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
Why do neonates not die in utero if they have 21 hydroxylase deficiency
Because they get the hormones from their mum- but once born if they have complete deficiency they’ll have an addisonian crisis- or a ‘salt losing’ crisis because they lose all their salt and become very hypotensive and die of shock
What is the age of presentation and symptom of complete 21 hydroxylase deficiency
As neonate with salt losing addisonian crisis and girls may have ambiguous genitalia (due to excess testosterone- they have a fused labia like a scrotum)- this could really indicate that they’re about to die of a salt losing crisis.
Present in 24 hrs.
So girls are VIRILISED by adrenal testosterone
Which steroids will there be an abundance of in partial 21 hydroxylase deficiency, and what will there be a lack of . Symptoms
Cortisol and aldosterone are deficient but not absent. Sex steroids and testerone in excess.
They can present at any age, as they survive at birth.
Problems with partial 21 hydroxylase deficiency
Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone
Appearance of partial 21 hydroxylase decifiency in female
Facial hair, small breasts, ACTH high, cortisol low, testosterone causes baldness and acne and clitoris enlargement and large adrenal glands, variable pigmentation, heavy muscular arms and legs
What are consequences of 11 hydroxylase deficiency
11 deoxycorticosterone (usually only in the adrenal cortex as a precursor to aldosterone) builds up, enters circulation and acts like aldosterone so binds to MR so you have hypertension and hypokalaemia, which is the opposite of what you’d expect with aldosterone deficiency!
So the kids are born with no salt losing crisis.
Their problem is with virilisation.
So virilisation, HTN and low K+
Which hormones are deficient in 11 hydroxylase deficiency and whcih in excess
cortisol and aldosterone deficient
excess is 11 deoxycorticosterone and sex steroids and testosterone.
Which hormones are deficient in 17 hydroxylase deficiency and whcih in excess
Cortisol and sex steroid deficiency
Lots of aldosterone and 11 deoxycorticosterone
Problems with 17 hydroxylase
Hypertension, low K, sex steroids deficiency, and glucocorticoid deficiency (low glucose) because enzyme is deficient in testes and ovaries too. Never go through puberty!
