Hypoadrenal disorders Flashcards
How many carbons does cholesterol have?
27
How do you get different substances from cholesterol?
You hydroxylate it at different positions
What is the most common cause of adrenocortical failure worldwide?
Tuberculous Addison’s disease–common in developing
What is the most common cause of adrenocortical failure in the UK?
Autoimmune Addison’s disease- immune system makes a mistake and wipes out adrenal gland
What is congenital adrenal hyperplasia?
When you are born with big adrenal glands and that is caused by enzyme deficiency so the adrenals can’t make the hormones properly
How do Addison’s patients present?
They have darker hair, increased skin pigmentation and in scars and gums and patches of vitiligo (not unique for Addisons just indicates an autoimmune disorder), exhaustion (reduced cortisol), weight loss,
Postural hypotension
Where is vitiligo also seen
Appearance of adrenal glands
What are the consequences of adrenal failure?
Addisons, primary hypotension, Graves-> hypertension
Appearance of adrenal glands:
If due to autoimmune- Shrunk
If due to TB- granulatamous
Destruction of adrenal cortex only really affects aldosterone and cortisol
-Androgens less so as they are primarily made at gonadal organs
Fall in blood pressure- no aldosterone
Loss of salt in urine- unable to retain salt due to lack of aldosterone
Increased plasma potassium
Fall in blood glucose- glucocorticoid deficiency
High ACTH resulting in increased pigmentation (ACTH–> Cortisol)
Eventual death due to severe hypotension- if it happens suddenly its an Addisonian crisis
What are the two components of POMC (pro-opiomelanocortin)
ACTH and MSH
Explain the link between adrenal failure and increased pigmentation?
Due to adrenal gland failure, there is no cortisol which means that there is no negative feedback on ACTH so there is high ACTH and ACTH is formed in the pituitary by POMC being broken down into ACTH and MSH so there is also high MSH and increased pigmentation
How do you test for Addison’s?
Measure the hormones at 9 am and their cortisol should be high, if it’s not they might have Addison’s
You could measure their ACTH and that should be really high
You could inject them with synthetic ACTH (synacthen) and they should make a lot of cortisol in response if normal
How does the 9am cortisol of an Addison’s patient compare to the normal range?
Low- around 100 (normal is 270-900)
What is the commonest cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
Is congenital adrenal hyperplasia evident in utero?
No because you receive the hormones from your mother
What hormones can someone with 21-hydroxylase not produce?
Cortisol and aldosterone
What happens to sex steroids in someone with 21 hydroxylase deficiency?
They can still make them because there is an overflow of 17-hydroxyprogesterone, they will make a lot of sex steroids but can’t make anything else
What happens if cortisol and aldosterone are completely absent?
few weeks
What is the first thing a doctor would do to treat congenital adrenal hyperplasia?
Give IV saline- good because you’ve lost salt
Why do congenital adrenal hyperplasia have genital defects?
Excess testosterone- especially noticeable in girls
How does congenital adrenal hyperplasia present?
Hypotension
Virilisation
Abnormality of genitalia
What is virilisation?
Development of male characteristics in a female
What happens in partial 21-hydroxylase deficiency? which hormones are deficient, which hormones are in excess
What happens as a result of this deficiency in boys
You’ll have low cortisol and aldosterone and be a little hypotensive but won’t die and will have a long period of slightly raised testosterone
Excess of sex steroids, testosterone,
Precocious puberty in boys
What happens in 11 beta hydroxylase deficiency? which hormones are in excess and which hormones are deficient
present with
Function of aldosterone
Aromatase used for the conversion of what to what
Aldosterone produced from what
You get build up of 11 deoxycorticosterone
and sex steroids and testosterone
Deficient in cortisol and aldosterone
virilisation, hypertension and low k
Absorp Na
Testosterone to oestrogen
Angiotensin 2
What is 11 deoxycorticosterone?
precursor to aldosterone, behaves like aldosterone
in excess causes hypertension and hyperkalaemia
How does 11 beta hydroxylase deficiency present?
You don’t have a salt losing Addisonian crisis but behave like they have a high level of aldosterone due to high 11 deoxycorticosterone (precursor of aldosterone) so:
Hypertensive in childhood
Hypokalaemic
Virilised
What happens in 17 beta hydroxylase deficiency? which hormones are deficient
Hormones in excess
Cortisol and sex steroids
High aldosterone and 11 deoxycorticosterone
High levels of aldosterone (hypertensive and hypokalaemic) but no cortisol and sex steroids so will never go through puberty and are borderline hypoglycaemic (deficient glucocorticoid)
