7) Hypoadrenal disorders Flashcards
What are the 3 arms of the cholesterol steroid synthesis pathway?
1) Aldosterone (mineralocorticoid)
2) Cortisol (glucocorticoids)
3) Sex steroids
What does aldosterone do?
Increase Na+ (&therefore water retention)
What does cortisol do?
Promotes glucose release
What stimulates aldosterone secretion?
Angiotensin 2
What stimulates cortisol secretion?
Stress
How is testosterone converted into oestrogen?
Aromatisation-aromatase enzyme
What are our 2 sources of sex steroids and what is the main source?
1) Gonads-main source
2) Adrenal glands
What is Addison’s disease?
Adrenal cortex fails (no cortisol/aldosterone)
3 causes of Addison’s disease?
TB (most common cause worldwide)
Autoimmunity (UK)
Congenital adrenal hyperplasia-steroid synthesis enzymes aren’t working properly
Compare what happens to the adrenal gland size in autoimmune vs congenital adrenal hyperplasia addisons:
Autoimmune addison’s=shrinks
CAH=large adrenal glands that don’t work properly
Clinical features of Addison’s:
Due to no aldosterone + cortisol
Postural hypotension
Hyponatremia
Hyperkalemia
Fatigue
Hypoglycaemia
Weight loss
Skin pigmentation
Why is skin pigmentation a feature of Addison’s disease?
As cortisol levels are low there is no -ve feedback on APG so more ACTH produced from POMC (& therefore also more MSH)
3 tests to diagnose Addison’s disease:
1) 9am cortisol (will be low + ACTH high)
2) Blood test-hyperkalemia + hyponatremia
3) Short synACTHen test
-normal-cortisol increases
Addison’s-no increase (adrenal cortex is destroyed)
4 types of congenital adrenal hyperplasia & details of each:
1) Complete 21 hydroxylase deficency (most common)
- NO CORTISOL OR ALDOSTERONE PRODUCED
- All precursors funnelled into sex steroid synthesis (hirturism/precocious puberty)
- No cortisol means there is no-ve feedback on ACTH which worsens the situation
- presents at birth
2) Partial 21 hydroxylase deficiency
- cortisol + aldosterone deficiency
- excess of sex steroids
- presents at any age
3) 11B-hydroxylase deficiency
- NO CORTISOL OR ALDOSTERONE
- All precursors funnelled into sex steroid synthesis
- -No cortisol means there is no-ve feedback on ACTH which worsens the situation
- build up of corticosterone + 11-deoxycortisol which have mineralocorticoid like effects
4) 17a-hydroxylase deficiency
- no cortisol or sex steroids made
Treatment for Addison’s disease:
IV NaCl=increase BP
Hydrocortisone-highest dose given in morning to mimic natural diurnal variation of cortisol
