CM: Disorders Sex Differentiation

Question 1

What is the role of AMH in sexual differentiation?

Answer 1

produced by sertoli cells - leads to regression of Mullerian structures (uterus, tubes, upper vagina)

Question 2

What is the role of testosterone in sexual differentiation?

Answer 2

produced by Leydig cells - stimulates dev of testicles and Wolffian structures (epididymis, vas deferens, seminal vesicles)

Question 3

What is the role of DHT in sexual differentiation?

Answer 3

promotes dev of external male genitalia

Question 4

What are critical concepts related to in utero development?

Answer 4

testosterone and AMH depend on high local concentrations - defects can be unilateral
DHT bilateral except true hermaphrodites
concept of critical dev windows

Question 5

What is the role of testosterone at puberty?

Answer 5

activation of hypothalamic-gonadal axis - sperm production, increased size and muscle mass, deepening of voice
dev of facial and chest hair (w DHT)

Question 6

What does DHEA-S do during puberty?

Answer 6

dev of sexual hair pattern (axillary and pubic)

does not depend on functioning gonads

Question 7

What is the role of estrogen at puberty?

Answer 7

breast dev, increase in uterine size and endometrial growth, allows for menstruation in response to ovulation

Question 8

What is gonadal dysgenesis?

Answer 8

ovary or testes which is functionally and often anatomically abnormal or absent = streak gonads
can be seen w normal or abnormal karyotypes
*Y containing gonadal tissue must be removed

Question 9

What are the features of Klinefelter’s syndrome?

Answer 9

47 XXY
SRY –> testes and normal in utero to male
phenotype evident during puberty - small firm testes w poor testosterone and sperm production (but still adequate for IVF/ICSI)
gynecomastia, tall and euchonoid (longer limbs), less muscle, more body fat, decreased facial and body hair, broad hips
*gonads do not need to be removed

Question 10

What are the features of Turner’s syndrome?

Answer 10

45X
short, web neck, shield chest, hearing loss, renal and cardiac abnormalities
streak gonads - uterus remains small, no breast dev
int and ext female genitalia (no AMH, DHT)
adrenarche normal but no axillary and pubic hair
mosaics MAY have cyclic menses and fertility

Question 11

What are the features of mixed gonadal dysgenesis?

Answer 11

45X/46XY
asymmetric gonadal dev - single cryptorchid testes and streak gonad (must be removed)
presentation ranges - poor AMH means most have some mullerian dev

Question 12

What is gonadal dysgenesis w a normal karyotype?

Answer 12

specific gene defects

mutations in SF-1 that regulates SRY –> gonadal and adrenal agenesis

Question 13

What are 46XX DSD?

Answer 13

female genotype w male genotype - CAH or elevated maternal androgens

Question 14

What is the presentation of 46XX DSD?

Answer 14

virilization of external genitalia, range from clitoromegaly and labial fusion to normal phenotypic male
normal female internal genitalia - no AMH
breast dev and menses at puberty

Question 15

What can cause elevated maternal androgens?

Answer 15

drug intake, androgen producing tumors (luteoma), placental aromatase def

Question 16

What is 46XY DSD?

Answer 16

genetic male, phenotypic female
bilateral testes
defects in androgen synthesis in testes or androgen action in target cell
still AMH –> no mullerian structures

Question 17

What can cause impaired androgen responsiveness?

Answer 17

mutations in receptor or 5alpha-reductase def

testes dev and produce AMH and testosterone

Question 18

What is androgen insensitivity syndrome?

Answer 18

AMH so no mullerian, but no wolffian - can’t respond to testosterone
normal female external genitalia - can’t respond to DHT
breasts at puberty but no pubiv hair
remove testes at puberty!
basically - make testosterone but cannot respond

Question 19

What is 5alpha-reductase def?

Answer 19

prevents conversion of testosterone to DHT
generally incomplete - low levels of DHT
normal internal male

Question 20

What do mutations in the AMH or its receptor cause?

Answer 20

both male and female internal ducts

normal testosterone –> male external genitalia

Question 21

What is a true hermaphrodite?

Answer 21

46XX or 46XX/46XY
both ovarian and testicular tissue - ovary usually on left and ovatestes or testes on right
usually uterus (failure of AMH) - many menstruate and can get pregnant

Question 22

What is the diagnostic work-up for an infant w ambiguous genitalia?

Answer 22

karyotype, imaging of pelvis structures (ultrasound, MRI, genitography, endoscopy into sinus or pelvis), measure 17-OH-P to rule out CAH

Question 23

What is the diagnostic work-up for a post-pubertal pt w ambiguous genitalia?

Answer 23

hormone eval - LH, FSH, estradiol, testosterone