The Adrenal Gland And Hypoadrenalism Flashcards
What are steroid hormones?
Made from cholesterol
They are made in the adrenal cortex
Corticosteroids include:
Mineralocorticoids (aldosterone)
Glucocorticoid (cortisol)
Sex steroids (androgens and oestrogens)
What is the effect of angiotensin II on the adrenal glands?
Activation of the enzymes: Side chain cleavage 3 hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
Ie. Angiotensin II turns cholesterol into aldosterone
In the zona glomerulosa
What is the action of aldosterone?
Raises blood pressure
Increases sodium regulator in the kidneys
Lowers potassium levels
What are the effects of ACTH on the adrenal glands?
Activation of: Side chain cleavage 3 hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 17 hydroxylase
Leads to the production of cortisol
In the zona fasciculata
What is an enzyme?
A protein
Catalyses a specific reaction
Specific enzymes catalyse the synthesis of particular alteration to the molecule (eg. 21 hydroxylase)
What are the enzymes involved in steroid synthesis and the steps?
Please please please look at the note bank
But
Both have side chain cleavage, then 3-hydroxysteroid dehydrogenase
Aldosterone is:
21, 11, 18
Cortisol is:
17,21,11
How is cortisol released?
Diurnal rhythm
Lowest at 12
Peaks around 8am
So we measure cortisol at 9am
What is Addison’s disease?
Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (most common in the UK)
Or TB of adrenal glands (most common worldwide)
Pituitary starts secreting loads of ACTH due to lack of negative feedback
Reduced sodium reabsorbtion so lower blood pressure
What are the symptoms of Addison’s disease?
Hyperpigmentation Low blood pressure Weakness Weight loss Nausea Diarrhoea Vitiligo
What are the symptoms of adrenal crisis?
Fever Syncope Convulsions Hypoglycaemia Hyponatremia Severe vomiting and diarrhoea
Why does addisons cause hyperpigmentation?
Pro-opio-melanocortin (POMC) is the precursor protein that is cleaved to form both ACTH and MSH
Therefore they are co-secreted
Lack of cortisol means lack of negative feedback so lots of ACTH is secreted, so lots of MSH (melanocyte stimulation hormone) is also secreted
Which tans the skin
Hypoadrenalism can cause BOTH hyperpigmentation and vitiligo
What are the causes of adrenal failure?
Destruction of adrenal glands:
- Autoimmune Addison’s disease
- Tuberculosis Addison’s
Enzymes in the steroid synthetic pathway not working:
Congenital adrenal hyperplasia
What are the consequences of adrenalcortical failure?
Fall in blood pressure
Loss of salt in 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 for Addison’s disease?
9am cortisol - should be low
ACTH - should be high
Short synACTHen test -
Give 250ug of synacthen IM
Measure cortisol response-
If no cortisol is produced, Addison’s is confirmed
How is Addison’s treated?
Aldosterone replacement:
(Half life of aldosterone is too low for safe once daily administration)
FLUDROCORTISONE- fluorine is it present in natural steroids. So this slows down the drugs metabolism.
It binds to both mineralocorticoid and glucorticoid receptors
Given once daily (50-100 mcg)
Cortisol replacement:
Hydrocortisone has too short a half life to be administered once daily
PREDNISOLONE - it has a double bond where cortisol doesn’t. This gives it a longer half life and makes it more potent and double the binding affinity
Administered once daily (3-4mg)
(Hydrocortisone can be used instead but it has to be given 3 times daily)
