1. بسم الله الرحمن الرحیم

2. 46 XY DSD Noushin Rostampour
Assistant Professor Of Pediatric Endocrinology
Shahrekord University Of Medical Science

4. Male sex diffrentiation
Choromosomal sex
Gonadal sex
Sexual phenotype

5. Gonadal sex
Urogenital ridge →Primitive gonad 4-5 wk

6. Testis determination
Testis determination occurs at about six weeks of gestation

7. Testis determination
The SRY gene initiates the process of testis determination.

8. Internal urogenital tract
Wolffian and mullerian ducts are present in both sexs

9. Anti mullerian hormone
Sertoli cells→:AMH (7wk)
Regression of mullerian duct

10. Fetal Leydig cells and androgen production
Fetal Leydig cells → androgens by 8 to 9 wk

11. Fetal Leydig cells and androgen production
Testosterone
Wolffian duct:
Epididymides
Vasa deferentia
Seminal vesicles
Ejaculatory ducts

12. Sexual phenotype
DHT:androgenization of the external genitalia and urogenital sinus

13. Sexual phenotype Genital swelling→ Scrotum
Genital folds → Shaft of the penis
Genital tubercle →Glans penis

14. Testis descenting Complete by the middle of the third trimester.
Testicular descent : at around 12 weeks
Complete by the middle of the third trimester.

15. Ambiguous or female external genitalia
DEFINITION
46 XY DSD
Ambiguous or female external genitalia

16. DEFINITION Incomplete intrauterine masculinisation with or without
the presence of Mullerian structures

17. Classification

18. Classification 2-Testosterone synthesis defects
1-ABNORMALITIES OF GONADAL DEVELOPMENT
Complete or partial gonadal dysgenesis
Testis regression syndrome
Ovotesticular 46,XY DSD
2-Testosterone synthesis defects
LH receptor mutations
Smith-Lemli-Opitz syndrome
Steroidogenic acute regulatory protein mutations
Cholesterol side chain cleavage (CYP11A1) defects

19. Classification 3-β-HSD 2 deficiency
17α-hydroxylase/17,20-lyase deficiency
POR deficiency
17-βHSD 3 deficiency
5α-reductase 2 deficiency
3-DEFECTS IN ANDROGEN ACTION
AIS
4-other
Persistence of Müllerian ducts syndrome

20. Case 1
دختر 14 سال و 2 ماهه ای به علت تا خیر بلو غ مراجعه کرده است.وزن بیمارkg 52 و قد وی 167 سانتیمتر می باشد.
در معاینه باید به چه نکاتی دقت کرد؟

21. P/E معاینه از نظر مرحله بلوغ (سینه ها –موهای تناسلی) معاینه ژنیتالیا
معاینه شکم از نظر توده
علائم حیاتی با تاکید بر فشار خون

22. case1 Breast=II, Pubic hair=I
Genitalia:clitoromegaly,blind vaginal pouch
BP=110/70
Other examination:normal

23. Lab evaluation
از نظر پاراکلینیک چه ارزیابی هایی درخواست می کنید؟

24. Lab evaluation1
سونوگرافی شکم و لگن

25. Lab evaluation1
در سونوگرافی رحم و تخمدان ندارد.دو توده با اکوی مشابه بیضه در اینگوینال

26. Lab evaluation1
تشخیص احتمالی؟
بررسی بعدی ؟

27. Lab evaluation1 LH
FSH
Testosterone
DHT
Estradiol
17OHP AD

28. Lab evaluation 1 آزمایشات: 17OHP=normal Testosterone :High
↑Estradiol (for male)
↑↑LH
FSH=Nl

29. Lab evaluation 1
HCG test

30. Lab evaluation 1
T/DHT= ) 7NL(

31. Lab evaluation 1
Karyotype

32. Diagnosis
اگر کاریوتیپ بیمار 46 XY باشد چه تشخیصی مطرح می شود؟

33. Androgen insensitivity syndrome
Diagnosis
Androgen insensitivity syndrome

34. Androgen insensitivity syndrome
Loss of function mutations of the gene that encodes the androgen-receptor
X-linked recessive
CAIS ,PAIS
Female external genitalia
Ambiguous
Hypospadias
Vagina is either absent or short and blind-ending
Testes may be located in the abdomen, the inguinal canals, or the labia majora
1-2% girls with inguinal hernia

35. Androgen insensitivity syndrome
The urogenital tract :absence or near absence of müllerian structures
Breast development is that of a normal woman, but has not had her menarche
Axillary and pubic hair are markedly decreased or absent.

36. Androgen insensitivity syndrome
These patients are taller (average height 172 cm) and heavier than normal women

37. AIS:Lab Data ↑ LH and testosterone levels
↑Estradiol (for male reference range)
FSH levels often normal or slightly increased

38. AIS:Treatment
Gonadectomy should be performed because of the increased risk of testicular tumors, especially after puberty.

39. Possibility of AIS Girls with inguinal hernias or labial masses
Women with primary amenorrhea
Adolescent girls who become virilized and develop clitoromegaly
Adult men with undervirilization or with infertility associated with azoospermia or severe oligospermia

40. Case 2
نوزاد 16 روزه ای با بی حالی و لتارژی ارجاع شده است .در معاینه دهیدره بوده و رفلکس های نوزادی کاهش یافته است.در معاینه چه نکاتی اهمیت دارد؟

41. Case 2
چک علائم حیاتی
معاینه ژنیتالیا
چک فشار خون

42. Case 2 در معاینه ژنیتالیا اسکروتوم دو شاخه-میکروپنیس و هیپوسپدیاز دارد
بیضه ها در اسکروتوم می باشد
تا کی کارد بوده و فشار خون پائین است

43. Case 2
بررسی بعدی؟

44. Case 2
ارسال آزمایشات اولیه
Blood gas
Na/K BS
Sepsis W/UP

45. Case 2
Blood gas:PH= Hco3=5
Na=123
K=7.5
BS=50

46. Case 2
آزمایشات تکمیلی؟

47. Case 2
17 OHP
DHEAS
Testosterone
Cortisol

48. Case 2
↑17 OHP
↑DHEAS
↓Testosterone
↓Cortisol

49. Case 2
تشخیص؟
درمان ؟

50. 3-beta hydroxy stroid dehydogenase II deficiency

51. 3β-Hydroxysteroid Dehydrogenase type II Deficiency
3β-HSD is essential for the biosynthesis of mineralocorticoids, glucocorticoids and sex steroids
It affects both adrenal and gonadal AR
Ambiguous external genitalia, (micropenis,perineal hypospadias,bifid scrotum and a blind vaginal pouch)
With or without salt loss

53. 3β-HSD II Deficiency(Lab)
↑17-OHPreg either basally or after ACTH stimulation
17-OHP and AD may also be elevated
Most of the patients were raised as males

54. Adrenal crisis Tx Serum N/S :10-20 cc/kg
Serum DW5% with saline 0.9 without kcl
Stress dose of hydrocortisone( mg/m2)
0-3 yr :25 mg /IV
3-12 yr:50 mg /IV
> 12 yr:100 mg /IV
Hydrocortisone : mg/m2/day q6 hr

55. Adrenal crisis Tx Hypoglycemia:2-4 cc/kg DW10%
Treat and monitor electrolyte abnormalities

56. Tx))3β-HSD II Deficiency
Glucocorticoid mg/m2 /day in 3 doses
Mineralocorticoids ( salt-losing form): mg/day
Nacl:4 -8 meq/kg/day
At puberty variable necessity for testesterone replacement

57. Case 3 دختر 15 ساله ای به علت عدم رشد سینه ها ارجاع شده است.
دختر 15 ساله ای به علت عدم رشد سینه ها ارجاع شده است.
قد 170 سانتیمتر و وزن 58 کیلو گرم دارد.
در معاینه باید به چه نکاتی دقت کرد؟

58. P/E معاینه از نظر مرحله بلوغ (سینه ها –موهای تناسلی) معاینه ژنیتالیا
معاینه شکم از نظر توده
علائم حیاتی با تاکید بر فشار خون

59. Case 3 Breast =I Pubic hair=III
Genitalia:clitoromegaly(recently enlarge)
Blind vaginal pouch
BP=110/80
Other examination:normal

60. Lab evaluation3
از نظر پاراکلینیک چه ارزیابی هایی درخواست می کنید؟

61. Lab evaluation3
سونوگرافی شکم و لگن

62. Lab evaluation 3
در سونوگرافی رحم و تخمدان ندارد.دو توده در ناحیه اینگوینال دیده می شود.

63. Lab evaluation 3
تشخیص احتمالی؟
بررسی بعدی ؟

64. Lab evaluation3 LH
FSH
Testosterone
DHT
Estradiol
17OHP AD

65. Lab evaluation 3 آزمایشات: 17OHP=normal
Testosterone ,Estradiol=NL(for male)
LH=NL
FSH=Nl
AD=NL

66. Lab evaluation 3
سن استخوانی

67. Lab evaluation 3
سن استخوانی=14 سال

68. Lab evaluation 3
HCG test

69. Lab evaluation 3
T/DHT=32↑

70. Lab evaluation 3
Karyotype

71. Diagnosis
اگر کاریوتیپ بیمار 46 XY باشد چه تشخیصی مطرح می شود؟

72. 5-alpha reductase deficiency
Diagnosis
5-alpha reductase deficiency

73. Steroid 5-alpha-reductase 2 deficiency
Autosomal recessive
Inadequate conversion of T→DHT
Ambiguous external genitalia
Micropenis
Hypospedias
Blind vaginal pouch
Normal internal male genitalia
Prostate hypoplasia
No müllerian structures are present.
The testes are usually located in the inguinal region

75. Steroid 5-alpha-reductase 2 deficiency
Virilization and deep voice appear at puberty, along with penile enlargement, and muscle mass development
These patients present scarce facial and body hair and absence of temporal male baldness, acne and prostate enlargement

76. 5-alpha-reductase 2 deficiency :Lab Data
Concentrations of serum testosterone and estrogens are similar to those in normal men.
LH is normal or slightly elevated
Measurement of basal serum concentrations of T and DHT is not sufficient for diagnosis before the expected age of puberty

77. Steroid 5-alpha-reductase 2 deficiency
T and DHT should be measured before and after multiple injections of hCG.

78. Steroid 5-alpha-reductase 2 deficiency
The ratio(T/DHT) generally exceeds 30:1(20:1)

79. Steroid 5-alpha-reductase 2 deficiency out come
≥50 percent of 46,XY patients with this disorder undergo change in gender role from female to male after the time of expected puberty

80. Thanks for your attention