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