1- Sexual Disorders

Question 1

what is gonadal dysgenesis?

Answer 1

disorders where sexual differentiation is incomplete, causes abnormal development of the gonads

Question 2

what are the four example disorders for gonadal dysgenesis?

Answer 2

adrenal insufficiency syndrome = testosterone is produced but to no effect

5-alpha-reductase deficiency = testosterone is produced, DHT isn’t due to lack of 5-alpha-reductase

turner syndrome = female individual has XO chromosomes

congenital adrenal hyperplasia = a group of genetic disorders affecting the adrenal glands’ ability to produce sex hormones, related to a 21-hydroxylae deficiency

Question 3

what is androgen insensitivity syndrome?

Answer 3

when testosterone is made in an XY person but to no effect

Question 4

effects on internal and external genitalia development with androgen insensitivity syndrome

Answer 4

testes form and make AMH = Mullerian ducts regress

testosterone produced but to no effect = Wolffian ducts regress, no DHT produced, undescended testes

no internal male or female genitalia, external female genitalia

Question 5

characteristics of androgen insensitivity syndrome

Answer 5

primary amenorrhoea
undescended testes - detected by an ultrasound
ambiguous genitalia - varying degrees of penile development, large clitoris

Question 6

treatment options for androgen insensitivity syndrome

Answer 6

• surgery for undescended testes
• waiting after puberty is an option = testosterone levels are higher, can lead to further masculinisation of genitalia

Question 7

what is 5-alpha-reductase deficiency?

Answer 7

absence of 5-alpha-reducrase = testosterone is produced, DHT isn’t

Question 8

effects on internal and external genitalia development with 5-alpha-reductase deficiency

Answer 8

testes form and make AMH = Mullerian ducts regress

Leydig cells produce testosterone = Wolffian ducts develop

no DHT = male external genitalia can’t develop, undescended testes

internal male genitalia, female-looking external genitalia

Question 9

characteristics of 5-alpha-reductase deficiency

Answer 9

• ambiguous/ female-looking external genitalia
• external genitalia may appear more masculine during puberty following adrenarche = higher testosterone levels have some effect
• virilisation and more male external genitalia following puberty

Question 10

mode of inheritance for 5-alpha-reductase deficiency

Answer 10

autosomal recessive

Question 11

what is turner syndrome?

Answer 11

a female with XO chromosome

Question 12

effects on internal and external genitalia development with turner syndrome

Answer 12

no AMH = Mullerian ducts present

no testosterone = Wolffian ducts regress

‘streak ovaries’ - don’t form correctly during foetal development

internal and external female genitalia

Question 13

relating to X inactivation, how does turner syndrome affect development?

Answer 13

X inactivation is the random inactivation of one X chromosome in each somatic cell of a female, independent from each cell

ends of the repressed X chromosome - pseudo-autosomal regions - are still active, and the second chromosome still affects development

both X chromosomes are needed for proper development. Turner syndrome (XO) lacks one X chromosome

Question 14

characteristics of turner syndrome

Answer 14

failure of ovarian function, streak ovaries

uterus and uterine tubes are small, defected growth and development

Question 15

how does presentation vary with turner syndrome?

Answer 15

presentation varies depending on when the X chromosome was lost

if it was during the one-cell stage, all cells will have one X chromosome

if it was later on in development, there may be a mosaic pattern of XX and XO between cells

Question 16

what is congenital adrenal hyperplasia?

Answer 16

a group of genetic disorders affecting the adrenal glands’ ability to produce sex hormones, related to a 21-hydroxylaase deficiency

Question 17

how does 21-hydroxylase deficiency lead to gonadal dysgenesis?

Answer 17

21-hydroxylase is important for cortisol synthesis. cortisol is synthesised from cholesterol as a steroid hormone

ACTH and CRH increase from lack of negative feedback, but still no cortisol production

excess cholesterol is taken up by the adrenal gland, increases progesterone production in the developing female foetus.

progesterone is converted to testosterone - disrupts female gonadal development

Question 18

effects on internal and external genitalia development with congenital adrenal hyperplasia

Answer 18

no AMH = Mullerian ducts remain

testosterone present = Wolffian ducts remain, masculinised external genitalia for female foetus

androgen levels usually aren’t high enough to fully rescue Wolffian ducts

some internal male structures along with Mullerian structures, masculinised external genitalia

Question 19

characteristics of congenital adrenal hyperplasia

Answer 19

• level of deficiency for 21-hydroxylase affects development = ambiguous genitalia, assigned the wrong gender at birth (male instead of female)
• salt-wasting = 21-hydroxylase deficiency means adrenal glands don’t make enough aldosterone. too much sodium lost in urine.