CM: Disorders Sex Differentiation Flashcards Preview

Block 8 - Endo & Repro > CM: Disorders Sex Differentiation > Flashcards

Flashcards in CM: Disorders Sex Differentiation Deck (23)

What is the role of AMH in sexual differentiation?

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


What is the role of testosterone in sexual differentiation?

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


What is the role of DHT in sexual differentiation?

promotes dev of external male genitalia


What are critical concepts related to in utero development?

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


What is the role of testosterone at puberty?

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


What does DHEA-S do during puberty?

dev of sexual hair pattern (axillary and pubic)
does not depend on functioning gonads


What is the role of estrogen at puberty?

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


What is gonadal dysgenesis?

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


What are the features of Klinefelter's syndrome?

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


What are the features of Turner's syndrome?

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


What are the features of mixed gonadal dysgenesis?

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


What is gonadal dysgenesis w a normal karyotype?

specific gene defects
mutations in SF-1 that regulates SRY --> gonadal and adrenal agenesis


What are 46XX DSD?

female genotype w male genotype - CAH or elevated maternal androgens


What is the presentation of 46XX DSD?

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


What can cause elevated maternal androgens?

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


What is 46XY DSD?

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


What can cause impaired androgen responsiveness?

mutations in receptor or 5alpha-reductase def
testes dev and produce AMH and testosterone


What is androgen insensitivity syndrome?

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


What is 5alpha-reductase def?

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


What do mutations in the AMH or its receptor cause?

both male and female internal ducts
normal testosterone --> male external genitalia


What is a true hermaphrodite?

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


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

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


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

hormone eval - LH, FSH, estradiol, testosterone