Disorders of Sexual Differentiation

Question 1

What is gonadal dysgenesis?

Answer 1

Sexual differentiation is incomplete.
e.g.
A missing SRY in male
Partial/complete deletion of second X chromosome

Question 2

What is sex reversal ?

Answer 2

Phenotype does not match the genotype.

Male genotype with female external

Question 3

What is the definition of Intersex?

Answer 3

Components of both genital tracts are present or ambiguous genitalia

Question 4

What would happen if a individual has XY

Testosterone is made but has no effect ?

Answer 4

Androgen insensitivity syndrome

Question 5

What happens in Androgen insensitivity?

Answer 5

Testes will form and make AMH which causes Mullerian duct regression as there is an SRY gene

Testosterone not working means that there is no Wolffian duct differentiation

They will have no uterus/fallopian tubes

External genitalia will appear female

Primary amenorrhoea(lack of menstrual cycle)

Question 6

What is the outcome of Partial AIS?

Answer 6

The spectrum of phenotypes do vary:

Some have almost normal female external genitalia

Male features are not obvious but at puberty as testosterone levels increase these may become more masculinised.

Question 7

What will happen in the case of a XY male who is unable to make /respond to AMH in utero?

Answer 7

Persistent Mullerian duct syndrome

Question 8

What mutations can cause Persistent Mullerian duct syndrome?

Answer 8

PMDS type 1 is due to a mutation of the gene for AMH on chromosome 19

PMDS type 2 from mutation of gene for AMH receptor (AMH-RII) chromosome 12

Question 9

What will be the outcome of PMDS?

Answer 9

Testes will form as SRY is present but fail to make AMG /or AMH receptor may be absent.
Result= Mullerian ducts remain
Differentiation of Wolffian ducts and masculinised external genitalia

Question 10

What genitalia do individuals with PMDS have ?

Answer 10

The result is a intra-abdominal mullerian structure and testes in a position instead of ovaries
(Inguinal sac)

Some have one testis in a hernial sac /scrotum together with Mullerian structure
(Hernia uteri inguinalis)

10% have testes both located in hernial sac (transverse testicular ectopia) along with uterine tubes and uterine structures

May lead to malignancy

Question 11

What treatment options are available for PMDS

Answer 11

Surgery to retrieve testes and position in scrotum
(Testosterone replacement at puberty if testes cannot be retrieved)

Removal of uterus dissection of Mullerian tissue away from Vas deferens /epididymis

Laparoscopic hysterectomy to prevent neoplastic tissue formation

Question 12

What will happen if an XY individual has testosterone but not DHT ?

Answer 12

5 alpha reductase deficiency.

due to a problem with the 5 alpha reductase gene

Question 13

What will happen in 5 alpha reductase deficiency

Answer 13

SRY means there will be the regression of Mullerian ducts due to the release of AMH.

Testosterone will lead to development of the Wolffian ducts and seminal vesicles and vas deferens.

Lack of DHT means no male external genitalia.

Question 14

What symptoms can be detected with 5 alpha reductase deficiency ?

Answer 14

Have ambiguous genitalia, such as labioscortal folds, clitoridean penis

Levels of testosterone needs to be assessed during puberty , adrenarche - may cause virilisation (

Question 15

What is Virilisation?

Answer 15

Women developing male hair growth patterns

Question 16

What is 45XO?

Answer 16

Turners syndrome

Question 17

What will Turners syndrome cause ?

Answer 17

They have ovarian dysgenesis 
Streak ovaries 
(Both X chromosomes are required for normal ovarian development)

Uterus /tubes are present

May be fertile , may have mosaicism

Issues with hormone support of bones and uterus

Question 18

What causes Mosaicism in females ?

Answer 18

This is as a result of X inactivation or no X chromosome.

Depends on when that X chromosome may have been lost which means that some cells will have it whilst others do not .

Question 19

What will happen when a XX female is exposed to high levels of androgens in utero ?

Answer 19

Congenital adrenal hyperplasia

Question 20

Outline the hypothalamic pituitary adrenal axis

Answer 20

Hypothalamus 
           I
CRH  (corticotrophin-releasing hormone ) 
           I
Pituitary 
           I
ACTH (Adrenocorticotropic hormone)
           I
Adrenal glands (Make cortisol +negative feedback)

Question 21

What does corticotropin releasing hormone do ?

Answer 21

Stimulate pituitary to secrete ACTH

Question 22

What does Adrenocorticotropic hormone do ?

Answer 22

Stimulate rapid uptake of cholesterol into the adrenal cortex
Upregulates cholesterol side-chain cleavage enzyme
Increases glucocorticoid secretion

Question 23

What happens to the HPA axis in congenital adrenal hyperplasia?

Answer 23

There is no production of cortisol which means there is no negative feedback loop which leads to a increase of androgens.

Granulosa cells do not yet express aromatase which causes a build up.

Question 24

How would a CAH patient be treated ?

Answer 24

Glucocorticoids

No aldosterone is made which causes salt wasting