Cushing's Syndrome

Question 1

what is the main pathophysiology of Cushing’s syndrome/disease

Answer 1

excess cortisol

Question 2

what other pathophysiology is seen in Cushing’s(other than the main one)

Answer 2

protein loss, altered carb/lipid metabolism(diabetes, obesity), altered psyche, excess mineralocorticoid, excess androgen

Question 3

what can excess mineralocorticoid and excess androgen lead to

Answer 3

excess mineralocorticoid = hypertension, oedema

excess androgen = virilism, hirsutism, acne, oligo/amennorrhoea

Question 4

what can protein loss lead to

Answer 4

myopathy(wasting), osteoporosis(fractures), thin skin(striae, bruising)

Question 5

what signs/symptoms is Cushing’s characterised by

Answer 5

think skin, proximal myopathy(shoulders, hips), frontal balding in women, conjunctival oedema, osteoporosis

Question 6

what is the difference between Cushing’s syndrome and Cushing’s disease

Answer 6

Syndrome = excess cortisol
Disease = excess cortisol due to pituitary cause

Question 7

how is the classical physique seen in Cushing’s described

Answer 7

as a lemon on matchsticks

Question 8

what is the theory behind the tests used to check for Cushing’s

Answer 8

too much cortisol, so cortisol suppressant test

give exogenous oral high dose steroid(eg dexamethasone) and see if endogenous secretion of cortisol decreases

Question 9

what different diagnostic tests can be used for Cushing’s

Answer 9

overnight 1mg dexamethasone suppression test(oral), urine free cortisol, diurnal cortisol variation or 2 day 2mg/day dexamethasone suppression test

Question 10

what is the diagnostic criteria for Cushing’s using the overnight 1mg dexamethasone suppression test

Answer 10

normal = <50nmol/l cortisol
Cushing’s = >130nmol/l cortisol
(same criteria as the 2 day test)

Question 11

what is the normal range for urine free cortisol(24hr urine collection)

Answer 11

total <250 cortisol is normal

Question 12

what is the aetiology of Cushing’s in the majority of cases

Answer 12

Cushing’s disease, ie pituitary pathology is causing excess cortisol
(ACTH dependant)

Question 13

what are the different aetiologies of Cushing’s syndrome

Answer 13

adrenal adenoma or carcinoma, ectopic ACTH production(lung thymus, pancreas), iatrogenic Cushing’s syndrome
(ACTH independent)

Question 14

what can cause false positives of Cushing’s syndrome

Answer 14

alcohol and depression, or steroid medication

Question 15

how can ACTH distinguish between pituitary, adrenal and ectopic causes of Cushing’s

Answer 15

pituitary = ACTH 25-300
adrenal = ACTH <1
ectopic = >300

Question 16

what test can be used to distinguish between pituitary(Cushing’s disease) and other Cushing’s causes

Answer 16

CRF test, increases ACTH and cortisol in pituitary only

Question 17

what non-pharmacological treatment can be used for Cushing’s disease

Answer 17

hypophysectomy(transphenoid route), external radiotherapy if recurs, or bilateral adrenalectomy if need be

Question 18

what non-pharmacological treatment can be used for adrenal or ectopic Cushing’s syndrome

Answer 18

adrenal = adrenalectomy
ectopic = remove source tumour, or bilateral adrenalectomy

Question 19

what pharmacological treatment is used most commonly for Cushing’s, and when would it be used

Answer 19

Metyrapone, if other treatments fail or waiting for radiotherapy to work, S/E common

Question 20

describe how Cushing’s syndrome can be iatrogenic

Answer 20

due to prolonged high dose steroid therapy, causes chronic suppression of pituitary ACTH production and adrenal atrophy

Question 21

what is the most common cause of Cushing’s syndrome

not disease

Answer 21

iatrogenic, due to prolonged high dose steroid

Question 22

what are the implications of adrenal suppression by long term exogenous steroids

Answer 22

unable to respond to stress(illness/surgery), need extra doses steroids when ill, cannot stop steroids suddenly, gradual withdrawal needed