gonads Flashcards
where do the female and male sex organs develop from?
gonads -> ovaries/testes
mullerian = paramesonephric ducts > female tubes, uterus, vagina
wolffian = mesonephric ducts > epididymis, vas def, seminal vesicles
external genitalia
key players in foetal male development
SRY on Y chr causes testicular development
- anti-mullerian hormone from sertoli cells
- testosterone from Leydig - stimulates wolffian duct differentiation
- dihydrotestosterone i..e androgen - develops prostate and external genitalia
foetal panhypopit vs 5alpha reductase deficiency will cause what to the foetus?
foetal panhypopit: LH causes Leydig to produce testosterone > micropenis, but normal structure
5alpha red def: makes dihydrotestosterone, so will have undervirulised male, abnormal external genitalia
when does sex determination happen in foetal life?
begins at 6 weeks
main types of isolated gonadotropin deficiency
- Kallman syndrome
- 60% less smell
-* AD/R in 85%, X-linked in 15% of KAL1 gene* - isolated gonadotropin deficiency
- normal smell, no gene
what is the hypothal-pit-gonadal axis?
hypothal = GnRH
anterior pit = LH, FSH
gonads = testosterone/oestradiol and progeserone
1’ vs 2’ hypogonadism lab tests
1’ = low T, high LH/FSH
2’ = low T, LH and FSH
extremely important syndromic causes of hyper vs hypogonadotropic hypogonadism in males
hyper i.e. 1’:
1. Klinefelter
2. Noonan
hypo i.e. 2’:
1. PWS
2. Bardet-Biedl
3. Kallman
comment on the body habitus of hypergonadotropic hypogonadism in males
eunuchoid
- epiphyses close later, so armspan»_space; height
what are the roles of FSH and LH in males vs women
Males:
FSH - sperm production
LH - causes Leydig to produce T
Females:
FSH - stimulate follicles
LH - stimulate ovulation
most common cause of primary ovarian insufficiency in females
Turner!!!
extremely important syndromic causes of primary hypogonadism in females (6)
- Turner
- Noonan
- galactosaemia
- Fragile-X - FMR1 carriers
- Ataxia-telangiectasia
- Fanconi anaemia
how to treat 1’ hypogonadism in females
estradot patches, upgrade dose slowly … likely every 6 months
2’ hypogonadism and visual problems =
septo-optic dysplasia
two most common causes of DSD with ambiguous genitalia
- CAH!
- mixed gonadal dysgenesis (46 XX/XY mosaicism) - chromosomal mosacism disturbs the differentiated of the gonads
ovotesticular dsd’s i.e. hermaphrodites are very rare
palpable gonad is most likely of what origin?
testicular - hence Y material present
palpable gonad and ambiguity =
something wrong with androgens (pituitary/testicular/adrenal)
palpable gonad + uterus / mullerian remnant present =
insufficient AMH (Sertoli cells)
thought process for an undervirilised male (46, XY DSD)
- disorder of testicular development
- Denys-Drash, WAGR, gonadal agenesis - deficiency of testicular hormones
- 17-OH deficiency - defect in androgen action
- AIS, 5-alpha reductase mutations, Smith-Lemli-Opitz
what is a way to work through a problem of DSD
- XX or XY?
- 17-OH pregnenolone /progesterone levels > CAH
- US for male/female parts
- test levels of AMH
- if male levels of AMH:
XX - test response to T
XY - test response to hCG
5-alpha reductase deficiency - key features
- 46 XY DSD - abnormal external genitalia, internal normal
- AR mutation SRD5A2
- most raised female until puberty, marked masculinisation + phallic growth
AIS - key features
- X-linked mutation in androgen receptor
- testes still develop and produce T and AMH (so no uterus/ovaries), but androgens don’t have effect
- complete = female phenotype, testes usually abdominal/inguinal
- partial = variable external phenotype, mostly male phenotype with genital ambiguity, testes usually inguinal / scrotal
- screen for malignancy
highest risk DSD of germ cell malignancy?
gonadal dysgenesis + Y chromosome + intra-abdominal gonad
key features of pubertal gyaecomastia
peaks 13-14y, regresses in 18mo
oestradiol rises before T in puberty
typically painful and tender
risk of breast cancer increased in which male patients?
Klinefelter - inc 20-60x!
