hyperadrenal disorders Flashcards
What are the clinical features of Cushing’s?
Too much cortisol.
Centripetal obesity.
Moon face + buffalo lump
proximal myopathy.
Hypertension and hypokalaemia.
red striae, thin skin and bruising.
Osteoporosis, diabetes.
What can cause Cushing’s syndrome?
Taking too many steroids.
Pituitary dependent Cushing’s disease.
Ectopic ACTH from lung cancer.
Adrenal adenoma secreting cortisol.
What investigations can be done to determine cause of Cushing’s syndrome?
24hr urine collection for urinary free cortisol.
Blood diurnal cortisol levels.
(cortisol usually highest at 9am, lowest at midnight if asleep).
Low dose dexamethasone suppression test.
What effect does Cushings have of the diurnal rhythm of cortisol?
Cortisol is always high and doesn’t fluctuate according to time of day or sleeping/waking.
How does the dexamethasone suppression test work?
0.5mg 6 hourly for 48 hours.
Normal person will have no cortisol afterwards.
Any form of Cushing’s will fail to suppress.
How might Cushing’s be treated?
Enzyme inhibitors.
Receptor blocking drugs.
Pituitary surgery.
Bilateral adrenalectomy.
Unilateral adrenalectomy for adrenal mass.
Name two important inhibitors of cortisol synthesis.
metyrapone, ketoconazole.
outline the mechanism of action of metyrapone.
Inhibition of 11 beta-hydroxylase.
steroid synthesis in zona fasciculata arrested at 11-deoxycortisol stage.
What are the effects of metyrapone administration?
Cortisol and corticosterone synthesis blocked.
ACTH secretion increased.
Plasma 11 deoxycortisol increased.
How is Cushing’s syndrome controlled before surgery?
Adjust dose of metyrapone acccording to cortisol levels (aiming for 150-300nmol/L) - improve patient’s symptoms and promote better post-op recovery.
Why is metryapone used after radiotherapy?
Control symptoms of Cushing’s syndrome till radiotherapy takes effect.
What are the effects of high 11-deoxycorticosterone as a result of blocked corticosterone synthesis due to metryapone?
Accumulation in z. glomerulosa. Aldosterone like activity –> Salt retention and hypertension.
What other effect might metyrapone have?
Increased adrenal androgen production in women.
What are the unwanted actions of metyrapone?
Hypertension with long term administration.
Hirsutism.
What are the main uses of ketoconazole?
Mainly antifungal agent.
At high concentrations inhibits steroidogenesis of cortisol.
What is the mechanism of action of ketoconazole?
Inhibit cytochrome P450 - inhibit synthesis of aldosterone, corticosterone, cortisol, androgens.
What are the uses of ketoconazole?
Treatment and control of symptoms of Cushing’s prior to surgery.
What are the unwanted actions of ketoconazole?
Liver damage.
What is Conn’s syndrome?
Excess aldosterone.
Benign adrenal cortical tumour.
Hypertension ans hypokalaemia.
How is Conn’s syndrome diagnosed?
Blood test - high aldosterone, low renin.
How is Conn’s syndrome treated with drugs?
Blocking of aldosterone receptor.
e.g. spironolactone, epleronone.
What is the mechanism of action of spironolactone?
Converted to several active metabolitesm, e.g. canrenone - a competitve antagonist to mineralocorticoid receptor.
Blocks Na+ resorption and K+ excretion in kidney tubules.
What are the unwanted actions of spironolactone?
Why?
Menstrual irregularities (progesterone receptor agonist)
Gynaecomastia (androgen receptor antagonist)
Not specific for mineralocorticosteroid receptor.
How is epleronone different to spironolactone?
Less binding to androgen and progresterone receptors.
What are phaeochromocytomas?
Tumours of adrenal medulla which secretes catecholamines - secrete NA and A
What are the clinical features of a phaeo?
Hypertension in young people - can cause MI or stroke.
episodic severe hypertension (after abdominal palpation).
More common in certain inherited conditions.
What is a potential complication of high adrenaline?
ventricular fibrillation + death.
How is phaeo managed?
Surgery needed, but careful anaesthetic preparation due to potential hypertensive crisis - block effects of adrenaline.
How can the effects of adrenaline be blocked prior to phaeo surgery?
Alpha blockade is first therapeutic step.
Patients may need IV fluid as alpha blockade commences.
Beta blockades added to prevent tachycardia.
What % of phaeos are extra-adrenal, malignant, bilateral?
10%
