Adrenal disorders Flashcards
What is the effect of angiotensin II on the adrenals?
activation of the following enzymes:
Side Chain Cleavage 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
What does aldosterone do?
Controls blood pressure, sodium and lowers potassium
What does ACTH do?
Activation of the following enzymes
Side Chain Cleavage:
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase
What is Addisons’ disease?
Primary adrenal failure
Autoimmune
destroys adrenal cortex
TB of adrenal gland is commonest cause * worldwide other than autoimmune in developed countries
Pituitary starts secreting lots of ACTH and hence MSH
Symptoms of Addisons’?
LOW SODIUM HIGH POTASSIUM LOW GLUCOCORTICOIDS
Increased pigmentation
Autoimmune vitilligo
No cortisol or aldosterone, so low blood pressure
Hypoglycaemia
Hyponatraemia
Those who have a high levels of ACTH pathologically become tanned because?
protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
What are the two causes of adrenocortical failure?
Adrenal glands destroyed
Enzymes in the steroid synthetic pathway not working
What is the congenital cause of adrenocortical failure?
Congenital adrenal hyperplasia
What are the consequences of adrenocortical failure?
- Fall in blood pressure
- Loss of salt in the urine
- Increased plasma potassium
- Fall in glucose due to glucocorticoid deficiency
- High ACTH resulting in increased pigmentation
- Eventual death due to severe hypotension
What are the tests done for Addison’s?
9am cortisol = low
ACTH = high
Short synACTHen test:
Give 250ug synacthen IM
–> Measure cortisol response
Why can we not give aldosterone to a px?
Half life of aldosterone is too short for safe once daily administration
Why can we give Fludrocortisone?
Fluorine does not exist in natural steroids, so is presence slows metabolism substantially. Binds to MR and Gr = its half life is 3.5 hours which is short but you take it 3 times a day
What is the issue with giving oral hydrocortisone?
has too short half life for daily administration, causes late peaks when can be harmful for the px
What is given instead of hydrocortisone for cortisol replacement?
prednisolone:
longer half life, more potent than cortisol, 2.3x binding affinity than cortisol
What dose of prednisolone is available?
1mg, 2.5mg, 5mg* bit much*
Not enteric coated which slows absorptions
( This would be equivalent dose of 15-25mg hydrocortisone daily )
What is the treatment of adrenal failure?
- Hydrocortisone X3 daily ( 10+5+2.5 in the day)
or
Prednisolone 3mg daily
Fludrocortisone 50 to 100 mcg daily
What causes congenital adrenal hyperplasia?
Commonest is caused bu 21 hydroxylase deficinency
Can be complete or partial
everything under 21 hydroxylase enzyme makes is missing including cortisol and aldoesterone )
What enzymes are missing in congenital adrenal hyperplasia?
everything under 21 hydroxylase enzyme makes is missing including cortisol and aldosterone )
Sex steroids are in excess as 17 hydroxylase increases testosterone = if the baby is a girl it will grow ambigous genitalia
- can’t survive even one day, the baby will be seen in hospital looking poorly
What is partial deficiency of 21 hydroxylase?
ALOT of ACTH will be made so excess testesterone
Little amount of cortisol + aldosterone so are not born to a adrenal crisis
What is the main problem 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
What is 11 hydroxylase deficiency in congenital adrenal hyperplasia?
Hypertensive and low potassium
even through deficient hormones are cortisol + aldoesterone
because 11 deoxycorticosterone behaves like aldosterone so raises blood pressure?
What is the main problem with partial 17 hydroxylase deficiency?
deficient Cortisol and sex steroids
11-deoxycorticosterone and aldosterone (mineralocorticoids) in excess
Problems :
Hypertension, low K, sex steroid deficiency and glucocorticoid deficiency (low glucose).
