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?
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
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