Disorders of Sexual Development Flashcards
Turner Syndrome: pathophysiology
45XO
“streaky gonads” ovaries only have stromal tissue, so not able to produce hormones
Turner Syndrome: epidemiology
most common chromosomal abnormality in women
Turner Syndrome: Associated conditions
coarctation of aorta
IBD
renal abnormalities
deafness
endocrine (autoimmune thyroiditis)
Turner Syndrome: clinical features
short stature
wide-spaced nipples
webbed neck
wide hips
primary amenorrhoea
Turner Syndrome: management
in childhood, the aim is to promote GROWTH
in adolescence, the aim is to initiate PUBERTY
pregnancy only possible with ovum donation
What is the pathophysiology of COMPLETE 46,XY gonadal dysgenesis
mutation of SRY gene of Y chromosome => do not form testis
“streaky gonads” - only stromal tissue
no testosterone –> so no virilisation (female external genitalia)
no AMH –> uterus, cervix and vagina form
result: phenotypically female, but XY karyotype
How is COMPLETE 46,XY gonadal dysgenesis managed
dysgenetic gonad laparascopic removal –> risk of malignancy
What is the pathophysiology of MIXED 46,XY gonadal dysgenesis
20% have mosaic XX/XY
gonads have testicular and ovarian tissue (ovotesticular DSD) –> ambiguous external genitalia
What is the most common cause of 46,XY DSD?
Complete Androgen Insensitivity Syndrome
CAIS: pathophysiology
46,XY karyotype
testicular tissue forms –> testosterone and AMH produced
Androgen receptors not responsive to Testosterone –> no virilisation of external genitalia
result: female external genitalia with testis internally (~within inguinal canal)
CAIS: clinical features
primary amenorrhoea
CAIS: management
testis need to be resected –> small risk of malignancy
once testis removed –> HRT
vaginal shortening and dilation
PAIS: pathophysiology
46,XY karyotype
Androgen receptors partially responsive to testosterone –> ambiguous external genitalia
What is the most common cause of 46,XX DSD?
Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia: pathophysiology
21-B-hydroxylase deficiency
Progesterone cannot be converted to:
- 11-deoxycorticosterone (–>aldosterone)
-11-deoxycortisol (cortisol)
Low FETAL serum cortisol –> negative feedback to adrenal gland –> hyperplasia
Adrenal hyperplasia causes excessive adrenal androgen production –> virilisation of female fetus
2/3 also have reduced aldosterone production (‘salt-losing baby’)
Congenital Adrenal Hyperplasia: management
Hydrocortisone (replace cortisol)
Fludrocortisone (if ‘salt-losing’)
Feminising surgery
