Hyperadrenal disorders Flashcards
What is the main problem in Cushing’s
Too much cortisol
What can too much cortisol caused by?
Taking too many steroids
Pituitary dependent–> Cushing’s disease not syndrome
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol
What does cortisol do?
Switches protein synthesis off and fat synthesis on
What is Cushings DISEASE caused by?
Tumour of the pituitary
What are the clinical features of Cushings?
Too much cortisol -Increase fat and reduce protein Centripetal obesity Buffalo hump and moon face Proximal myopathy Hypertension and hypokalaemia Red striae, thin skin and easy bruising Osteoporosis, diabetes
What are the causes of Cushing’s syndrome?
Taking too many oral steroids (cortisol like steroids- glucocorticoids)
Ectopic ACTH from lung cancer
Adrenal adenoma
What is the first thing you do if you see a patient presenting with all the symptoms of cushings?
Measure their cortisol
24 hr urine collection for urinary free cortisol
What is the problem with measuring cortisol?
Dependent on diurnal rhythm
It varies throughout the day- it is high in the morning and low in the evening (midnight it is very low)
Also pain and stress of blood test will increase cortisol
What would you see if someone has Cushing’s and you measure their cortisol at midnight?
It wouldn’t be low
What is another test to see if someone has Cushing’s?
Use the negative feedback system- if you gave a normal person low dose dexamethasone your pituitary will detect extra steroid and it will turn off the ACTH and within hours you will have zero cortisol
What are the three tests you can do to identify the cause of Cushings?
24 hour urine collection for urinary free cortisol
Blood diurnal cortisol levels
Low dose dexamethasone suppression test (Gold standard)
What is the treatment of Cushing’s syndrome?
Depends on cause
Pituitary surgery (transphenoidal hypophysectomy)
Bilateral adrenalectomy- can’t make anymore cortisol
Unilateral adrenalectomy for adrenal mass
What is the main problem in Conn’s?
What might this be due to
Present with
Too much aldosterone
Benign adrenal cortical tumour– zona glomerulosa
Hypertension and hypokalaemia
Where are catecholamines produced?
Adrenal medulla
What is a tumour of the adrenal medulla that leads to lots of catecholamines called?
What happens as a result of the catecholamines
Phaeochromocytoma
Sudden release of catecholamines– bind to alpha and beta receptors
- increased b.p, vasoconstrict
Stroke,heart attack
What is the first step to block the effects of the excess catecholamines?
Give an alpha blocker
Why do you give an alpha blocker first when treating phaeochromocytoma?
The urgent issue is really high blood pressure caused by catecholamines binding to alpha receptors in vasculature leading to vasoconstriction
What do you give once the blood pressure has decreased when treating phaeochromocytoma?
Other treatment
Beta blocker
surgery- but patients require careful preparation as anaesthetic can precipitate a hypertensive crisis
Different parts of of the adrenal gland
Which part produces
Cortisol
Aldosterone
Oestrodiol
HYPERADRENAL DISORDER TREATMENT
Drugs that inhibit steroid biosynthesis
MR antagonist:
Cortex -Glomerusa zona -Fasciculata -Reticularis Medulla
Cortisol produced by Zona Fasciculata-FC
Aldosterone produced by Zona Glomerula- GA
Oestrodiol produced by Zona reticularis- OR
11beta-hydroxylase
Drugs that inhibit steroid biosynthesis:
Metyrapone; ketoconazole
MR antagonist:
Spironolactone, epleronone
Drug that inhibits 11 beta-hydroxylase
What does inhibiting 11beta-hydroxylase do?
-Metyrapone
Slows down the cortisol synthesis pathway by inhibiting the conversion of 11-deoxycorticosterone to corticosterone and conversion of 11-deoxycortisol to cortisol so it decreases levels of corticosterone and cortisol
What happens due to arrest at 11- deoxycortisol stage
What happens due to the decrease in cortisol when using metyrapone?
Nothing 11- deoxycortisol has no negative feedback to hypothalamus
The levels of ACTH rise
Plasma deoxycortisol increased
When is metyrapone used for Cushing’s patients? (2)
Prior to surgery- Cushings patients are not good surgical candidates as predisposed to infection and do not heal easily (thin skin)
After radiotherapy- effects of radiotherapy are slow to be seen so metyrapone is used till then
taken orally
What are the two negative things about metyrapone?
Leads to accumulation of 11-deoxycorticosterone and 11-deoxycortisol- 11-deoxycorticosterone has mineralocorticoid properties, it leads to retention of sodium and excretion of potassium in the kidneys so you get salt retention and hypertension
Second problem- Because two limbs of pathway are blocked, all the precursors are funnelled towards sex steroid synthesis so there is an increase in adrenal androgens which can cause hirsuitism and is particularly unpleasant in women
What are the unwanted aspects of metyrapone?
Hypertension
Hirsutism
What is the main use of ketoconazole?
Anti-fungal (withdrawn in 2013 due to high risk of hepatotoxicity)
What else can ketoconazole be used for?
Inhibit cortisol production at high doses
How does ketoconazole inhibit cortisol production?
Mainly blocks 17 alpha hydroxylase inhibiting cortisol production
When is ketoconazole used?
In a similar way to metyrapone, before surgery
taken orally
What are unwanted actions of ketoconazole?
Liver damage
What is the cause of Conn’s syndrome?
Benign adrenocortical tumour– zona golmerulosa
Where is aldosterone made?
Zona glomerulosa
What does excess aldosterone in Conns cause?
Sodium retention and potassium loss- hypertension and hypokalaemia
How is Conns treated?
To stop effects of excess aldosterone you give a mineralocorticoid receptor antagonist such as spironolactone
Surgery - image and remove tumour
What are the side effects of spironolactone?
Spironolactone MOA
It is very non-specific so there are lots:
Menstrual irregularities (progesterone receptor antagonist)
Gynaecomastia in men (androgen receptor antagonist)
Blocks Na+ resorption and K+ excretion in the kidney tubules- potassium sparing diuretic
-Spironolactone is a prodrug
converted into several metabolites e.g canerenone a competitive antagonist of the MR
What is eplerenone?
Mineralocorticoid receptor antagonist
Why eplerenone used more frequently than spironolactone?
Less side effects (more specific)
What is the main effect of a phaeochromocytoma?
Large release of adrenaline will cause a large increase in blood pressure which could lead to a stroke. There is a sudden onset of pain, fever, tachycardia and hypertension
When would you especially expect phaechromocytoma?
Episodic severe hypertension in young people
How do you manage a phaeochromocytoma?
Eventually they need surgery but patient has to be very carefully prepared for surgery as anaesthetic can precipitate a hypertensive crisis
How do you prepare a patient with phaeochromocytoma for surgery?
First you give a drug to block the receptor to which adrenaline binds- alpha blocker (patients may need IV fluid as this commences)
Once you’ve done this you give them a beta blocker to prevent tachycardia
What percentage of phaeochromocytomas are outside the adrenals?
10%
What percentage of phaeochromocytomas are malignant?
10%
What percentage of adrenals are affected bilaterally
10%
