Endo 7: Hypoadrenal disorders Flashcards
Why is it called ACTH?
Trophic means growth! So it makes the adrenal gland hypertrophy as well as release cortisol
What does ACTH do
Switches on enzymes in the zona fasciculata which allow cortisol production (17 alpha hydroxylase, 3b-HSD, 21 hydroxylase and 11beta hydroxylase). For aldosterone, RAAS activates these enzymes
Pathway of aldosterone from progesterone
progesterone –>(by 21 hydr.) 11 deoxycorticosterone –> (by 11 hydroxy) corticosterone –> (by 18 hydrox.0 aldosterone
Pathway of progesterone to cortisol
progesterone –>(by 17 hydrox.) 17OH progesterone –> (by 21) 11 deoxycortisol –> (by 11) cortisol
Causes of adrenocortical failure
2 forms o
- adrenal glands being destroyed
- steroid synhesis enzyme deficiency
Most common cause of adrenocortical failure (in world)
Tuberculous Addison’s disease
Other form of adrenal gland destruction
Autoimmune Addison’s disease (commonest in UK)
What disease results from steroid synthesis enzyme deficiency
Congenital adrenal hyperplasia (born with huge glands as they are stimulated by ACTH but have an enzyme deficiency so cannot produce it!)
Consequences of adrenocortical failure
Hypotension (not enough aldosterone)
Loss of salt to the urine
Increase plasma K+
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Vitiligo (another autoimmune disease)–> really stark in addisons because antibodies wipe out melanocytes (giving pale area) and really dark area because of the stimulate melanocytes)
Why are addisons patients tanned
POMC –> MSH and ACTH and endorphins and enkephalins and other peptides
So because all the ACTH is being made as there’s no negative feedback due to lack of cortisol, lots of MSH is being released and this is stimulating melanocytes and leading to tanning.
Why is addisons dangerous
Blood pressure keeps falling because you’re losing loads of salt (due to lack of aldosterone) so you die
How do you test for addisons
- You test ACTH in the morning.
At 9am, cortisol is normally to be high, so ACTH should be low. If the cortisol is low and ACTH high at 9am, then you need to investigate further. Normal cortisol at 9am (270-900nm), so addisons might be 100nm. - SynACTHen test
Give them 250ug im synACTHen. The cortisol should increase to over 600nm. If it increased from 100nm –> 150nm, it would be a fail and then they have addisons
Commonest cause congenital adrenal hyperplasia
21 hydroxylase deficiency (recessive condition) –> complete and partial
Differentiate effect of complete and partial hyperplasia
if complete- only 24 hours to live because you have no aldosterone and no cortisol
If partial
Which steroids will there be an abundance of in complete 21 hydroxylase deficiency, and what will there be a lack of
excess sex steroids especially testosterone (so very virilised- and you get floppy baby)
lack of cortisol and aldosterone
So they cannot retain any salt or make any sugars