By Dr. Nadia AL.Assady F.I.B.O.G C.A.B.O.G

1. Intersex By Dr. Nadia AL.Assady F.I.B.O.G C.A.B.O.G

2. Introduction

3. there has been a recent change in the terminology used to refer to these conditions. older terms are confusing to both the clinician & patients & can be hurtful which include : a-46 XY DSD b-46 XX DSD c- ovotesticular DSD

4. There are 3 factors that determine sexual development • 1-the effect of sex chromosomes on the differentiation of the gonads. • 2-the proper functioning of the differentiated testis • 3-the response of the end organ to this testicular function

5. The testis carry out their intrauterine function by producing 2 substances: • a. Testosterone. • b. mullerian inhibitory factors. • The testosterone give rise to the development of wolffian duct • MIF it is glycoprotein produced by sertoli cells which inhibit the development of mullerian duct

6. Its have unilateral action &each testis appear to produce the MIF which result in regression mullerian structures on its own sides . • The sensitivity of mullerian structures to MIF is present only during the first 8 wk of gestation.

7. Clinical presentation: • The child with ambiguous genitalia may present in a numbers of ways: • 1 .a masculinized female due to CAH or androgen stimulation from another sources. • 2. an under masculinized male . • 3.true hermaphrodite.

8. Congenital adrenal hyperplasia • Its an autosomal recessive disorders ,resulting in enzyme deficiency related to the biosynthesis of cortisol & aldosterone . the commonest enzyme defect is 21-hydroxylase ,its account for(90%) of cases this result in increase in progesterone& 17 – hydroxyprogesterone which than converted to androsterodione& then to testosterone.

9. CLF: • The incidence rate between(1/5000-1/15000) those females born with enlargement of clitoris &excessive fusion of labia majora resemble the scrotum which obscure the vagina & urethra . • The uterus ,fallopian tubes & vagina are always present .in some infants dangerous salt losing syndrome may arise because of associated aldesterone deficiency & the child may die from wasting & vomiting within few wks of life if the case not diagnose.

10. Management • Counseling the parents &reassure them that the child is healthy but there is developmental error of genitalia & if examination fail to identify palpable gonads so the child most likely female.

11. Investigation: • 1. karyotyping performed on cord blood. • 2.measurement 17 hydroxy progesterone in blood which increased. • 3.electrolytes levels to exclude salt losing syndrome. (here Na & CL may reduce &K increase). • 4.pelvic U/S to see the uterus & vagina. • Treatment • Medical by cortisone • Surgical by cliteroplasty & division of fused labia.

12. XY FEMALE • This condition result from either: • A .abnormal androgen production. This is due to • 1-anatomical testicular failure: • Failure of normal testis development may be due to the chromosomal mosaicim & here the condition called pure gonadaldysgensis

13. CLF/ most patient have mild masculinization or none at all, the uterus, tubes & vagina are present • Management • 1. reconstruction of external genitalia • 2.removal of streak gonads because the potential risk of malignancy • 3.HRT are giving around the age of puberty to induce secondary sexual characters & menstruation

14. 2-enzymatic testicular failure: • There is biosynthetic steps defect in the formation of testosterone • CLF/ there is variable degree of ambiguous genitalia the uterus, tubes & vagina are absent because MIF production is normal. • Management • 1-decision of sex of rearing usually female • 2-surgical reconstruction

15. B . insensitivity to androgen production. this is due • 1.5 –alpha reductase deficiency : • Normal masculinization of the external genitalia require the conversion of testosterone to dihydrotestosterone by 5-alpha reductase.

16. CLF/In this case the male infant have poor masculinization of external genitalia but the uterus ,tubes & vagina are absent • .most child are place in femle role. At puberty the testis produce high amount of testosterone & there is greater virilization to extent the patient wish to change the gender from female to male

17. Management 1-decision of sex of rearing 2-surgical reconstruction • 2.androgen insensitivity syndrome • this is due to complete absence of the gene for androgen receptor & called complete AIS. • If there is mutation or defect of gene so there is partial receptor binding & called partial AIS.

18. CLF/ • most patient present for first time after puberty with primary amenorrhea despite normal breast development • on examination there is scanty or absent axillary &pubic hair ,normal vulva but short blind vagina no palpable cervix

20. management • 1.karyotyping reveal 46 XY male pattern • 2.endocrine testing: • a-testosterone level within normal male range. • b-estrogen level are within the range where normal male & female value overlap • 3.laproscopy reveal absent uterus& testis found in the abdomen ,inguinal canal & labia.

21. Treatment • a. counseling the patient that they are entirely female despite their karyotypes. • b. discussion with the patient the need for removal of their gonads because the risk of malignancy. • c.HRT with estrogen only because have no uterus. • d. if the vagina not functional so graduated dilatation using frank procedure. • True hermaphrodite

25. Thank you