostly depends on the appearance of external genitalia. - PowerPoint PPT PresentationTRANSCRIPT
Differential Diagnosis of Ambiguous Genitalia (AG)
Tian Qin-jie
Dept. OB/GYN, PUMCH, CAMS
WHO Collaborating Centre for Training and Research in Human Reproductive Health
Determination of
newborn’s sex mostly
depends on
the appearance of
external genitalia
What’s the most common reason?
How do we find the reasons?
Disorders of Sex Development (DSD)
• Definition: DSDs are congenital conditions in which development of chromosomal, gonadal or anatomic sex is atypical– Pediatrics,2006,Nov
• The incidence of DSD is about 1/1,000 newborns– NIH, USA 2000
New classification of disorders of sex development (1996)
Numbers Ratio
Sex chromosome abnormalities: 187 41.6% Turner’s syndrome 166
XO/XY gonadal dysgenesis 10
Super female 7
True hermaphroditism 2
46,XX/46,XY gonadal dysgenesis 1
Klinefelter syndrome 1
Gonadal abnormalities 150 33.3%
XX pure gonadal dysgenesis 119
XY pure gonadal dysgenesis 17
True hermaphroditism 11
Testicular regression 3
Sex hormones abnormalities 113 25.1% Hyperandrogenism 56
Congenital adrenal hyperplasia 55
Excess androgen intake during early pregnancy 1
Hypoandrogenism 14
17-hydroxygenase deficiency 14
Androgen insensitivity syndrome 43
Complete type 15
Partial type 28
Total 450 100.0%
Summary of DSD
• Various types and different etiologies
• Different DSDs might have similar manifestations
• Same DSD might have different manifestation
• Complicated, easily-confused
HOW TO MAKE
A CORRECT
DIAGNOSIS AND
DIFFERENTIAL
DIAGNOSIS?
Key points
• Familiar with each disorders
• Useful clues and procedure
Manifestation of DSD
• AG is one of most common complains– At birth/puberty– 23.3% of DSD, PUMCH, 2001
• Amenorrhea• Underdeveloped breast and/or sexual
hairs• Short status
Basic Knowledge
I. The Differentiation and Development of External Genitalia
• Originates from same structure
• Depends on:– Testis differentiation
• Leydig Cells
– Androgens in genitalia during fetal development• Testosterone 5α -reductase DHT
– Function of androgen receptor (AR)
2. Degree of labium-scrotum fusion related to the timing of androgen
Under influence of high level of androgen – Before gestational 12 weeks
• tend to have more signs of virilism-girl• small penis, hypospadias or partial fusion of scrotum
– After gestational 12 weeks • Girl will only have clitomegaly
Androgen Plays the most important
role in the normal development of external
genitalia
3. Dysfunction of androgen plays the key role in AG
• Androgen excess
• Androgen deficiency
• Failure of gonadal differentiation
Classification of Ambiguous Genitalia- 2001
Cases (N) Percent (%)
Androgen Excess -46,XX
Congenital adrenal hyperplasia (CAH) 55 52.4
Excessive intake of androgen during
early pregnancy
1 1.0
Androgen Deficiency -46,XY
Partial androgen insensitivity
syndrome (PAIS)
28 26.7
Testicular regression 3 2.9
Failure of gonadal differentiation
True hermaphroditism 13 12.4
45,X/46,XY gonadal dysgenesis 5 4.8
Total 105 100.0
Differential Diagnosis• History:
– familial diseases? – drug used during pregnancy?
• PE:– Height, axillary and pubic hairs, breast de
velopment– Size of clitoris, degree of labial fusion, loca
tion of gonads– Pelvic examination: Vagina? Cervix? Uter
us?
Differential Diagnosis
• Sex chromosome
• Serum T, E2, P; LH, FSH, PRL and 17-hydroxyprogesterone
• hCG test, ACTH test, T test, Dexamethasone test
• Laparotomy and laparoscopic examination -nature of gonads
• SRY gene, AR gene analysis
Flow Chart for
differential diagnosis
Ambiguous Genitalia
Breast Development
46,XX 46,XY
CAH PAIS/17OHDTrue Intersex
Ambiguous Genitalia
45,XO 45,XO/46,XY
Turner’s 45,XO/46,XY Gonadal Dysgenesis
Underdeveloped Genitalia
Height<1.50m
Ambiguous Genitalia
Gonad below Inguinal Canal
Testis Ovotestis
Non-CAH True Intersex
Case Study
1. 43-yr-old, social sex female
2. Complains: AG, Amenorrhea, infertility
3. PE: Absence of cervix and uterus
4. Chromosome: 46,XY
5. T:890.78ng/dl
(male:375-950, female:<50)
E:42.11pg/ml
(male:19-52, female:>75)
6. Diagnosis: PAIS
7. DD: Testicular Regression
17OHD
Summary of Contents• One center: Androgen’s key role• Two cardinal points:
– Organogenesis: male and female– Timing of androgen-12 wks
• Three classification of AG Three most common DSDs
Three clues for DD Height, Breast and Location of gonads