Cushing's Syndrome

Question 1

what 3 types of steroids does the adrenal cortex produce

Answer 1

glucocorticoids

mineralocorticoids

androgens

Question 2

glucocorticoids

Answer 2

eg cortisol

affect carbohydrate, lipid and protein metabolism

Question 3

mineralocorticoids

Answer 3

control Na and K balance eg aldosterone

Question 4

androgens

Answer 4

sex hormones that have a weak effect until peripheral conversion to testosterone and dihydrotestosterone

Question 5

cushing syndrome

Answer 5

the clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the HPA axis and loss of circadian rhythm in cortical secretion

Question 6

describe cortisol secretion

Answer 6

Question 7

what is the chief cause of cushings syndrome

Answer 7

oral steroids

Question 8

cushing’s disease

Answer 8

pituitary adenoma causing increased ACTH

Question 9

signs due to protein loss

Answer 9

myopathy and wasting - proximal

osteoperosis leading to fractures

thin skin, striae and bruising

Question 10

other signs

Answer 10

altered carbohydrate/lipid metabolism, DM, central obesity, intrascapular and supraclavicular fat pads

buffalo hump

altered psyche, depression

moon face

plethoric - florid/red face

Question 11

how does Cushing’s lead to DM

Answer 11

Glucocorticoid excess induces a stimulation of liver gluconeogenesis, and inhibition of insulin sensitivity

Question 12

how does Cushings cause osteoporosis

Answer 12

increased cortisol causes a decrease in calcium

compensatory increase in PTH

Question 13

what does excess mineralocorticoid cause

Answer 13

fluid and sodium retention:

hypertension and oedema

Question 14

what does excess androgen cause

Answer 14

virilism

hirsutism

acne

oligo/amenorrhoea

Question 15

what are the two ACTH dependent causes

Answer 15

cause increased ACTH

Cushing’s disease and ectopic ACTH production

Question 16

cushing’s disease

Answer 16

ACTH secreting pituitary adenoma

more common in females

Question 17

what are the majority of ACTH secreting pituitary adenomas

Answer 17

microadenomas

Question 18

ectopic ACTH production

Answer 18

especially SCLC and carcinoid tumours

seen in the thymus, lung and pancreas

Question 19

what are the ACTH independent causes

Answer 19

decreased ACTH due to negative feedback

adrenal adenoma or cancer

adrenal nodular hyperplasia - bilateral macronodular hyperplasia

Question 20

pseudo Cushing’s

Answer 20

alcohol and depression and steroid medication can mimic Cushing’s and cause positive screening tests

Question 21

what can alcohol cause

Answer 21

cushingoid appearance

Question 22

what does confirmation of Cushing’s rest on

Answer 22

demonstrating inappropriate cortisol secretion, not suppressed by exogenous glucocorticoids (eg Dexamethasone)

Question 23

outpatient screening test

Answer 23

overnight dexamethasone suppression test

• 1mg dexamethasone PO at midnight, serum cortisol performed at 8am

normal test/positive suppression: plasma cortisol <100nmol/L

Question 24

what is the problem with overnight dexamethasone suppression test

Answer 24

there are some false positives

Question 25

name 2 other screening tests

Answer 25

**24 hour urinary free cortisol** (a total of \<250 is normal and a cortisol/creatinine ratio of \<25 is normal) **Circadian rhythm** (cortisol taken at 0900 then 2400) - peaks in the morning and should be virtually 0 at midnight

Question 26

what is the formal diagnostic test

Answer 26

48h low dose dexamethasone suppression test - normal/positive suppression results in plasma cortisol \<50nmol/L on second sample 2 day 2 mg dose

Question 27

what is used to evaluate the pituitary gland

Answer 27

MRI scan

Question 28

what is used to lateralize the tumour prior to surgery

Answer 28

inferior petrosal sinus sampling

Question 29

DD: what does a low ACTH suggest

Answer 29

non-ACTH dependent disease likely to be adrenal in origin: adrenal adenoma/carcinoma or adrenal nodular hyperplasia

Question 30

DD: what does a high ACTH suggest

Answer 30

need to distinguish beween Cushing's disease and ectopic ACTH

Question 31

DD: what is a classical ectopic ACTH syndrome presentation

Answer 31

short history pigmentation and weight loss unprovoked hypokalaemia plasma **ACTH levels \> 300**

Question 32

DD: what does a rise in cortisol and ACTH on a CRH test indicate

Answer 32

a pituitary source (rather than ectopic)

Question 33

DD: what is used to distinguish between pituitary and other sources

Answer 33

a high dose Dexamethasone test (4x the dose of the low test) - failure of significant plasma cortisol suppression indicates an ectopic source of ACTH or an adrenal tumour

Question 34

DD: what should be done if an adrenal tumour is suspected

Answer 34

CT the adrenal glands

Question 35

management of Cushing's disease

Answer 35

selective removal of pituitary adenoma (trans-sphenoidally) bilateral adrenalectomy if the source is unlocatable/recurrence post-op radiotherapy if recurs

Question 36

trans sphenoidal approach

Answer 36

via the nasal cavities and sphenoid sinus

Question 37

management of adrenal adenoma/carcinoma

Answer 37

adrenalectomy cures adenomas but rarely cures cancer radiotherapy if cancer

Question 38

management of ectopic ACTH

Answer 38

remove source or bilateral adrenalectomy

Question 39

metyrapone

Answer 39

inhibits cortisol production (and aldosterone to a lesser extent), this resuts in increased ACTH production and increased cortisol precursors side effects are common

Question 40

when is Metyrapone used

Answer 40

if other treatments fail, or when waiting for radiotherapy to work

Question 41

Ketoconazole

Answer 41

classic anti-fungal drug hepatotoxic

Question 42

pasireotide

Answer 42

a new somatostatin analogue (blocks receptors 2 and 5)

Question 43

what are the implications of prolonged steroid therapy

Answer 43

**chronic suppression of pituitary ACTH production (negative feedback) and atrophy of the adrenal cortex.** The implications of this are: * One is unable to respond to stress (e.g. illness/surgery) * Extra doses of steroid are required when one is ill or having a surgical procedure * Steroids must not be stopped suddenly, there must be a gradual withdrawal over 4-6 weeks.