cushings syndrome

Question 1

defintion

Answer 1

clinical abnormalities which arise due to any state of prolonged excess cortisol

Question 2

cushings disease

Answer 2

refers specifically to a pituitary adenoma which is secreting ACTH and is a cause of cushings syndrome

Question 3

causes of cushings syndrome

Answer 3

divided into endogenous causes and exogenous causes

Question 4

endogenous causes

Answer 4

• pituitary adenoma secreting ACTH (cushings disease)
• tumours of the adrenal gland (adrenal adenomas, adrenal carcinomas)
• ectopic ACTH production (usually small cell lung cancer)

Question 5

exogenous causes

Answer 5

steroid medication/abuse (oral, topical, IV, inhaled)

Question 6

the hypothalamus

Answer 6

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

Question 7

the adrenal cortex is made up of 3 layers

Answer 7

• zona glomerulosa
• zona fasciculata
• zona reticularis

Question 8

ACTH specifically

Answer 8

stimulates the cells of the zona fasciculata to secrete cortisol

Question 9

cortisol belong to a family called

Answer 9

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

Question 10

the levels of free cortisol are

Answer 10

tightly controlled and if there is any excess it is secreted in the urine

Question 11

in times of stress the hypothalamus

Answer 11

secretes more CRH which in turn increases the amount of free cortisol in the blood

Question 12

free cortisol does many things

Answer 12

• 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

Question 13

cortisol works via a

Answer 13

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

Question 14

how are normal levels of cortisol achieved

Answer 14

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

Question 15

BUT in sucking syndrome

Answer 15

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

Question 16

proteolysis causes

Answer 16

• muscle breakdown causing myopathy (particularly proximal myopathy)
• bone breakdown using osteoporosis
• skin breakdown causing thinning of the skin, striae, and easy bruising

Question 17

gluconeogensis causes

Answer 17

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

Question 18

cushings syndrome causes hypertension by

Answer 18

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

Question 19

other characteristic features cause by excess adipose tissue

Answer 19

moon face, buffalo hump, supracalvicular fat pad

Question 20

other features of cushings

Answer 20

acne, amenorrhoea, hyperhydrosis, depression, increased susceptibility to infection, frontal balding in woman and depression

Question 21

initial test when you suspect cushings syndrome

Answer 21

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

Question 22

definitive test

Answer 22

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

Question 23

what could give you a false positive on dexamethasone suppression test

Answer 23

• anti-epileptic drugs (Phenytoin, carbamepazine), rifampicin, eating disorders, depression, alcoholics with drawing
• in these cases a 24 hour urine cortisol test is preferred

Question 24

once you have confirmed the diagnosis of cushings syndrome

Answer 24

move onto a high dose dexamethasone test to determine whether the cushings syndrome is caused by a pituitary adenoma secreting ACTH

Question 25

high dose dexamethasone suppression test

Answer 25

• 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

Question 26

if high dose dexamethasone test causes no change in cortisol levels the person has either a

Answer 26

• 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)

Question 27

do distinguid between ectopic ACTH production and an adrenal adenoma

Answer 27

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

Question 28

if ACTH levels high

Answer 28

get a chest CT

Question 29

If ACTH levels low

Answer 29

get an abdominal CT

Question 30

management od cushings syndrome

Answer 30

depends on the underlying cause

Question 31

the best treatment for any form of tumour causing cushings syndrome

Answer 31

is surgical ressection

Question 32

if the tumour cannot be respected or has metastasised

Answer 32

• ketoconazole= which is an anti-fungal but in cushings works because it inhibits cytochrome P450 which is involved with steroid synthesis
• metyrapone

Question 33

if cushings syndrome is caused b exogenous steroids

Answer 33

slowly reduce the dose of steroids over time and ideally get them to a point where they cn be stopped

Question 34

what should you never ever do in someone with cushings syndrome

Answer 34

never be a moron and stop there steroids immediately as you can cause an ADRENAL CRISIS which can kill the patient