Adrenal disorders 2 Flashcards
Why may someones cortisol be high at midnight and not have hypoadrenalism?
Sleep schedule e.g. night shifts or time zones
What are the clinical features of cushings’?
Overactive adrenal gland due to increased ACTH :
- Too much cortisol
- Centripetal Obesity
- Moon face and buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red Striae, thin skin bruising
- Osteoporosis
What are the common causes of Cushings’?
–> Taking too many steroids!
- Pituitary dependent Cushings’ disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
CUSHINGS IS SECONDARY HYPERCORTISOLISM
How to investigate the cause of Cushing’s syndrome?
- 24h urine collection ( for urinary free cortisol ) *total cortisol not affected by time
- Blood diurnal cortisol levels *dependent on time of day so highest at 9am
What is the low dose dexamethasone suppression test? ( a steroid )
Also a test of cushings’ syndrome cause
potent
pituitary sees it and reacts to it as if it is cortisol so will make no ATCH. Cortisol should be 0 however Cushings will still remain high
How much dexamethasone is given for the test?
0.5mg 6 hourly for 48 hours
How do we know to diagnose Cushings?
If 9am cortisol is 800nM and suppression test is given and it only drops to 680nM (due to diurnal) then this is Cushings’
Is anyone else it should drop to 0
What is pitting eodema?
If high aldoesterol or cortisol : have it
What are the pharmacological treatments?
- Enzyme inhibitors
- Receptor blocking drugs
to control excess cortisol
What drug is used to inhibit tsteroid biosynthesis?
Metryapone + ketoconazole
What is Conn’s syndrome?
Benign adrenal cortical tumour - zona glomerulosa
Excess aldoesterone
What medication is given for Conn’s?
MR antgonist:
spironolactone, epleronone
How does Metryapone work?
Inhibition of 11beta-hydroxlase in zona fasciuclata which drops level of cortisol
So reaction ends at 11-deoxycortisol
How do we control Cushing’s syndromes before surgery?
- adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc)
- can give metyrapone whilst waiting for for radiotherapy to work
What are the side effects of metyrapone?
Hypertension on long term administration
Hirsutism
How does Ketoconazole work?
main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
Blocks 17alpha hyrdroxylase
What are the side effects of ketoconazole?
Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically
What surgeries are available for Cushing’s?
( Depends on cause )
- Pituitary surgery - transsphenoidal hypophysectomy
- Bilateral adrenalectomy
- Unilateral adrenalectomy for adrenal mass
What are the symptoms of Conn’s syndrome?
Hypertension + hypokalaemia
How to diagnose Conn’s syndrome?
Primary hyperalodosteronism
Renin : angiotensin system should be suppressed if this is the case to exclude secondary hyperalodosteronism
How does Spironlactone work?
For Conns
Converted to sevreal metbabolites includng canrenone acting as a copetitive antagonist of the mineralcorticoid receptor
Blocks Na+ resorption and K+ excretion
- it is orally taken and is very protein bound
What side effects does spironolactone cause?
Menstrual irregularities (+ progesterone receptor) Gynaecomastia (- androgen receptor)
How does Epleronone does?
Mineralcorticoid receptor antagonist
Similar affinity for MR compared to spionolactone
Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated
What are phaemochyromocytomas?
These are tumours of the adrenal MEDULLA which secrete catecholamines
ADRENALINE and noadrenaline made
What are the clinical features of phaeochromocytoma?
- Hypertension in young people
- Episodic severe hypertension when adrenaline builds and is released ( due to neural cell type effect ) after abdominal palpation
More common in certain inherited condition
What can the severe hypertension in Phaeo cause?
Can cause myocardial infarction strokes
High adrenaline can cause ventricular fibrillation + death
MEDICAL EMERGENCY
How to manage Phaeo?
Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis
What are the therapuetic management plans for Phaeo?
- alpha blockade is first therapuetic step
- May need IVF fluid as alpha blockade causes blood pressure crash
- Beta blockade added to prevent tachycardia
