Cushing's

Question 1

cushings

Answer 1

caused by prolonged exposure to endogenous or exogenous glucocorticoids
degree of cortisol overproduction variable
significant morbidity and mortality

Question 2

causes

Answer 2

adrenocorticotropic hormone (ACTH)- dependent disease:
excessive ACTH from the pituitary (Cushing's disease), ectopic ACTH-producing tumours or excess ACTH administration

non-ACTH-dependent:
adrenal adenomas, adrenal carcinomas, excess glucocorticoid administration

Question 3

glucocorticoids

Answer 3

reduce inflammation - used to treat asthma, autoimmune, sepsis
bind to glucocorticoid receptor which upregulates the expression of anti-inflammatory proteins in the nucleus, and suppresses proinflammatory proteins in the cytosol

produced in the zona fasciculata of the adrenal cortex

cortisol is the most important

Question 4

glucocorticoid drugs

Answer 4

beclomethasone
betamethasone
budesonide
cortisone
dexamethasone
hydrocortisone
methylprednisolone
prednisolone

Question 5

epidemiology

Answer 5

10-15 per 1,000,000
higher incidence in DM, obesity, HTN, osteoporosis
in obese patients with T2DM, esp with poor glucose control and HTN, reported prevalence is 2-5%

Question 6

risk factors

Answer 6

due to adrenal or pituitary tumour is more common in females (5:1), with peak incidence between 25-40yo

ectopic ACTH production due to lung Ca occurs later in life

Question 7

common causes

Answer 7

use of exogenous glucocorticoids

endogenous cushing’s is split into corticotropin-dependent and corticotropin-independent causes

dependent (80-85%):
80% due to pituitary adenomas (cushing’s disease)
20% due to ectopic corticotropin syndrome, usually due to a SCLC and bronchial carcinoid tumours, but may occur with any endocrine tumour

independent:
most often due to a unilateral tumour: adrenal adenoma in 60%, adrenal carcinoma in 40%
very rare adrenal causes of cushing’s are corticotropin-dependent macronodular adrenal hyperplasia, primary pigmented nodular adrenal disease and McCune-Albright syndrome

Question 8

presentation

Answer 8

truncal obesity, supraclavicular fat pads, buffalo hump, weight gain
facial fullness, moon face, facial plethora
proximal muscle wasting and weakness
DM or impaired glucose tolerance
gonadal dysfunction, reduced libido
HTN
nephrolithiasis (renal calculi)
skin atrophy, purple striae, easy bruising, hirsutism, acne, pigmentation (with ACTH-dependent)
depression, cognitive dysfunction, emotional lability
osteopenia, osteoporosis
oedema
irregular menses
thirst, polydipsia, polyuria
impaired immune function, difficulty with wound healing

Question 9

DDx

Answer 9

chronic severe anxiety/depression
prolonged excess alcohol consumption (can cause a cushingoid appearance)
obesity
poorly controlled diabetes
HIV

Question 10

investigations

Answer 10

no single test is perfect
often needs several
should be performed when there is no acute concurrent illness as they can lead to false positives

FBC - raised WCC
electrolytes and acid-base balance - hypokalaemia and metabolic acidosis
24h urinary free cortisol
low dose dexamethasone suppression test
midnight cortisol levels

Question 11

management

Answer 11

definitive treatment of endogenous cushing’s syndrome requires tumour resection
increased risk due to metabolic consequences of cushing’s: tissue fragility, poor wound healing, HTN, DM

metyrapone, ketoconazole, mitotane all used to lower cortisol levels by inhibiting synthesis and secretion by the adrenal

Question 12

complications of cushing’s syndrome

Answer 12

metabolic syndrome
HTN
impaired glucose tolerance and diabetes
obesity
hyperlipidaemia
coagulopathy: thrombophilia
perforated viscera
impaired immunity
nelson's syndrome (tumours develop after adrenalectomy)

Question 13

prognosis

Answer 13

poorly controlled = 5 fold increase in mortality due to:
vascular disease (MI/stroke)
uncontrolled DM and its complications
infections

usual course is chronic, with cyclic exacerbations and rare remissions