Endo - Adrenal Disorders 2 Flashcards
Describe the rhythm of cortisol?
Diurnal rhythm
What is a the concentration of cortisol at its peak
428nM
What is the concentration of cortisol at its lowest
55nM
When should we check if cortisol is too low
We should check it in the morning when it is meant to be highest ie 9am
What may affect cortisol rhythm
Nightshift workers or people with altered body clock will have e different times as to when cortisol peaks
What are the symptoms of Cushing’s?
Centripetal obesity Moon face Purple striae Proximal myopathy Buffalo dumb between shoulders Hypertension Hypokalaemia Thin skin Bruising Diabetes Osteoporosis Pitting oedema
What are the causes of Cushings
Steroid use
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma
What are the steps to investigating Cushings
Establish a source for potential Cushings
24 hour urine collection for urinary free cortisol
Blood diurnal cortisol levels - measured at different times over the day/night
Outline a LDDST
Low dose dexamethasone suppression test - this is a glucocorticoid with fluoride therefore we give 0.5mg every 6 hours for 48 hours to see if cortisol production is suppressed due to negative feedback (ACTH should go down) - If cortisol doesn’t go to 0 then there is Cushings
What do we need to know before we start treating Cushings
We need to know where the source of Cushings is
What must be done before an operation for Cushings
We must reduce cortisol via pharmacological manipulation of steroids
What are examples of enzyme inhibitors?
Metyrapone
Ketoconcazole
What are examples of receptor blockers
Spironolactone Epleronone (Both block aldosterone receptors)
How does metyrapone work?
Blocks 11-Beta-Hydroxylase therefore blocks the conversion of 11-deoxycortisol to cortisol. There is no negative feedback therefore this works well.
How do we adjust dosage of metyrapone?
Aim for a serum cortisol of 150-300nmol/L
When is metyrapone used?
Used after radiotherapy for Cushings
What are the side effects of metyrapone?
We get increased adrenal androgen production therefore hirsutism in women.
We also get a build up of 11-dexoycorticosterone as it cannot be converted to aldosterone therefore we get hypertension (however, some 11-deoxycorticosterone is converted to aldosterone via aldosynthase)
How does ketoconazole work?
Antifungal drug that blocks 17-alpha-hydroxyalse therefore inhibiting cortisol production
What is a possible side effect of ketoconazole?
Risk of hepatotoxicity as it is an antifungal - at a higher concentration it inhibits steroidogenesis
What surgery can be used for Cushings disease from the pituitary?
Transphenoidal hypophysectomy
What Cushings surgery may we use if there is ectopic ACTH from lung cancer?
Bilateral adrenalectomy
What surgery can be used for a one sided adrenal mass?
Unilateral adrenalectomy
Is surgery preferred over drugs?
Yes
What is Conn’s syndrome?
Benign tumour of the glomerulus therefore we get unregulated production of aldosterone
What should we do if we ever find a high blood pressure?
Check if they have hypokalaemia - Conn’s syndrome increases aldosterone which in turn increases blood pressure but excretes potassium
Describe the RAAS in Conn’s
Suppressed - aldosterone is high despite renin being low, this typically indicates Conn’s
How do we treat a Conn’s adenoma?
Remove it
What drugs should we use for Conn’s before a surgery
use a drug that blocks aldosterone recpetors
How does Spironolactone work?
Mineralocorticoid receptor antagonist, after being converted into canrenone to stop Na reabsorption or K excretion in the tubules.
It is orally active and highly protein bound, and metabolised in the liver
What are the side effects of spironolactone?
Menstrual irregularities (as it can stimulated the progesterone receptor) Gynaecomastia (as it blocks androgen receptor)
How does epleronone work?
MR antagonist with a similar affinity to spironolactone
Describe the side effects of epleronone
It binds less to other steroid receptors therefore has less side effects compared to spironolactone
What is a phaeochromocytoma?
This is an adrenal medulla tumour therefore we get an increase in the production of catecholamines (noradrenaline and adrenalin)
Why can phaeos cause a heart attack or stroke?
The tumour of the medulla acts as a neural syncytium therefore builds up adrenaline and doesn’t release it until a certain moment and at this point, it releases a great quantity of adrenalin to cause this heart attack or stroke via random cell degranulation
What are the clinical features of a phaeo?
Hypertension in young people
Episodic severe hypetension (often triggered e.g. if you poke the abdomen)
Cna cause sudden MI or CVA therefore death
What are the 2 stages if phaeo management?
Stabilise patient
Surgery
What drugs do we first give to a phaeo patient?
Alpha blockade to block alpha adrenoreceptors - this causes a fall in blood pressure
Why may we get low blood pressure in a phaeo patient and how do we stop this?
Because patients are used to high adrenaline therefore a fall in adrenaline means their blood pressure drops too low, as they are resistant to lower levels of adrenaline.
We. can treat this by giving IV fluids with blockade
How do we prevent tachycardia in a phaeo patient?
Beta blockade (Beta blockers)
What is the rule of 10 for phaeos?
10% are extra adrenal in the sympathetic chain
10% are malignant
10% are bilateral
Can phaeos run in the family?
Yes - there are a few genes which put you at risk, and phaeos are more common in certain inherited conditions
