6. Hyperadrenal disorders Flashcards
what is cushing’s a result of?
too much cortisol
what are the clinical signs of cushing’s syndrome?
- thin skin
- proximal myopathy
- centripetal obesity (lemon on sticks)
- diabetes, hypertension and osteoporosis
- immunosuppression
- moon face
- red striae and bruising
what is the difference between cushing’s syndrome and cushing’s disease?
cushing’s syndrome is a collection of symptoms which could have any cause
cushing’s disease is when the cause is known to be a pituitary adenoma
what drug’s side effects are the same as the symptoms of cushing’s disease?
steroids
what can cause cushing’s?
- too many steroids
- pituitary dependent cushing’s disease
- ectopic ACTH from lung cancer
- adrenal adenoma secreting cortisol
why is measuring blood cortisol not very reliable?
the amount of blood cortisol in a patient changes with time of day - cortisol is usually highest at 9am and lowest at midnight if asleep
how can you determine the cause of cushing’s syndrome?
24h urine collection for urinary free cortisol - high level suggests cushing’s
what happens to the diurnal rhythm of cortisol if you have cushing’s?
the diurnal rhythm is lost because you have a tumour in the pituitary or adrenal gland that is pushing out cortisol all the time at a fixed rate
what does a midnight sleeping cortisol test show?
if midnight cortisol is low, cushing’s isn’t present
how is cushing’s diagnosed?
- basal cortisol of 800nM at 9am
- cortisol level of 680nM at the end of Low Dose Dexamethasone Suppression Test
what is a Low Dose Dexamethasone Suppression Test (LDDST)?
dexamethasone is a potent artificial analogue of cortisol (artificial steroid). the pituitary detects the drug and stops making ACTH (and so cortisol). normal patients will suppress their cortisol levels to 0, any cause of cushing’s will fail to suppress with low dose dexamethsone
what is the dosage given in an LDDST?
0.5mg every 6hrs for 48hrs
what are the treatment options for cushing’s?
- enzyme inhibitors of enzymes involved in cortisol production
- receptor blocking drugs
- surgery
how may a pituitary adenoma and adrenal tumour be treated?
pituitary adenoma - pituitary surgery (transsphenoidal hypophysectomy)
adrenal tumour - bilateral adrenalectomy
what drugs are used to treat cushing’s?
- metyrapone
- ketoconazole
how does metyrapone treat cushing’s?
metyrapone stops the adrenal cortex from making cortisol by inhibiting the enzyme 11b-hydroxylase
steroid synthesis stops at the 11-deoxycortisol stage and the level of this steroid increases
what indirect effects occur as a result of inhibiting 11b-hydroxylase?
cortisol has a negative feedback on ACTH but 11-deoxycortisol has no negative feedback effect on the hypothalamus or pituitary so you get an increase if ACTH and accumulation of deoxycortisol in the plasma
there is also less corticosterone production as the enzyme to produce corticosterone is also 11b-hydroxylase
why might metyrapone be used prior to surgery?
improves the chance of post-op recovery and controls the symptoms of cushing’s after radiotherapy (slow to take effect)
oral dose is adjusted according to cortisol to reduce cortisol levels and improve patient symptoms
what is the effect of inhibition of 11b-hydroxylase preventing corticosterone production?
its precursor 11-deoxycorticosterone builds up and has a mineralcorticoid effect resulting in increased Na reabsorption (and so water), hypertension and increased K excretion
what unwanted action can metyrapone have on females?
hursutism (abnormal hair growth) due to increased adrenal androgen production
how does ketoconazole treat cushing’s?
it blocks the production of glucocorticoids, mineralocorticoids and sex steroids as it blocks the steroid synthesis pathway at the start
what are the uses of ketoconazole?
treatment and control of symptoms prior to surgery
drug is orally active
what are the unwanted actions of ketoconazole?
liver damage which is possibly fatal - liver function must be monitored weekly (clinically and biochemically)
what is conn’s syndrome?
benign adrenal cortical tumour in the zona glomerulosa resulting in XS aldosterone production
what does conn’s syndrome result in?
retention of sodium and excretion of potassium which results in hypertension and hypokalaemia
how is conn’s syndrome diagnosed?
primary hyperaldosteronism
renin-angiotensin system will be suppressed due to high BP
diagnostic test = high aldosterone, low renin
how is conn’s syndrome treated?
- spironolactone - aldosterone receptor antagonist
- epleronone - better tolerated aldosterone receptor antagonist
- surgery - image and remove adenoma
what is the mechanism of action of spironolactone?
spironolactone is converted into several active metabolites including canrenone, which is a competitive antagonist of the mineralocorticoid receptor. it blocks Na+ reabsorption and K+ excretion in the kidney tubules (potassium sparing diuretic)
where is spironolactone metabolised?
in the liver
what are the unwanted actions of spironolactone?
menstrual irregularities (it is a progesterone receptor agonist) and painful gynaecomastia (it is an androgen receptor antagonist)
why is epleronone the drug of choice as opposed to spironolactone?
has a similar affinity to the mineralocorticoid receptor as spironolactone but there’s less binding to androgen and progesterone receptors so it is better tolerated
what are phaeochromocytomas?
tumours of the adrenal medulla that secrete catecholamines (adrenaline and NA) which lead to high BP, increased CO, increased BMR, airway dilation
what can phaeochromocytomas result in and why?
stroke, MI
the tumour degranulates and releases a lot of adrenaline so BP increases quickly - results in severe anxiety, panic, vasoconstriction but only short lasting
what are the clinical features of phaeochromocytomas?
- hypertension in young people
- sudden rise in adrenaline
- episodic severe hypertension after abdominal palpitation
- ventricular fibrillation
what is the primary treatment of phaeochromocytomas?
surgical removal of adrenal tumour
what is done to prevent a hypertensive crisis in a patient undergoing surgery for a phaeochromocytoma?
- alpha blockade - blocking adrenoreceptors causes decreased BP
- IV fluid - to prevent a drastic fall in BP
- beta blockade- to prevent tachycardia
what % of phaeochromocytomas tend to be malignant?
10%
