Disorders of Sexual Differentiation Flashcards
What is gonadal dysgenesis?
Sexual differentiation is incomplete.
e.g.
A missing SRY in male
Partial/complete deletion of second X chromosome
What is sex reversal ?
Phenotype does not match the genotype.
Male genotype with female external
What is the definition of Intersex?
Components of both genital tracts are present or ambiguous genitalia
What would happen if a individual has XY
Testosterone is made but has no effect ?
Androgen insensitivity syndrome
What happens in Androgen insensitivity?
Testes will form and make AMH which causes Mullerian duct regression as there is an SRY gene
Testosterone not working means that there is no Wolffian duct differentiation
They will have no uterus/fallopian tubes
External genitalia will appear female
Primary amenorrhoea(lack of menstrual cycle)
What is the outcome of Partial AIS?
The spectrum of phenotypes do vary:
Some have almost normal female external genitalia
Male features are not obvious but at puberty as testosterone levels increase these may become more masculinised.
What will happen in the case of a XY male who is unable to make /respond to AMH in utero?
Persistent Mullerian duct syndrome
What mutations can cause Persistent Mullerian duct syndrome?
PMDS type 1 is due to a mutation of the gene for AMH on chromosome 19
PMDS type 2 from mutation of gene for AMH receptor (AMH-RII) chromosome 12
What will be the outcome of PMDS?
Testes will form as SRY is present but fail to make AMG /or AMH receptor may be absent.
Result= Mullerian ducts remain
Differentiation of Wolffian ducts and masculinised external genitalia
What genitalia do individuals with PMDS have ?
The result is a intra-abdominal mullerian structure and testes in a position instead of ovaries
(Inguinal sac)
Some have one testis in a hernial sac /scrotum together with Mullerian structure
(Hernia uteri inguinalis)
10% have testes both located in hernial sac (transverse testicular ectopia) along with uterine tubes and uterine structures
May lead to malignancy
What treatment options are available for PMDS
Surgery to retrieve testes and position in scrotum
(Testosterone replacement at puberty if testes cannot be retrieved)
Removal of uterus dissection of Mullerian tissue away from Vas deferens /epididymis
Laparoscopic hysterectomy to prevent neoplastic tissue formation
What will happen if an XY individual has testosterone but not DHT ?
5 alpha reductase deficiency.
due to a problem with the 5 alpha reductase gene
What will happen in 5 alpha reductase deficiency
SRY means there will be the regression of Mullerian ducts due to the release of AMH.
Testosterone will lead to development of the Wolffian ducts and seminal vesicles and vas deferens.
Lack of DHT means no male external genitalia.
What symptoms can be detected with 5 alpha reductase deficiency ?
Have ambiguous genitalia, such as labioscortal folds, clitoridean penis
Levels of testosterone needs to be assessed during puberty , adrenarche - may cause virilisation (
What is Virilisation?
Women developing male hair growth patterns
What is 45XO?
Turners syndrome
What will Turners syndrome cause ?
They have ovarian dysgenesis Streak ovaries (Both X chromosomes are required for normal ovarian development)
Uterus /tubes are present
May be fertile , may have mosaicism
Issues with hormone support of bones and uterus
What causes Mosaicism in females ?
This is as a result of X inactivation or no X chromosome.
Depends on when that X chromosome may have been lost which means that some cells will have it whilst others do not .
What will happen when a XX female is exposed to high levels of androgens in utero ?
Congenital adrenal hyperplasia
Outline the hypothalamic pituitary adrenal axis
Hypothalamus
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CRH (corticotrophin-releasing hormone )
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Pituitary
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ACTH (Adrenocorticotropic hormone)
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Adrenal glands (Make cortisol +negative feedback)What does corticotropin releasing hormone do ?
Stimulate pituitary to secrete ACTH
What does Adrenocorticotropic hormone do ?
Stimulate rapid uptake of cholesterol into the adrenal cortex
Upregulates cholesterol side-chain cleavage enzyme
Increases glucocorticoid secretion
What happens to the HPA axis in congenital adrenal hyperplasia?
There is no production of cortisol which means there is no negative feedback loop which leads to a increase of androgens.
Granulosa cells do not yet express aromatase which causes a build up.
How would a CAH patient be treated ?
Glucocorticoids
No aldosterone is made which causes salt wasting
