Hypoadrenal Disorders Flashcards
Starting precursor for steroid synthesis?
Cholesterol
What are the 3 main pathways in steroid synthesis
Mineralcorticoids - aldosterone
Glucocorticoids - cortisol
Androgens - sex steroids
Main enzyme group resulting in the different structures forming in steroid hormone biosynthesis?
Dehydrogenases
Which of the pathways in steroid synthesis is not as important?
Androgens - main source is the gonads NOT the adrenal!
Which hormones are under ACTH control?
Cortisol & Androgens
Which hormone is NOT under ACTH control?
Aldosterone - AGTII controls it
Which enzymes should be remembered in the steroid synthesis pathway (ONENOTE!!)?
17, 21, 11 & 18
HYDROXLYASES
2 causes of adrenocortical failure?
- Adrenal glands are destroyed (develop this)
2. Enzymes in the steroid synthetic pathway do not work (born with)
3 potential causes of adrencortical failure when the adrenal glands are destroyed?
- TB causes Addison’s disease (common in developing)
- Autoimmune causes Addison’s (common in developed)
- Congenital adrenal hyperplasia
Signs & symptoms of adrenocortical failure?
Loss of aldosterone:
- Hypotension
- Loss of salt in urine
- Hyperkalaemia
Loss of cortisol:
- Hypoglycaemia
- Hyperpigmentation [POMC –> ACTH + MSH] (as high ACTH)
Eventual death due to severe hypotension
Vitaligo?
Destruction of melanocytes (not just specific to Addison’s)
Shows have AUTOIMMUNE dysfunction
What happens to the adrenal medulla in adrenocortical failure?
It is UNAFFECTED - only ACTH is attacked due to autoimmune
What is POMC broken down into?
ACTH + MSH
And endorphins, enkephalins and other peptides
Common indication if have Addison’s when seen in hospital?
LOW Na+
HIGH K+
Initial test for Addison’s?
9am cortisol = LOW (should be high)
ACTH = HIGH
Test carried out for Addison’s followed by the initial test?
Short synacthen test
synACTHen
How does the short synacthen test work?
Synacthen - synthetic ACTH
Injection of 250ug of synacthen IM - this is a large dose so should induce a LARGE response in healthy individuals
What will be seen in the short synacthen test in a person suffering from Addison’s?
Cortisol SHOULD increase
If cortisol response barely changes (i.e. 100 to 150) confirms Addison’s
CAH?
Congenital Adrenal Hyperplasia
2nd cause of adrencocortical failure
4 types of CAH?
x Complete 21-hydroxylase deficiency
x Partial 21-hydroxylase deficiency
x 17-hydroxylase deficiency
x 11-hydroxylase deficiency
What does complete 21-hydroxylase deficiency lead to?
NO production of aldosterone OR cortisol
EXCESS of sex steroids (no -ve feedback)
Most common cause of CAH?
COMPLETE
21-hydroxylase deficiency
Age of presentation of complete 21-hydroxylase deficiency?
Present in neonates - as a salt-losing Addisonian crisis
Before birth, in utero - fetus receives steroids from mother across placenta so not an issue
Survival rate and presentation in those with complete 21-hydroxylase deficiency?
Survival - <24hrs
Girls present more obviously - virilisation (ambiguous genitalia due to excess testosterone) & may have clitoromegaly
