Dr.Rostampoor

Report
Male sex diffrentiation
• Choromosomal sex
• Gonadal sex
• Sexual phenotype
Gonadal sex
 Urogenital ridge →Primitive gonad 4-5 wk
Testis determination
 Testis determination occurs at about six weeks of
gestation
Testis determination
 The SRY gene initiates the process of testis
determination.
Internal urogenital tract
 Wolffian and mullerian ducts are present in both
sexs
Anti mullerian hormone
 Sertoli cells→:AMH (7wk)
 Regression of mullerian duct
Fetal Leydig cells and androgen production
 Fetal Leydig cells → androgens by 8 to 9 wk
Fetal Leydig cells and androgen production
 Testosterone
 Wolffian duct:
 Epididymides
 Vasa deferentia
 Seminal vesicles
 Ejaculatory ducts
Sexual phenotype
 DHT:androgenization of the external genitalia and
urogenital sinus
Sexual phenotype
 Genital swelling→ Scrotum
 Genital folds → Shaft of the penis
 Genital tubercle →Glans penis
Testis descenting
Testicular descent : at around 12 weeks
• Complete by the middle of the third trimester.
•
Ambiguous or
female external
genitalia
DEFINITION
Incomplete intrauterine
masculinisation with or without
the presence of Mullerian structures
Classification
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
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
‫‪Case 1‬‬
‫‪ ‬دختر ‪ 14‬سال و ‪ 2‬ماهه ای به علت تا خیر بلو غ مراجعه کرده‬
‫است‪.‬وزن بیمار ‪kg 52‬و قد وی ‪ 167‬سانتیمتر می باشد‪.‬‬
‫‪ ‬در معاینه باید به چه نکاتی دقت کرد؟‬
‫‪P/E‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫معاینه از نظر مرحله بلوغ (سینه ها –موهای تناسلی)‬
‫معاینه ژنیتالیا‬
‫معاینه شکم از نظر توده‬
‫عالئم حیاتی با تاکید بر فشار خون‬
case1
 Breast=II, Pubic hair=I
 Genitalia:clitoromegaly,blind vaginal pouch
 BP=110/70
 Other examination:normal
‫‪Lab evaluation‬‬
‫‪ ‬از نظر پاراکلینیک چه ارزیابی هایی درخواست می کنید؟‬
‫‪Lab evaluation1‬‬
‫‪ ‬سونوگرافی شکم و لگن‬
‫‪Lab evaluation1‬‬
‫‪ ‬در سونوگرافی رحم و تخمدان ندارد‪.‬دو توده با اکوی مشابه بیضه در‬
‫اینگوینال‬
‫‪Lab evaluation1‬‬
‫‪ ‬تشخیص احتمالی؟‬
‫‪ ‬بررسی بعدی ؟‬
Lab evaluation1
 LH
 FSH
 Testosterone
 DHT
 Estradiol
 17OHP
 AD
Lab evaluation 1
:‫ آزمایشات‬
17OHP=normal
Testosterone :High
↑Estradiol )for male(
↑↑LH
FSH=Nl
Lab evaluation 1
HCG test 
Lab evaluation 1
 T/DHT=7 ) NL(
Lab evaluation 1
 Karyotype
‫‪Diagnosis‬‬
‫‪ ‬اگر کاریوتیپ بیمار ‪46 XY‬باشد چه تشخیصی مطرح می شود؟‬
Diagnosis
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
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.
Androgen insensitivity syndrome
 These patients are taller (average height 172 cm) and heavier than
normal women
AIS:Lab Data
 ↑ LH and testosterone levels
 ↑Estradiol (for male reference range)
 FSH levels often normal or slightly increased
AIS:Treatment
 Gonadectomy should be performed because of the increased risk
of testicular tumors, especially after puberty.
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
‫‪Case 2‬‬
‫‪ ‬نوزاد ‪ 16‬روزه 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؟‬
‫‪Case 2‬‬
‫‪ ‬چک عالئم حیاتی‬
‫‪ ‬معاینه ژنیتالیا‬
‫‪ ‬چک فشار خون‬
‫‪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
‫‪Case 2‬‬
‫‪ ‬بررسی بعدی؟‬
Case 2
‫ ارسال آزمایشات اولیه‬
 Blood gas
 Na/K
 BS
 Sepsis W/UP
Case 2
 Blood gas:PH=7.15 Hco3=5
 Na=123
 K=7.5
 BS=50
‫‪Case 2‬‬
‫‪ ‬آزمایشات تکمیلی؟‬
Case 2
 17 OHP
 DHEAS
 Testosterone
 Cortisol
Case 2
 ↑17 OHP
 ↑DHEAS
 ↓Testosterone
 ↓Cortisol
‫‪Case 2‬‬
‫‪ ‬تشخیص؟‬
‫‪ ‬درمان ؟‬
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
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
Adrenal crisis Tx
 Serum N/S :10-20 cc/kg
 Serum DW5% with saline 0.9 without kcl
 Stress dose of hydrocortisone(50-100 mg/m2)
 0-3 yr :25 mg /IV
 3-12 yr:50 mg /IV
 > 12 yr:100 mg /IV
 Hydrocortisone :50-100 mg/m2/day q6 hr
Adrenal crisis Tx
 Hypoglycemia:2-4 cc/kg DW10%
 Treat and monitor electrolyte abnormalities
3β-HSD II Deficiency)Tx)
 Glucocorticoid 15-20 mg/m2 /day in 3 doses
 Mineralocorticoids ( salt-losing form):0.05-0.2 mg/day
 Nacl:4 -8 meq/kg/day
 At puberty variable necessity for testesterone replacement
‫‪Case 3‬‬
‫‪ ‬دختر ‪ 15‬ساله ای به علت عدم رشد سینه ها ارجاع شده است‪.‬‬
‫‪ ‬قد ‪ 170‬سانتیمتر و وزن ‪ 58‬کیلو گرم دارد‪.‬‬
‫‪ ‬در معاینه باید به چه نکاتی دقت کرد؟‬
‫‪P/E‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫معاینه از نظر مرحله بلوغ (سینه ها –موهای تناسلی)‬
‫معاینه ژنیتالیا‬
‫معاینه شکم از نظر توده‬
‫عالئم حیاتی با تاکید بر فشار خون‬
Case 3
 Breast =I
 Pubic hair=III
 Genitalia:clitoromegaly(recently enlarge)
 Blind vaginal pouch
 BP=110/80
 Other examination:normal
‫‪Lab evaluation3‬‬
‫‪ ‬از نظر پاراکلینیک چه ارزیابی هایی درخواست می کنید؟‬
‫‪Lab evaluation3‬‬
‫‪ ‬سونوگرافی شکم و لگن‬
‫‪Lab evaluation 3‬‬
‫‪ ‬در سونوگرافی رحم و تخمدان ندارد‪.‬دو توده در ناحیه اینگوینال دیده می‬
‫شود‪.‬‬
‫‪Lab evaluation 3‬‬
‫‪ ‬تشخیص احتمالی؟‬
‫‪ ‬بررسی بعدی ؟‬
Lab evaluation3
 LH
 FSH
 Testosterone
 DHT
 Estradiol
 17OHP
 AD
Lab evaluation 3
:‫ آزمایشات‬
17OHP=normal
Testosterone ,Estradiol=NL(for male)
LH=NL
FSH=Nl
AD=NL
Lab evaluation 3
‫ سن استخوانی‬
Lab evaluation 3
‫ سال‬14=‫ سن استخوانی‬
Lab evaluation 3
HCG test 
Lab evaluation 3
T/DHT=32↑
Lab evaluation 3
 Karyotype
‫‪Diagnosis‬‬
‫‪ ‬اگر کاریوتیپ بیمار ‪46 XY‬باشد چه تشخیصی مطرح می شود؟‬
Diagnosis
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
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
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
Steroid 5-alpha-reductase 2 deficiency
 T and DHT should be measured before and after multiple
injections of hCG.
Steroid 5-alpha-reductase 2 deficiency
 The ratio(T/DHT) generally exceeds 30:1(20:1)
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

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