لهال م
سب
حیمالر
لرحمنا
46 XY DSD
Noushin RostampourAssistant Professor Of Pediatric EndocrinologyShahrekord University Of Medical Science
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:EpididymidesVasa deferentiaSeminal vesicles Ejaculatory ducts
Sexual phenotype
DHT:androgenization of the external genitalia and urogenital sinus
Sexual phenotype
Genital swelling→ ScrotumGenital folds → Shaft of the penisGenital tubercle →Glans penis
• Testicular descent : at around 12 weeks• Complete by the middle of the third
trimester.
Testis descenting
DEFINITION
46 XY DSD
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 deficiency17α-hydroxylase/17,20-lyase deficiencyPOR deficiency 17-βHSD 3 deficiency 5α-reductase 2 deficiency3-DEFECTS IN ANDROGEN ACTIONAIS
4-otherPersistence of Müllerian ducts syndrome
Case 1
و 14دختر مراجعه 2سال غ بلو خیر تا علت به ای ماهه . بیمار وزن است وی kg 52کرده قد می 167و سانتیمتر
باشد. کرد؟ دقت نکاتی چه به باید معاینه در
P/E
) تناسلی ) – موهای ها سینه بلوغ مرحله نظر از معاینه ژنیتالیا معاینه توده نظر از شکم معاینه خون فشار بر تاکید با حیاتی عالئم
case1
Breast=II, Pubic hair=IGenitalia:clitoromegaly,blind vaginal pouch BP=110/70Other examination:normal
Lab evaluation
کنید؟ می درخواست هایی ارزیابی چه پاراکلینیک نظر از
Lab evaluation1
لگن و شکم سونوگرافی
Lab evaluation1
. با توده دو ندارد تخمدان و رحم سونوگرافی دراینگوینال در بیضه مشابه اکوی
Lab evaluation1
احتمالی؟ تشخیص ؟ بعدی بررسی
Lab evaluation1
LHFSHTestosteroneDHTEstradiol 17OHPAD
Lab evaluation 1
:آزمایشات17OHP=normal
Testosterone :High
↑Estradiol (for male)
↑↑LH
FSH=Nl
Lab evaluation 1
HCG test
Lab evaluation 1
T/DHT= ) 7NL(
Lab evaluation 1
Karyotype
Diagnosis
بیمار کاریوتیپ می XY 46اگر مطرح تشخیصی چه باشدشود؟
Diagnosis
Androgen insensitivity syndrome
Androgen insensitivity syndrome
Loss of function mutations of the gene that encodes the androgen-receptor
X-linked recessiveCAIS ,PAISFemale external genitaliaAmbiguous Hypospadias Vagina is either absent or short and blind-endingTestes may be located in the abdomen, the inguinal canals, or the
labia majora1-2% 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 massesWomen with primary amenorrheaAdolescent girls who become virilized and develop clitoromegalyAdult men with undervirilization or with infertility associated
with azoospermia or severe oligospermia
Case 2
شده 16نوزاد ارجاع لتارژی و حالی بی با ای روزهکاهش . نوزادی رفلکسهای و بوده دهیدره معاینه در است
. دارد؟ اهمیت نکاتی چه معاینه در است یافته
Case 2
حیاتی عالئم چک ژنیتالیا معاینه خون فشار چک
Case 2
- میکروپنیسو شاخه دو اسکروتوم ژنیتالیا معاینه دردارد هیپوسپدیاز
باشد می اسکروتوم در ها بیضه است پائین خون فشار و بوده کارد کی تا
Case 2
بعدی؟ بررسی
Case 2
اولیه آزمایشات ارسالBlood gasNa/KBSSepsis W/UP
Case 2
Blood gas:PH=7.15 Hco3=5Na=123K=7.5BS=50
Case 2
تکمیلی؟ آزمایشات
Case 2
17 OHPDHEASTestosteroneCortisol
Case 2
↑17 OHP↑DHEAS↓Testosterone↓Cortisol
Case 2
تشخیص؟ ؟ درمان
3-beta hydroxy stroid dehydogenase II deficiency
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 ARAmbiguous 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 kclStress dose of hydrocortisone(50-100 mg/m2)0-3 yr :25 mg /IV3-12 yr:50 mg /IV> 12 yr:100 mg /IVHydrocortisone :50-100 mg/m2/day q6 hr
Adrenal crisis Tx
Hypoglycemia:2-4 cc/kg DW10%Treat and monitor electrolyte abnormalities
Tx))3β-HSD II Deficiency
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
ارجاع 15دختر ها سینه رشد عدم علت به ای ساله. است شده
وزن 170قد و .58سانتیمتر دارد گرم کیلو
کرد؟ دقت نکاتی چه به باید معاینه در
P/E
) تناسلی ) – موهای ها سینه بلوغ مرحله نظر از معاینه ژنیتالیا معاینه توده نظر از شکم معاینه خون فشار بر تاکید با حیاتی عالئم
Case 3
Breast =I Pubic hair=III Genitalia:clitoromegaly(recently enlarge)Blind vaginal pouchBP=110/80Other examination:normal
Lab evaluation3
کنید؟ می درخواست هایی ارزیابی چه پاراکلینیک نظر از
Lab evaluation3
لگن و شکم سونوگرافی
Lab evaluation 3
. در توده دو ندارد تخمدان و رحم سونوگرافی در . شود می دیده اینگوینال ناحیه
Lab evaluation 3
احتمالی؟ تشخیص ؟ بعدی بررسی
Lab evaluation3
LHFSHTestosteroneDHTEstradiol 17OHPAD
Lab evaluation 3
:آزمایشات17OHP=normal
Testosterone ,Estradiol=NL(for male)
LH=NL
FSH=Nl
AD=NL
Lab evaluation 3
استخوانی سن
Lab evaluation 3
= استخوانی سال 14سن
Lab evaluation 3
HCG test
Lab evaluation 3
T/DHT=32↑
Lab evaluation 3
Karyotype
Diagnosis
بیمار کاریوتیپ شود؟ XY 46اگر می مطرح تشخیصی چه باشد
Diagnosis
Steroid 5-alpha-reductase 2 deficiency
Autosomal recessive Inadequate conversion of T→DHTAmbiguous external genitalia MicropenisHypospediasBlind vaginal pouch Normal internal male genitaliaProstate 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 deficiencyout 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