cushings syndrome Flashcards
defintion
clinical abnormalities which arise due to any state of prolonged excess cortisol
cushings disease
refers specifically to a pituitary adenoma which is secreting ACTH and is a cause of cushings syndrome
causes of cushings syndrome
divided into endogenous causes and exogenous causes
endogenous causes
- pituitary adenoma secreting ACTH (cushings disease)
- tumours of the adrenal gland (adrenal adenomas, adrenal carcinomas)
- ectopic ACTH production (usually small cell lung cancer)
exogenous causes
steroid medication/abuse (oral, topical, IV, inhaled)
the hypothalamus
secretes corticotrophin releasing hormone (CRH) this stimulates the anterior pituitary to secrete adrenocorticoptrohic hormone (ACTH) this travels to the adrenal gland and targets the cells of the adrenal cortex
the adrenal cortex is made up of 3 layers
- zona glomerulosa
- zona fasciculata
- zona reticularis
ACTH specifically
stimulates the cells of the zona fasciculata to secrete cortisol
cortisol belong to a family called
glucocorticoids which are lipophilic and hydrophobic, so 95% of cortisol travels in the blood bound to cortisol binding globulin, only the 5% of free cortisol is active
the levels of free cortisol are
tightly controlled and if there is any excess it is secreted in the urine
in times of stress the hypothalamus
secretes more CRH which in turn increases the amount of free cortisol in the blood
free cortisol does many things
- increases gluconeogenesis, proteolysis and lipolysis
- increases sensitivity of peripheral blood vessels to catecholamines (adrenaline and noradrenaline) which maintains blood pressure
- dampens the immune and inflammatory response by reducing the production and secretion of inflammatory mediators (prostaglandins and interleukins) and reduces the proliferation of T lymphocytes
cortisol works via a
circadian rhythm so for all its action to work properly the level of cortisol in the blood must be maintained within normal limits, except in times of stress where it is helpful to have increased amounts of cortisol
how are normal levels of cortisol achieved
via negative feedback, so when cortisol levels are high the hypothalamus reduces its secretion of CRH and the anterior pituitary reduces its secreting of ACTH
BUT in sucking syndrome
the levels of cortisol in the blood is constantly high so the normal helpful stress response of cortisol become damaging and lead to all the signs and symptoms of cushings syndrome
proteolysis causes
- muscle breakdown causing myopathy (particularly proximal myopathy)
- bone breakdown using osteoporosis
- skin breakdown causing thinning of the skin, striae, and easy bruising
gluconeogensis causes
hyperglycaemia which increases the amount of insulin production, insulin preferential targets adipocytes in the centre of the body where it activate LIPOPROTEIN LIPASE, increasing the uptake of fat molecules into adipocytes causing central obesity
cushings syndrome causes hypertension by
increasing the sensitivity of peripheral blood vessels to catecholamines and also cross reacts with mineralocorticoid receptors triggering mineralocroticoiid affects which is to increase the blood pressure by retaining fluid
other characteristic features cause by excess adipose tissue
moon face, buffalo hump, supracalvicular fat pad
other features of cushings
acne, amenorrhoea, hyperhydrosis, depression, increased susceptibility to infection, frontal balding in woman and depression
initial test when you suspect cushings syndrome
screening tests;
overnight 1mg dexamethasone suppression test: measure cortisol levels in the morning
<50= normal
>100= abnormal
free cortisol in the urine (24hr urine collection)
< 250= normal
>250= abnormal
definitive test
low dose dexamethasone suppression test:
persone is given 2mg/day of dexamethasone for 2 days and 6 hours after the last dose cortisol is measures
<50= normal AND CUSHINGS IS RULED OUT
>100= abnormal and CUSHINGS IS CONFIRMED
what could give you a false positive on dexamethasone suppression test
- anti-epileptic drugs (Phenytoin, carbamepazine), rifampicin, eating disorders, depression, alcoholics with drawing
- in these cases a 24 hour urine cortisol test is preferred
once you have confirmed the diagnosis of cushings syndrome
move onto a high dose dexamethasone test to determine whether the cushings syndrome is caused by a pituitary adenoma secreting ACTH
high dose dexamethasone suppression test
- if the person has a pituitary adenoma causing cushings syndrome there cortisol levels will fall by at least 50% in response to the high dose dexamethasone suppression test
if high dose dexamethasone test causes no change in cortisol levels the person has either a
- Ectopic production of ACTH (most likely a small cell lung carcinoma) OR
- A neoplasia of the adrenal gland which is secreting cortisol (adrenal adenoma or carcinoma)
do distinguid between ectopic ACTH production and an adrenal adenoma
Measure ACTH levels
- if caused by ectopic ACTH production ACTH levels will be high
- if caused by an adrenal neoplasia ACTH levels are low because of the affect of negative feedback
if ACTH levels high
get a chest CT
If ACTH levels low
get an abdominal CT
management od cushings syndrome
depends on the underlying cause
the best treatment for any form of tumour causing cushings syndrome
is surgical ressection
if the tumour cannot be respected or has metastasised
- ketoconazole= which is an anti-fungal but in cushings works because it inhibits cytochrome P450 which is involved with steroid synthesis
- metyrapone
if cushings syndrome is caused b exogenous steroids
slowly reduce the dose of steroids over time and ideally get them to a point where they cn be stopped
what should you never ever do in someone with cushings syndrome
never be a moron and stop there steroids immediately as you can cause an ADRENAL CRISIS which can kill the patient
