Endo - Adrenal Disorders 1 Flashcards
What are steroids derived from?
Cholesterol
What does the adrenal cortex produce?
Corticosteroids
What does the zone glomerulosa produce?
Mineralocorticoids
What does the zona fasciculata produce?
Glucocorticoids
What does the zona reticularis produce?
Sex steroids
What does angiotensin 2 activate?
Side chain cleavage 3-Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
What does angiotensin 2 cause?
Aldosterone production
How does aldosterone act?
Increases Na reabsorption and K excretion therefore controls blood pressure
What does ACTH activate?
Side chain cleavage 3 hydroxysteroid dehydrogenase 17 hydroxylase 21 hydroxylase 11 hydroxylase
What does ACTH cause?
Cortisol production
Describe the pattern of cortisol secretion?
Diurnal - peaks at around 8:30 in the morning and is lowest around midnight/1am
Describe the pathway from cholesterol to aldosterone
Cholsterol Progesterone 11-deoxycorticosterone corticosterone aldosterone
Describe the pathway of cholesterol to cortisol
Cholesterol Progesterone 17- hydoxyprogesterone 11-deoxycortisol cortisol
Describe the pathway of cholesterol to oestrogen
Cholesterol Progesterone 17-hydroxyprogesterone Sex steroids Androgens Oestrogen
What is Addison’s disease?
Primary adrenal failure
What is the commonest cause of Addison’s in the UK?
Autoimmune
What is the commonest cause of Addison’s worldwide?
TB bacteria destroying the adrenal gland
Why does Addison’s cause tanning?
We get an increase in ACTH due to negative feedback which is a product of POMC breakdown, along with MSH to increase pigmentation
What does POMC break down into?
MSH, ACTH, endorphins, enkephalins, other peptides
Where is POMC synthesised?
In the pituitary
What are the signs of Addison’s?
Skin pigmentation Autoimmune vitiligo Darkening of hair Loss of weight Muscular weakness Hypotension
What are the 3 main causes of adrenocortical failure?
TB Addisons
Autoimmune Addisons
Congenital adrenal hyperplasia
What are the consequences of adrenocortical failure?
Hypotnesion Loss of salt in urine (hyponatremia) Hyperkalemia Hypoglycaemia (glucocorticoid deficiency) Tanning Eventual death due to severe hypotension
What is the normal range for cortisol?
270-290nM
How do we test for Addison’s
Low 9am cortisol
High ACTH
No response after injecting 250µg synACTHen
Why do we not give aldosterone for treatment of adrenal failure?
Half life too short for daily administration
What do we use to treat adrenal failure?
Fludrocortisone 50-100mcg/daily
Why do we use fludrocortisone?
Fluorine doesn’t occur naturally in steroids therefore slows down metabolism and has much longer lasting effects (18h)
Why do we not give oral hydrocortisone?
It ca be given but has too short a half life to be given once daily and can be harmful if given in too high a frequency therefore we opt for alternatives in replacing cortisol
What is another name for 1,2-dehydrocortisone?
Prednisolone
What dose of prednisolone can we give?
1mg, 2,5mg, 5mg once daily
Why is prednisolone absorption slowed?
Not enteric coated
Instead of prednisolone, what can we give alongside fludrocortisone?
We can give hydrocortisone 3 times daily (10, 5, 2.5 mg) to replicate the diurnal pattern of cortisol
What is congenital adrenal hyperplasia?
Missing enzyme
What is the most common enzyme missing?
21-hydroxylase
What do we have in complete 21-h deficiency?
Cortisol and aldosterone deficient
Excess sex steroids (mainly testosterone)
What is the survival rate for complete 21-h deficiency
Less than 24 hours unless given IV saline - as a neonate you are no longer dependent on placenta therefore have an Addisonian salt losing crisis
What may we see in girls with complete 21-h deficiency?
Ambiguous genitalia (virilisation), prompting us to give hydrocortisone - we don’t notice in boys
What do we have in partial 21-h deficiency?
Still deficient in cortisol and aldosterone but there is enough to get by
Still excess sex steroids and testosterone
What is the presentation like in partial 21-h deficiency?
Presentation is much later, with hirsutism in girls and precocious puberty in boys
What do we see in 11-h deficiency?
We should lose aldosterone and cortisol but 11-deoxycorticosteorne behaves just like aldosterone:
No cortisol or aldosterone
Excess 11-deoxycorticosterone, sex steroids and testosterone
What is the presentation of 11-h deficiency?
Virilisation, hypertension and hypokalaemia
What do we see in 17-h deficiency?
Deificient in cortisol and sex steroids
Excess 11-deoxycorticosterone and aldosterone
What is the presentation of 17-h deficiency?
Hypertension Hypokalemia Sex steroid deficiency No puberty (you look like a child) Glucocorticoid deficiency (low glucose)
