1. 1.Will be able to understand how the sex of each individual is determined .
2. To know which abnormalities in sex determining factors that will result in intersex.
3. Will be able to understand how these abnormalities are presented clinically at birth, during childhood and adolescence
4. Will be able to reach to the diagnosis of different cases of intersex and how to manage them

2. INTERSEX The effect of sex chromosome on the undifferentiated gonads
The proper function of the differentiated gonads
The response of the end organs to testicular activity

4. The effect of sex chromosome
They determine the final functional morphology of the undiff. Gonads by the following:
1.Presence of Y chr. In association with one or more X chr. the gonads develop into testis
2.If more than X chr. present with Y chr. ,the gonads differentiation to testis is normal during I.U life but testicular develop. during puberty is impaired
3.If tow or more X chr. Are present without Y chr. the undiff. Gonads will develop into ovary.
4.If more than tow X chr.present the subsequent ovarian develope. During puberty is impaired.

5. The presence of Y chr. Will promot testicular diff
The presence of Y chr. Will promot testicular diff . through TDF ,the gene of which present on the short arm of chr. TDF regulate H-Y Ag whose gene present on Y chr. or outosome. H-Y Ag is a plasma mem. Protein & is widely distributed in cells.

10. The effect of testicular function on sexual develop.
During IU life the presence of functioning testis will result in male phenotype Absence or presence of non functioning testis will always lead to a female phenotype whether ovaries are present or not. So male develop. Is the result of presence of testis & female develop. Is the result of absence of testis This function of testis during IU life is through secretion of 2 substances which are : 1. testosterone from Leidg cells 2.MIF from Sertoli cells . It is aglycoprotein & it has a unilateral action & Mullerian structures are sensitive to it only during the first 8 weeks of gestation

11. The response of end organs
Testosteron secreted from testis will initiate develop. of male ext. & int. genital structures The Wolfian structurs are able of utilizing test. directly while ext. genitelia utilize test. After conversion to dihydrotest. By 5α reductase enz. For effective utilization both hormones , it is necessary for test. to be bound to receptors in the cytoplasm of cells . So ineffective binding will lead to abnormal sexual develop.

12. Abnormal sexual developement
1.Abnormality in sex chr. which interfer with testicular develop the only common one is 45 XO/46 XY mosaism leading to one form of gonadal dysgenesis. 2.Testis may be unable of producing testosterone either because of anatomical or enzymatic testicular failure. 3.The end organ may be unable of utilizing testos. because of 5α reductase deficiency or failure of testost. binding(androgen insensitivity). 4.The production of MIF may be deficient leading to the growth of Mullerian system in a male.

13. 5. In a genetic female (46 X X) musculinization of ext
5.In a genetic female (46 X X) musculinization of ext. genitalia may result in excessive androgen production as in congenital adrenal hyperplesia or from androgen from other sources. 6.Rarely in agenetic female, the gene capable of production of H-Y Ag may be found on an autosome leading to 46 XX male 7.True hermaphrodite i.e the presence of testicular & ovarian tissue in the same individual

16. Clinical presentation during infancy &childhood
The childe with ambigouos genitalia may present in a number of ways: 1.Musclinized female 2.Under musclinized male 3.True hertmaphrodite3

17. When the condition discovered at neonatal period the first diagnosis to be confirmed is that of CAH because it is a correctable condition and the baby may die if it is of salt loosing type So when a childe or neonate presented with ambiguous genitalia ,we should look for the presence of testis up to the inguinal area and the first concern is to exclude a musclinized female ( CAH or excessive androgen). If these causes had been excluded, then the diagnosisis either an undermusclinized male or true hermaphrodite

18. C A H
It is the most common cause of female intersex ,and it is an autosomal recessive disorder which is due to enzymetic deffect. The commonest is 21 hydroxylase defficiency 90% &less commonly is 11β hydroxylase defficiency

22. linical features 1. clitoral hypertrophy. 2
linical features 1. clitoral hypertrophy. 2. Excessive fusion of labia minora which obscure the vagina & urethra forming an artificial urogenital sinus which has an opening on the perineum near the base of clitoris. 3.Thickining of labia majora which may resemble scrotum of testis 4.The uterus ,fallopian tubes & vagina are present which open in the urogenital sinus. 5. In some infant ,a dangerous salt loosing syndrom may arise due to associated aldosteron defficiency and the infant may die from wasting and vomiting within few weeks of life if the diagnosis is delayed

24. So when a neonate or infant preset with ambiguous genitalia , the initial exam. don to identify the presence or absence of testis . If they are absent then the diag. of CAH is raised & the following investg. should be done: 1. Karyotyping on a sample of cord blood. 2. Measurement of 17 α hydroxyprogesteron in blood increase . If this I not available then measurement of pregnantriol in urine is done. 3.Measurement ofandrogen level in urine by assaying urinary 17 oxosteroid. 4.Electrolyt level in serum , if salt loosing syndrome present then Na &Cl are low and K is elevated. 5. Pelvic U/S to confirm the presence of uterus& vagina

25. Management Should be immediate:
1.Cortizol or corticosteron to suppress ACTH.
2.In salt loosing type ,correction of elect. defect.
3.Surgical correction of ext. genitalia in the form of:
A. Reduction in the size of clitoris
this is better done during neonatal period & is either by amputation or by reduction clitoroplasty.
B. Division of the fussed labial folds in order to expose the vagina and urethra.
this op. don at any age at the same time of op & it may need to be repeated later during puberty

26. Those patient can achieve normal menses & fertility but usually the menarche is delayed 2 years specially in those with inappropriate hormonal control Some patients may be presented with menstrual irregularity as oligomenorrhea , amenorrhea or even infertility specially in salt loosing type

27. 1. Causes of interesex at birth & infancy.
2. Clinical presentation of intersex after infancy & causes

28. Other causes of musclinized female
1. Androgen secreting tumor during pregnancy e.g androblastoma 2. The use of progestationl drugs that have androgenic effect 3.Idiopathic The presentation of neonate or child is the same for CAH & no other metabolic defect The management initially is to exclude CAH and if this is excluded , the treatment should be in the form of surgical correction as in CAH

29. If musclinization of a genetic female from excessive androgen had been excluded then distinction most be made bet. An undermusclinized male & tre hermaphrodite. The distinction can be made only by laparotomy & gonadal biopsy . Laparoscopic biopsy is not an adequate procedure for establishing the nature of a gonad in intersex. Gonadal biopsy is not don to choose the sex of rearing ,which is don according to the suitability of the ext. genitalia for sexual life. But still it is important to know the nature of the gonads in order to remove the inappropriate tissue for the chosen sex .

30. Male intersex (XY female)
A. Fault in androgen production
1.Anatomical testicular failure:
there may be abnormality in testicular development & differentiation
The clinical presentation depend on testicular diffretiation but usualy there is very milde musclinization of ext. genitalia. The uterus,tubes & vagina are present (absence of MIF)
Management:
*surgery for reconstruction of ext. genitalia as in CAH

31. Removal of streaks of gonads bec. Of risk of maleg
*Removal of streaks of gonads bec. Of risk of maleg. *At time of puberty replacement with estrogen &progesteron for develop.of secondary sex character & menstruation 2. Enzymatic testicular failure There is a defect in the biosynthesis of testosterone and musclinization will depend on the degree of defect the uterus ,tubes & vagina are absent. The management will depend on the degree of musclination but the female role is usually chosen (surgery with removal of gonads).

32. B. End organ insensitivity
1. 5α reductase enz. deficiency
There is poor musclinization of ext. genitalia & it is an autosomal recessive disorder
Conformation of the dig. Is by giving HCG to stimulate the gonads & measuring testosteron level before & after treatment .
The management also depend on the degree of musclinization
If the condition is undiagnosed & the childe is grown up as a female , at time of puberty & increase in testosteron production there will be verilization & the patient may wish to change the sex to amale so management should be before puberty

33. 2. Androgen insensitivity
If the defect is complete ,then the patient is normal (normal female ext. genitalia) but at time of puberty present as primary amenorrhea
If the defect is partial then the presentation would be at birth with ambiguous genitalia.
The management is as previous with surgery (reconstruction of ext.genitalia &removal of testis) with hormonal replacement at puberty).

34. True hermaphrodite
* This condition is common in South Africa .The presentation vary with varying degree of ambiguity but usually uterus, tubes and vagina are present. * The karyotype in most cases is that of 46 XX, the next common is 46 XX/ 46 XY then 46 XY. * The distribution of the gonads is that the most frequent is the presence of ovitestis in one side &an ovary on the other one * The other common is the presence of an ovary on one side & a testis on the other . * Diagnoses is by gonadal biopsy * The sex of rearing would be determined according to the functional capacity of the ext.genitalia after which the inapropperiate gonads are removed. * If it is not possible to identify the ovarian tissue from testicular one then both should be removed & replacemant therapy at puberty is given.

35. When the patient presented after infancy
Usually if the condition is not apparent at birth ,the patient would be presented some years later at time of puberty & the complain would be 1.Some heterosexual features become evident 2.Pre-existing minor heterosexual features become more profound. 3.Sometimes intersex is present since childhood but was ignored & not investigated. The investigation for such patient would be the same as in infancy & childhood & only differ minor aspect e.g. in case of CAH the possibility of salt loosing syndrome is excluded Another aspect is that in the management we should consider the type of sex that the patient been adjusted to and no attempt to change it e,g, patient with androgen insensitivity.

36. Androgen insensitivity
It is most likely to be evident for the first time at or after puberty but may be discovered earlier during childhood (complete insensitivity). The presentation at puberty is that of primary amenorrhea in a female with absence of pubic & axillary ,normal ext. genitalia but short blind vagina . The uterus is absent &the testis are found within the abdomen, in the inguinal canal or within labia. The karyotype is 46 XY. Hormonal assay show *normal testosteron level of male. *LH is increased due to insensitivity of hypoth. & pituitary to testosteron. *FSH level may be slightly raised.

38. This abnormality is due to the lack of androgen receptors The diag
This abnormality is due to the lack of androgen receptors The diag. may be made early during childhood when testis are found within a hernial sac or the presence of the syndrome in an older sister in the family & karyotype of 46 XY. The management will depend on the age of the patient If it is at or after puberty then the management is by removal of the testis (risk of malignancy) & give hormone therapy (acyclical estrogen because there is no uterus) . If the condition discovered during childhood & there is no obvious heterosexual feature , then removal of testis may be delayed after puberty to get some

39. feminizing features , but if there is heterosexual features then the gonads should be removed at childhood followed by hormone therapy at puberty & onward Surgery may be required for very short vagina in the form of vaginoplasty or the use of vaginal dilators

40. C A H
Patient with CAH who had been grown as female are unlikely to have sufficient musclinization of ext. genitalia , so surgery is not required Sometimes in cases that had been misdiagnosed since birth or undiagnosed due to the presence of extreme musclinization & the childe had been grown as male, so it is wise to let the patient live as a male but cortezol should be given ,then the patient would menstruate(due to decrease in androgen) so total hysterectomy with oopherectomy is done .

41. 5 α reductase defficiency
If the deficiency is complete then the diag. is not made till time of puberty , when the patient who is grown as a female would have a male type puberty with verilization. So the management would depend on the functional capacity of ext. genitalia but usually the female role is chosen

42. T rue hermaphrodite
The presentation at puberty would depend on the function of the gonads .e.g. menstruation may occur at puberty in a hermaphrodite who had been thought to be a male .So in such cases hysterectomy with removal of ovarian tissue should be done with mastectomy if there is breast developement

43. * 46 XXmale dos not present as intersex but may have hypospadias.
* 46 XY male with isolated MIF deficiency also dos not present as intersex but Mullarian structures may be found in the abdomen of a male during laparotomy.