Dr.Rostampoor
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Transcript Dr.Rostampoor
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