adrenal disorders Flashcards
clinical features of Cushing’s *
too much cortisol centripedal obesity, thin arms and legs - cortisol ioncreasses hunger and fat production but make less protein
moon face
buffalo hump
proximal myopathy - weak because cortisol stops the production of proteim
hypertension and hypokalaemia
thin skin and bruising - ecchymosis poor wound healing
osteoporosis
T2DM - increased glucocorticoids increase glucose so have impaired glucose tolerance
red cheeks
peripheral oedema - pitting
acne - androgens are stimulated
depression
purple striae
loss of libido if adrenal making tumour
causes of Cushing’s syndrome *
taking too many catabolic steroids eg glucocorticoids (cortisol or prednisolone)
pituitary dependant cushings disease- corticotroph adenoma makes ACTH
ectopic ACTH from lung cancer
adrenal tumour just amking cortisol
investigations to determine the cause of cushing’s syndrome *
24hr urine collection for urinary free cortisol, If too high it would suggest cushing’s - it is the wake up hormone, higher in the morning blood diurnal cortisol levels - cortisol normally highest at 9am and lowest at midnight if asleep - if you have cushings, lose the diurnal rhythm so always high - can only see this loss of rhythm when cortisol is meant to be low
low dose dexamethasone suppression test - last long time, v potent steroid -give 0.5mg 6 hourly for 48hrs normally this would supress ACTH and so cortisol production if it doesn’t get supressed to 0= cushings
dexamethasone suppression test - give at 11pm - cortisol should be low in the morning, if it isnt suppressed = cushings
midnight cortisol - diurnal rhythm lost of cortisol high at mignight = cushings
how would you diagnose cushing’s *
basal cortisol (9am) = 800nM end of low dose dexamethasone suppression test - 680nM
state the 2 mechanisms for treatment of Cushing’s *
enzyme inhibitors
receptor blocking drugs
what are the inhibitors of steroid biosynthesis used to treat Cushing’s disease *
metyrapone
ketoconazole
what is the principle of treatment for Cushing’s *
definitive treatment will be surgery
what is the principle of treatment for Cushing’s *
definitive treatment will be surgery however skin is v friable, and there is a lot of bleeding cortisol supress immune system so can cause infection therefore want medical treatment to prepare for surgery treatment depends on the cause - pit surgery (transsphenoidal hypophysecotomy) for cushing’s DISEASE bilateral adrenalectomy in you have ectopic ACTH unilateral adrenalectomy for adrenal mass
describe the mechanism of action of metyrapone *
inhibition on 11b-hydroxylase which is the enzyme in the final step of the production of cortisol and corticosterone through -ve feedback this means ACTH secretion increases and 11-deoxycortisol in the plasma increases - low cortisol means it is not inhibited because the precursors for cortisol will have increased- more sex hormone is produced as all the precursors go down this pathway - means there is increased androgen production = hirsutism in women (unwanted effect) also precursor for corticosterone, 11-deoxycorticosterone, levels are increased - this acts like aldosterone - increased Na and so water retention and K excretion = hypertension
unwanted effects of metyrapone *
hypertension hirsutism Nausea, vomiting, Sedation Hypoadrenalism
describe uses of metyrapone *
control of Cushing’s prior to surgery - adjust dose according to cortisol - aim for mean serum cortisol 150-300nmol/L improves patient symptoms and promotes post-op recovery - better wound healing, less infection etc control after radiotherapy - usually slow acting given orally
describe ketoconazole mechanism of action *
issue is it causes hepatotoxicity - cause death at high conc inhibits steroidogenesis used in prep for surgery orally active block production of glucocorticoids, mineralocorticoids and sex steroids by inhibiting 17a-hydroxylase
unwanted effects of ketoconazole *
liver damage possible fatal so monitor liver function weekly, clinically and biochemically nausea vomiting reduced androgen production
clinical features of Conn’s *
aldosterone in excess therefore hypertension and hypokalaemia
oedema
diagnosis of Conn’s *
measure the hormones if aldosterone is high and renin is low (because of -ve feedback of the renin-angiotensin system)it is Conns measure renin to rule out secondary hyperaldosteronism (renin would be high)
what type of drug is used to treat Conn’s and give 2 examples *
MR antagonist spironolactone and epleronone they block the way the hormone can work
describe the mechanism of action for spironolactone *
it is a prodrug converted to canrenone - a competitive antagonist of MR this blocks Na resorption and K excreting - treat the hypokalaemia - K sparing diuretic it is orally active, metabolised in the liver and largely protein bound
unwanted actions of spironolactone *
menstrual irregularities - they stimulate the progesterone receptor because they are not specific to MR gynaecomastia inhibit the androgen receptor - this is difficult for men to tolerate GI tract disturbance blood dyscrasias - more than one blood component gets impaired
describe epleronone *
MR antagonist similar affinity to spironolactone however binds less to androgen and progesterone receptors so is better tolerated
what are phaeochromocytomas *
tumours of the adrenal medulla which secretes catecholamines ie adrenaline or NA
clinical features of phaeochromocytomas *
they suddenly secrete loads of A or NA, which binds to a and b receptors cause sudden SNS response headache sweating sudden anxiety vomiting palpitation weakness dizziness pallor dyspnoea increased CO substernal pain hypertension in young people episodic severe hypertension (possibly after abdo examination, because poked tumour and caused A release) common in certain inherited conditions - dominant in all
risk of a phaeochromocytoma *
can be fatal causing a stroke or heart attack because of severe hypertension high adrenaline can cause vfib and death
describe the management of phaeo *
eventually need surgery need prep though because anaesthetic can cause a hypertensive crisis alpha blockade is the 1st step - patients need IV fluid at same time otherwise sudden drop may cause severe hypotension beta blockade to prevent tachycardia with this medical therapy the patient is safe to wait for surgery
key facts about phaeo *
10% extra-adrenal ie in sympathetic chain 10% malignant 10% bilateral rare
cause of conn’s *
benign adrenal cortical tumour in the zona glomerulosa secreting aldosterone
describe surgical treatment of Conn’s *
laparoscopic adrenalectomy when you have unilateral adrenal adenoma
describe medical treatment of Conn’s *
usually chosen for bilateral disease eg bilateral adrenal hyperplasia
parts of the cortex from outside in and the hormones they make
tough, fibrous capsule
zona glomerulosa - aldosterone (mineralocorticoids)
zona fasciculata and zona reticularis - cortisol (glucocorticoids)
cortex also make sex steroids - androgens and oestrogens
what hormones does the medulla make
catecholamines - adrenaline, noradrenaline
what increases renin production
low Na conc
renal perfusion pressure decrease
increase in renal sympathetic activity
where is renin produced
granular cells of the kidney
describe how the renin-angiotensin system is linked to aldosterone secretion
macular densa cells sense Na drop in fluid in kidney
stimulates renin production
Increases Na reabsorbtion and so water - maintains Bp (low Bp shown by low RPP)
renin is enzyme number 1, activates angiotensinogen to angiotensin 1
lung have a lot of angiotensin converting enzyme (ACE) – angiotensin II
stimulates production of aldosterone in adrenalcortico gland which causes Na and so H20 retention
other stim for aldosterone synth
-increased K+
decreased Na+
describe the physiological effect of aldosterone
act in kidney
late distal tubule/collecting duct
Na is driven into DCT then into the blood
Na channel at lumen - Na enters by diffusion if concentration gradient
Na/K ATPase makes sure there is a conc gradient as Na is removed into the blood
some K is lost
aldosterone is slow acting, it increases the number of Na channels and ATPases ie it upregulates the ability to absorb Na
allows water to diffuse through DCT as it provides an osmotic gradient
what is the disease with adrenal failure
addison’s
what is teh ACTH precurser
pro-opio-melanocortin (POMC)
why are people with high ACTH tanned
also have high levels of MSH
what is POMC cleaved into
ACTH
MSH
endorphins
describe Addison’s
primary adrenal failure
autoimmune disease - wipe out cortex (main cause in UK)
TB main cause worldwide- spreads from lungs
signs of Addison’s
increased pigmentation in mouth and scars
low na
low bp - no cortisol/aldosterone
not retaining Na
autoimmune disease that coexists with Addison’s
vitiligo - immune system take out cells
replace by patches with no colour
symptoms of addisons
extreme fatigue
vomiting
weight loss
dizziness on standing - postural hypotension
tanned
hyponatraemia
hyperkalaemia
do you need exogenous steroids when one of the adrenal glands has been removed?
no still have another
however the excess cortisol might have shut down the other adrenal, so need to do a short synacthen test to see if you need to give steroids
What is an Addisonian crisis *
when addison’s disease is left untreated, the adrenal hormones get really low until you go into addisonian crisis
what are the signs of addisonian crisis *
severe dehydration
pale, cold, clammy skin
sweating
rapid, shallow breathing
dizziness
severe vomiting and diarrhoea
severe muscle weakness
headache
severe drowsiness or loss of consciousness
