Hypoadrenalism Flashcards
How many carbon atoms does cholesterol have?
27
What determines which steroids the different parts of the adrenal gland produce?
The combination of enzymes present in the different parts of the adrenal gland – hydroxylation in different positions of the cholesterol molecule gives different products.
Which enzyme converts cholesterol to pregnenolone?
Cytochrome P450 (short chain cleavage)
Which sets of enzymes are switched on by ACTH?
Cortisol synthesis enzymes
Sex steroid synthesis enzymes
The pituitary gland produces ACTH in response to what?
Stress
Which enzyme converts corticosterone to aldosterone?
Aldosterone synthase (includes 18-hydroxylase)
State three causes of adrenocortical failure.
Tuberculous Addison’s Disease – most common cause worldwide
Autoimmune Addison’s Disease – most common cause in the UK
Congenital Adrenal Hyperplasia
State some consequences of adrenocortical failure.
Hypotension (due to lack of aldosterone)
Hyperkalaemia
Loss of salt (sodium) in urine
Fall in blood glucose (due to lack of cortisol)
High ACTH –> pigmentation
Vitiligo
Eventual death due to severe hypotension
Why do Addison’s patients get vitiligo?
Vitiligo is an autoimmune disease where you have antibodies against melanin
Autoimmune diseases tend to go hand-in-hand
Why does Addison’s cause skin pigmentation?
The lack of cortisol stimulates the production of huge amounts of ACTH.
ACTH is formed from the cleavage of POMC (pro-opiomelanocortin) to ACTH and alpha-MSH High ACTH also means high alpha-MSH –> skin pigmentation
State some tests for Addison’s disease.
9 am cortisol (this should be high in a normal person)
You could measure ACTH and this should be high in Addison’s Inject synthetic ACTH (synacthen) and if they have functioning adrenals, they should start to produce cortisol
NOTE: 250 mg IM synacthen
What is the most common cause of congenital adrenal hyperplasia (CAH)?
21-hydroxylase deficiency
What are the two degrees of CAH?
Partial or Complete (absence of the enzyme)
Why are foetuses with CAH normally fine in utero?
In utero, the foetus’ will have maternal cortisol and aldosterone so don’t need to rely on their own endogenous production.
Which hormones are absent in complete 21-hydroxylase deficiency?
Cortisol and Aldosterone
What effect does 21-hydroxylase deficiency have on sex steroid synthesis?
It funnels the precursors towards the steroid synthesis pathway so you get an increase in adrenal sex steroids.
What are the two main features of 21-hydroxylase deficiency?
Hypotension
Virilisation (female babies will be born with ambiguous genitalia)
Describe the presentation of partial 21-hydroxylase deficiency.
They may present much later because they don’t have a salt losing Addisonian crisis.
They will present once they start to see the effects of the excess adrenal sex steroids e.g. hirsuitism and precocious puberty They will also be a little hypotensive
Describe and explain the presentation and explanation of complete 11-hydroxylase deficiency.
With 11-beta hydroxylase deficiency there will be a build-up of 11-deoxycorticosterone
11-deoxycorticosterone has mineralocorticoid effects so they don’t have a salt losing Addisonian crisis – they will behave as if they have HIGH aldosterone
They will be HYPERTENSIVE and HYPOKALAEMIC
There will still be some funnelling towards the sex steroid synthesis pathway so the child will also be VIRILISED
NOTE: boys may be missed because they tend to look normal
Describe and explain the presentation of 17-hydroxylase deficiency.
They will have high levels of aldosterone meaning that they are hypertensive and hypokalaemic
They are missing cortisol and sex steroids so they will not go through puberty
They will usually present around pubertal age – they will be hypertensive, have borderline hypoglycaemia and absent puberty
NOTE: they will also have a lot of infections because you need cortisol to cope with the stress of infections
What will happen to a baby with complete 21-hydroxylase deficiency after they are born?
They will have a salt losing Addisonian crisis due to the lack of aldosterone
