Endo 7: Hypoadrenal Disorders Flashcards
What does P450 enzyme do?
performs Side chain cleavage
how is cholesterol converted to cortisol + aldosterone ?
- start with cholesterol
- (in adrenal cortex) –> pregnenolone
- put OH group onto 17/21/11
–> forms cortisol
OR - if you put OH group onto 21/11/18 –> forms aldosterone
glucocorticoid synthesis enzymes + sex steroid synthesis enzymes = turned on by _____
glucocorticoid synthesis enzymes + sex steroid synthesis enzymes = turned on by ACTH
if pituitary detects stress –> _____ is produced
which turns on enzymes so you produce more ______
if pituitary detects stress –> ACTH is produced
which turns on enzymes so you produce more cortisol
how does cortisol production differ In the aldosterone pathway?
- renin + ATII turns on enzymes in the mineralocorticoid pathway –> to produced more cortisol
List common causes of adrenocortical failure
- Tuberculosis Addison’s Disease (Most common)
(TB grows in adrenal glands) - Autoimmune addison’s disease (most common in uk)
- congenital adrenal hyperplasia
(missing enzymes, lower level of cortisol –> so adrenal glands grow)
What happens in autoimmune addison’s disease?
- the immune system makes a mistake –> and wipes out the adrenal gland
What happens in congenital adrenal hyperplasia?
- can be complete/ partial
- caused by enzyme deficiency (commonly 21-hydroxylase deficiency) –> so adrenals can’t make hormones properly
- born with big adrenals
- adrenals can still make sex steroids due to overflow of 17 hydroxyprogesterone –> but can’t make anything else
- so cortisol + aldosterone = deficient
- testosterone = in excess (So if female, they would have abnormalities of the genitals)
List features/ symptoms of addison’s disease.
- pigmentation in mouth
- darker hair
- patches of vitiligo
- hypotension
- loss of weight
What are some consequences of adrenocortical failure?
- fall in BP
- loss of salt in urine
- increased plasma potassium
- fall in glucose due to glucorticoid deficiency
- high ACTH –> results in increased pigmentation (MSH)
Why does high ACTH result in increased pigmentation ?
POMC –> ACTH + MSH
- MSH = causes increase in pigmentation
POMC = broken down to:
POMC –> ACTH + MSH + endorphines + enkephalins + other peptides
how would you treat someone who is unconscious due to addison’s ?
inject hydrocortisone
What are some tests for addison’s
What would the results be like in a patient tie addison’s disease?
- cortisol at 9am
- test ACTH level
- short aynACTHen test
- cortisol at 9am = LOW e.g 100
- short aynACTHen test = LOW e.g 150
Describe the presentation of congenital adrenal hyperplasia
- hypotension
- virilisation (development of male physical characteristics in a female - AMBIGUOUS GENITALIA)
21 hydroxylase deficiency = recessive / dominant
21 hydroxylase deficiency = recessive
what is the difference between partial and complete 21- hydroxylase deficiency?
- same hormones will be low/high but not quite so severely.
- e.g low cortisol –> but only a little bit hypotensive
- long period of slightly raised testosterone
What happens in 11-beta hydroxylase deficiency ?
- you get build up of 11 deoxycorticosterone
- -> which is an active aldosterone receptor agonist
- so child is hypertensive, hypokalemic and virilised
What happens in 17-hydroxylase deficiency ?
- you get high levels of aldosterone
- so they are hypertensive + hypokalaemic
BUT - they are missing cortisol + sex steroids
–> so they never go through puberty - has borderline hypoglycemia
note: they don’t get addisonian crisis because they have aldosterone
Which hormones are deficient in 17-hydroxylase deficiency?
- cortisol + sex steroids
Which hormones are in excess in 17-hydroxylase deficiency?
- 11 deoxycorticosterone + aldosterone
What problems occur in 17 hydroxylase deficiency ?
- hypertension
- low K
- sex steroid deficiency
- glucocorticoid deficiency
(no cortisol, no sex steroids)
11-deoxycorticosterone behaves similarly to ________
in excess, it can cause ______ + ________
11-deoxycorticosterone behaves similarly to aldosterone
in excess, it can cause hypertension + hypokalemia
All steroids come from ________
cholesterol
note: cholesterol –> pregnenolone –> progesterone
-
pregnenolone –> progesterone via enzyme _______
dehydrogenase
How would you treat someone who comes in with falling BP + tan, lethargy?
- give them saline IV
What is synACTHen test ?
- take blood sample
- give 250 ug synacthen IM
then measure cortisol response
What is a normal cortisol level at 9am and 9.30am?
at 9am : 270-900
at 9.30 am: >600
congenital adrenal hyperplasia is most commonly due to =
- most commonly due to 21-hydroxylase deficiency
note: may be complete/ partial
in partial 21 hydroxylase deficiency, which hormones are deficient?
cortisol+ aldosterone
In martial 21 hydroxylase deficiency, which hormone are in excess
sex steroid + testosterone
how would you treat 21 hydroxylase deficiency?
give them cortisol
AT what age might 21 hydroxylase deficinecy present?
at any age
what is the effect of 21 hydroxylase deficiency on males + females?
in males = precocious puberty
in females = hirsutism, clitorial enlargement, small breasts, hyperplasia of adrenal cortex
what is the effect of 11 hydroxylase deficiency?
high bp
high level of sex steroids
no aldosterone
no cortisol
11 deoxycorticosterone acts similarly to _____
aldosterone
in 11 hydroxylase deficiency, hormone deficient =
cortisol
aldosterone
in 11 hydroxylase deficiency, hormone in excess=
sex steroid, testosterone
what is the main problem in 17 hydroxylase deficiency?
- no growth spurt
- no puberty
- and also presents with hypertension
how would you treat a patient with 11 hydroxylase deficiency?
- give them hormone replacement
e. g testosterone, oestrogen etc.
Draw a diagram showing the processes involved in the conversion of cholesterol to
a) aldosterone
b) cortisol
c) sex steroids
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