Pre-pubertal and congenital gynaecological disorders

Question 1

What are common intersex conditions also known as and what are the two ways they can present?
(EMERGENCY)

Answer 1

DSD - disorders of sexual differentiation

1. congenital abnormality (CAH)
2. later in life - androgen insensitivity syndrome - presents with amenorrhoea

Question 2

How is DSD classified (disorders of sexual differentiation)

Answer 2

based upon underlying genotype

Question 3

What is the most common DSD with 46XX genotype?

Answer 3

Congenital adrenal hyperplasia (CAH)

Question 4

What can 46XY genotype cause? (2)

Answer 4

1. AIS

2. 5-alpha reductase deficiency

Question 5

What type of genetic condition is CAH?

Answer 5

autosommal recessive

Question 6

What enzyme is most commonly deficient in CAH?

Answer 6

21-hydroxylase deficiency

Question 7

What happens in CAH?

Answer 7

reduction in cortisol and aldosterone production.

ACTH levels rise - precursor steroid - prengenolone is shunted into the androgen synthesis pathway

Question 8

What are the symptoms of CAH? (3)

Answer 8

1. Salt wasting (adisonion) crisis in infants
2. Virilisation of female genitalia -> ambigious
3. precocious puberty in males

Question 9

What investigations do you do for CAH?

Answer 9

imagine =

pelvic/renal/bladder US

virilsation with a female uterus makes CAH likely

Question 10

What is the treatment for CAH? (2)

Answer 10

Gender assignment

Cortisol and aldosterone replacement therapy

Question 11

What type of condition is androgen insensitivity syndrome?

Answer 11

X-linked recessive condition

Question 12

What happens in androgen insensitivity syndrome?

Answer 12

due to end organ resistance to testosterone -> causes genotypically male children (46XY) to have a female phenotype.

Question 13

What is the new term for testicular feminisation syndrome?

Answer 13

Complete androgen insensitivity syndrome

Question 14

What are the symptoms for complete AIS?

Answer 14

appear female at birth.

present with amenorrhoea and lack of body hair.

will have undescended testes and an absent uterus.

however breast development can occur as a result of testosterone coversion to oestrodiol

Question 15

What are the symptoms of partial AIS?

Answer 15

varying degree of genital development.

cliteromegaly - ambigious genitalia

Question 16

How do you diagnose androgen insensiticity syndrome? (2)

Answer 16

1. Buccal smear

2. Chromosomal analysis to reveal 46XY genotype

Question 17

What is the management for androgen insensivity syndrome? (3)

Answer 17

1. counselling - raise child as female
2. Bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
3. Oestrogen therapy

Question 18

What type of condition is 5-alpha reductase deficiency?

Answer 18

autosomal recessive condition

Question 19

What happens in the 5-alpha reductase deficiency?

Answer 19

inability of males to convert testosterone into DHT (responsible for external genetalia differentiation)

Question 20

What is the result of 5-alpha reductase deficiency? (3)

Answer 20

internal male structures are formed but external are not.

may appear female or have ambigious genitalia

can undergo virilisatoin at puberty due to high levels of circulating testosterone

Question 21

What is the management of 5-alpha reductase deficiency and if they are raised male or female?

Answer 21

gender assignemnt.

if raised male = DHT + testosterone replacement therapy

If raised female = oestrogen replacement therapy