Dis of Sex Diff

Question 1

Define gonadal dysgenesis

Answer 1

→Sexual differentiation is incomplete.

→Usually missing SRY in male, or partial or complete deletion of second X in female

→Also used as a general description of abnormal development of the gonads.

Question 2

What is sex reversal?

Answer 2

→Phenotype does not match genotype, ie may be male genotypically but externally look like a female

Question 3

What is intersex?

Answer 3

→Have some components of both tracts or have ambiguous genitalia.

Question 4

What is androgen insensitivity syndrome?

Answer 4

→Testosterone is made but has no effect

Question 5

What happens AIS?

Answer 5

→Testes form and make AMH so Mullerian ducts regress.

→No differentiation of Wolffian ducts

→No external male genitalia- no descended testes

→no uterus or fallopian tubes

→External genitalia appear female - abbreviated blind vaginal pouch.

Question 6

What is a clue for AIS?

Answer 6

→lack of body hair

Question 7

What does ultrasound and karyotyping reveal in AIS?

Answer 7

→male levels of androgen

Question 8

What is partial AIS?

Answer 8

→Minor genital deviations go unnoticed or may be surgically repaired.

→At puberty development of male secondary characteristics may not be very pronounced. In some cases pubertal gynecomastia (androgen/estrogen ratio) or ambiguous genitalia surgically corrected. Androgen therapy in some cases.

Question 9

What happens if XY male is unable to make or respond to AMH in utero?

Answer 9

Persistent Mullerian duct syndrome

→limited to XY offspring

Question 10

What is PMDS type I?

Answer 10

→from mutations of the gene for AMH on chromosome 19

Question 11

What is PMDS type II?

Answer 11

→mutations of the gene for the AMH receptor (AMH-RII) on chromosome 12

Question 12

What happens in PMDS?

Answer 12

→Testes form and either fail to make AMH or AMH receptor absent.

→Mullerian ducts remain.

→Differentiation of Wolffian ducts and masculinised external genitalia

Question 13

What are the treatments for PMDS?

Answer 13

→Surgery (orchiopexy) to retrieve the testes and position them in the scrotum. If testes cannot be retrieved, testosterone replacement at puberty is an option

→Removal of uterus dissection of Müllerian tissue away from the vas deferens/epididymis.

→Laparoscopic hysterectomy may prevent the occurrences of neoplastic tissue formation

Question 14

What are the common presentation for PMDS?

Answer 14

→60–70% of cases have intra-abdominal Mullerian structures and testes in a position simulating that of the ovaries

→20–30% have one testis in a hernial sac or scrotum together with Mullerian structures.

→10% have both testes located in the same hernial sac (transverse testicular ectopia) along with the uterine tubes and/or uterine structures.

→All have increased risk of malignant transformation.

Question 15

What happens if an XY individual produces testosterone but not DHT?

Answer 15

→5-α-Reductase Deficiency

Question 16

What happens in 5-α-Reductase Deficiency?

Answer 16

→Testes form and make AMH so Mullerian ducts regress

→Wolffian ducts develop

→No external male genitalia

Question 17

Describe 5a-reductase defieciency

Answer 17

→Testes form, AMH acts, testosterone acts. Internal structures form. External male structures do not fully develop

→May appear mainly female or may have ambiguous genitalia such as labioscrotal folds or clitoridean penis

→Both testosterone and dihydrotestosterone (DHT) are capable of masculinising the brain in non-human primates so some brain

Question 18

Describe Turner’s Syndrome

Answer 18

→XO have failure of ovarian function. ‘Streak’ ovaries = ovarian dysgenesis

→ Uterus and tubes are present, may be small or other defects in growth and development

Question 19

What does Turner’s syndrome illustrate about ovarian development?

Answer 19

→we need two Xs for ovarian development

Question 20

What may those with Turner’s syndrome suffer from?

Answer 20

→hormone deficiency and uterus

Question 21

What happens if XX female is exposed to high levels of androgens in utero?

Answer 21

→Congenital adrenal hyperplasia

Question 22

What happens in CAH?

Answer 22

→No SRY so no testes and no AMH.

→Mullerian ducts remain.

→Masculinised external genitalia, but androgen levels not usually high enough to rescue Wolffian ducts.

Question 23

What does ACTH stimulate?

Answer 23

→rapid uptake of cholesterol into the adrenal cortex

→Upregulates cholesterol side-chain cleavage enzyme (P450scc).

→Increases glucocorticoid secretion

Question 24

Describe CAH presentation

Answer 24

→May have developed Wolffian structures and ambiguous masculinised external genitalia or hirsutism

Question 25

What may those with CAH also experience?

Answer 25

→salt wasting due to lack of aldosterone

Question 26

How can CAH be treated?

Answer 26

→glucocorticoids to correct feedback