1. 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

2. Determination of newborn’s sex mostly depends on the appearance of external genitalia

3. What’s the most common reason? How do we find the reasons?

4. 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

5. 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
Gonadal abnormalities
150
33.3%
XX pure gonadal dysgenesis
119
XY pure gonadal dysgenesis 17 11
Testicular regression 3
Sex hormones abnormalities
113
25.1％
Hyperandrogenism 56
Congenital adrenal hyperplasia 55
Excess androgen intake during early pregnancy
Hypoandrogenism 14
17-hydroxygenase deficiency
Androgen insensitivity syndrome 43
Complete type 15
Partial type 28
Total
450
100.0％

6. Summary of DSD Various types and different etiologies
Different DSDs might have similar manifestations
Same DSD might have different manifestation
Complicated, easily-confused

7. HOW TO MAKE A CORRECT DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS?

8. Key points
Familiar with each disorders
Useful clues and procedure

9. Manifestation of DSD AG is one of most common complains Amenorrhea
At birth/puberty
23.3% of DSD, PUMCH, 2001
Amenorrhea
Underdeveloped breast and/or sexual hairs
Short status

10. Basic Knowledge

11. 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 α -reductase DHT
Function of androgen receptor (AR)

12. 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

13. Androgen Plays the most important role in the normal development of external genitalia

14. 3. Dysfunction of androgen plays the key role in AG
Androgen excess
Androgen deficiency
Failure of gonadal differentiation

15. 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

16. Differential Diagnosis
History:
familial diseases?
drug used during pregnancy?
PE:
Height, axillary and pubic hairs, breast development
Size of clitoris, degree of labial fusion, location of gonads
Pelvic examination: Vagina? Cervix? Uterus?

17. 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

18. Flow Chart for differential diagnosis

19. Ambiguous Genitalia Breast Development 46,XX 46,XY CAH True Intersex
PAIS/17OHD

20. Underdeveloped Genitalia
Height<1.50m
Underdeveloped Genitalia
Ambiguous Genitalia
45,XO
45,XO/46,XY
Turner’s
45,XO/46,XY
Gonadal Dysgenesis

21. Ambiguous Genitalia Gonad below Inguinal Canal Testis Ovotestis
Non-CAH
True Intersex

22. Case Study

23. 43-yr-old, social sex female
Complains: AG, Amenorrhea, infertility
PE: Absence of cervix and uterus
Chromosome: 46,XY
T:890.78ng/dl
(male: , female:<50)
E:42.11pg/ml
(male:19-52, female:>75)
6. Diagnosis: PAIS
7. DD: Testicular Regression
17OHD

24. 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