B8-059 Disorders of Sex Development

Question 1

most common cause of male hypogonadism

Answer 1

klinefelter syndrome

Question 2

gyencomastia
tall
less body hair
small, firm testes

Answer 2

klinefelter syndrome

Question 3

in klinefelters, the […] do not enlarge and undergo fibrosis, resulting in small firm testes and azoospermia

Answer 3

seminiferous tubules

Question 4

why do patients with klinefelter’s exhibit declining T levels and elevating LH secretion?

Answer 4

leydig cells become progressively deficient

Question 5

streaked ovaries

Answer 5

Turners

(normal tissue replaced by fibrous tissue –> gonadal dysgenesis)

Question 6

why should cryptorchidism be corrected? [3]

Answer 6

increased risk of germ cell tumors
increased risk of torsion
impaired fertility

Question 7

mutations in AMH or it’s receptor (AMHR-2), result in

Answer 7

46 XY, PMDS

(persistent mullerian duct syndrome)

Question 8

absence of sertoli cells or AMH would result in

Answer 8

both male and female internal genitalia with streak gonads

male external genitalia

Question 9

absence of 5-a reductase would result in

Answer 9

male internal genitalia
female/atypical external genitalia until puberty

(cannot convert T to DHT)

Question 10

[…] duct gives rise to internal male genitalia

Answer 10

mesonepheric

Question 11

[…] duct gives rise to internal female genitalia

Answer 11

paramesonepheric

Question 12

presence of SRY gene activates […] and […] cells and ultimately leads to the formation of male external genitalia

Answer 12

leydig (mesonepheric ducts persist)
sertoli (paramesonepheric ducts degenerate)

Question 13

absence of SRY gene activates […] and […] cells and ultimately leads to the formation of female external genitalia

Answer 13

thecal (mesonepheric duct degenerates)
follical (paramesonepheric persists)

Question 14

when SRY is present, leydig cells produce […] which allows for mesonepheric duct to persist

Answer 14

testosterone

Question 15

when SRY is present, sertoli cells produce […] which allows for paramesonepheric duct to degenerate

Answer 15

AMH

Question 16

testicular descent into the scrotum is dependent on […]

Answer 16

INSL3 and T

Question 17

SRD5A1 is the gene for […]

Answer 17

5-a reductase

Question 18

what hormones drive development of the labioscrotal folds and clitorophallus?

Answer 18

T and DHT

Question 19

[…] cause the urethral plate to give rise to the penile urethra

Answer 19

androgens

Question 20

testes present
but external genitalia feminized or atypical

most commonly caused by androgen insensitivity syndrome

Answer 20

46 XY DSD

Question 21

ovaries present
external genitalia are virilized/atypical

most commonly due to congenital adrenal hyperplasia

Answer 21

46 XX DSD

(due to excessive exposure to androgens in early development)

Question 22

markedly elevated 17-hydroxyprogesterone is diagnostic for

Answer 22

CAH

Question 23

in CAH, if a deficient enzyme starts with 1, it causes

Answer 23

hypertension

Question 24

in CAH, if a deficient enzyme ends with 1 it causes

Answer 24

virilization in females

Question 25

ovotesticular DSDs are most commonly observed in individuals with [...]

Answer 25

mosaicisms (46, XX/ 46XY karyotype)

Question 26

ovotesticular DSD is more common in 46 [...]

Answer 26

46,XX

Question 27

both ovarian and testicular tissue present atypical genitalia

Answer 27

ovotesticular DSD

Question 28

most patients with 46 XX DSDs have normal testicular function but are infertile due to [...] defect

Answer 28

spermatogenic

Question 29

translocations of [...] can block the female pathway and drive testicular development

Answer 29

SRY (results in 46XX SRY+)

Question 30

mutations in RSPO1 or WNT4 can allow for partial or complete [...] development in 46 XX SRY- DSD patients

Answer 30

testis typically, RSPO1 and WNT4 inhibit SOX9, inducing female pathway

Question 31

46, XX SRY- DSD is typically a result of translocation of [...] gene

Answer 31

SOX9 typically, RSPO1 and WNT4 inhibit SOX9, inducing female pathway

Question 32

defect in androgen receptor resulting in female appearing genetic male

Answer 32

androgen insensitivity syndrome (46, XY DSD)

Question 33

testes present and functional blind vaginal pouch no T or DHT activity (no hair)

Answer 33

complete androgen insensitivity syndrome (46, XY DSD)

Question 34

46, XY DSDs are [...] virilized

Answer 34

under

Question 35

46, XX DSDs are [...] virilized

Answer 35

over

Question 36

one of the most common causes of atypical genitalia in newbowns

Answer 36

21-hydroxylase deficiency

Question 37

classic CAH is characterized by [hormone] deficiency

Answer 37

cortisol (75% are salt-losers due to aldosterone)

Question 38

SRY activates [gene]

Answer 38

SOX9

Question 39

SOX9 and FGF9 destabilize [...] to inhibit ovarian development

Answer 39

b-catenin

Question 40

[...] induces and maintains sertoli cell differentiation

Answer 40

SOX9

Question 41

sertoli cells induce leydig cell development. leydig cells induce [...]

Answer 41

NR5A1

Question 42

stabilize b-catenin and induce the ovarian pathway [2]

Answer 42

RSPO1 and WNT4

Question 43

[...] induces granulosa cell differentiation

Answer 43

FOXL2

Question 44

treatment for 21-hydroxylase deficiency

Answer 44

dexamethasone

Question 45

low T and poor response to hCG normal AMH high LH/FSH absent paramesonephric derivatives

Answer 45

leydig cell hypoplasia

Question 46

reduced T and INSL3 would be consistent with

Answer 46

undescended testes

Question 47

enhanced SOX9 levels in XX individuals drive [...] development

Answer 47

testis (but no Y chromosome, so testes don't make sperm=infertility)

Question 48

a mutation that modestly impacts the WNT pathway would result in

Answer 48

ovotestes (only partially divert ovarian pathway)

Question 49

what is the most likely presentation for an individual with 46, XY DSD with inactivated SRY?

Answer 49

streaked gonads female external genitalia uterus SRY inactivation= gonad dysgenesis also no production of AMH/MIS = female genitalia

Question 50

NR5A1 mutations cause [...] dysgenesis

Answer 50

testes (no sertoli/leydig cells --> no AMH --> female)

Question 51

RSPO1 mutations divert the ovarian pathway to the testicular pathway by destabilizing [...]

Answer 51

b-catenin

Question 52

complete loss of RSPO1 function would result in

Answer 52

testis development infertility

Question 53

partial loss of RSPO1 function would result in

Answer 53

ovotestes