Hypoadrenal Disorders Flashcards
Outline the basic steroid biosynthesis pathways
cholesterol->progesterone (cytochrome p450) -> 17a OH pregn. (17a hydroxylase) -> SEX STEROIDS (aromatase)
17aOH pregn.-> 11 deoxycortisol (21 hydroxylase)->CORTISOL (11 b hydroxylase)
progesterone -> 11 deoxycorticosterone (21 hyd.) -> corticosterone (11 b hyrd.) -> ALDOSTERONE (18 hydroxylase)
*17,21,11,18
What are some common causes of adrenocortical failure?
- Adrenal glands destroyed :
- Tuberculosis Addison’s disease - most common worldwide.
- Autoimmune Addison’s disease - most common in the UK.
- Congenital adrenal hyperplasia – gland overgrows but does not function properly. - Enzymes in the steroid synthetic pathway not working
What are the consequences of adrenocortical failure?
- Hypotension (loss of aldosterone)
- Loss of salt in the urine (loss of aldosterone)
- Hyperkalaemia (loss of aldosterone)
- Hypoglycaemia – due to glucocorticoid deficiency.
- High ACTH hyperpigmentation.
- > High ACTH due to loss of negative feedback by cortisol on the pituitary.
- > POMC ACTH + MSH (leading to hyperpigmentation even inside mouth) - also breaks down into endorphins, enkephalins and other peptides.
- Eventual death due to severe hypotension
How can you test for Addison’s disease?
An Addison’s suffering patient would have blood levels like this:
- 9am Cortisol = 100 LOW (normal range: 270-900)
- ACTH = HIGH
The test we then use is the Short synacthen test.
- Give 250 micro g of synacthen (synthetic ACTH) IM – this is a LARGE dose of ACTH and should induce a LARGE response in a healthy individual.
- Measure the cortisol response.
- If the cortisol response barely changes (e.g. goes from 100 to 150 - should be >600) they have Addison’s
What are the different types of congenital adrenal hyperplasia (CAH)?
- Complete 21-hydroxylase deficiency
- Partial 21-hydroxylase deficiency
- 11-hyroxylase deficiency
- 17-hydroxylase deficiency
What happens in complete 21-hydroxylase deficiency?
- recessive
- MOST common cause of CAH.
- Comes in complete and partial forms.
- Leads to NO production of aldosterone or cortisol but EXCESS of sex steroids (no negative feedback)
Presentation:
- Children with this will present at 1 week-old.
> This will usually be in the form of a salt losing Addisonian crisis.
> In-utero the child will be fine as they receive steroids from the mother.
> Girls present more obviously than boys due to ambiguous genitalia (virilisation) and may have clitoromegaly
What happens if you have a partial 21-hydroxylase deficiency?
Hormones deficient:
- Cortisol
- aldosterone.
Hormones in excess:
- Sex steroids
- testosterone
Age of presentation:
- Any age (as they survive).
- The main problem is in later life with hirsutism and virilisation in girls and precocious puberty in boys.
Symptoms and signs include:
- Acne
- facial hirsutism
- small breasts
- clitoral enlargement
- heavy arms/legs
What happens if you have an 11-hyrdoxylase deficiency?
- XS 11 deoxycortisone - 11-deoxycortisone behaves like aldosterone and so in excess (accumulation in zona glomerulosa) it can cause hypertension and hypokalaemia.
Hormones deficient:
- Cortisol
- aldosterone
Hormones in excess:
- Sex steroids
- testosterone
- 11-deoxy corticosterone.
Symptoms and signs:
- Virilisation
- hypertension
- hypokalaemia.
What happens in 17-hydroxylase deficiency?
Hormones deficient:
- Cortisol
- sex steroids.
Hormones in excess:
- 11-deoxy corticosterone
- aldosterone (the mineralocorticoids).
Symptoms and signs:
- Hypertension, hypokalaemia
- sex steroid deficiency
- glucocorticoid deficiency (leading to hypoglycaemia).
