Cushing's Syndrome Flashcards
what 3 types of steroids does the adrenal cortex produce
glucocorticoids
mineralocorticoids
androgens
glucocorticoids
eg cortisol
affect carbohydrate, lipid and protein metabolism
mineralocorticoids
control Na and K balance eg aldosterone
androgens
sex hormones that have a weak effect until peripheral conversion to testosterone and dihydrotestosterone
cushing syndrome
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
describe cortisol secretion
what is the chief cause of cushings syndrome
oral steroids
cushing’s disease
pituitary adenoma causing increased ACTH
signs due to protein loss
myopathy and wasting - proximal
osteoperosis leading to fractures
thin skin, striae and bruising
other signs
altered carbohydrate/lipid metabolism, DM, central obesity, intrascapular and supraclavicular fat pads
buffalo hump
altered psyche, depression
moon face
plethoric - florid/red face
how does Cushing’s lead to DM
Glucocorticoid excess induces a stimulation of liver gluconeogenesis, and inhibition of insulin sensitivity
how does Cushings cause osteoporosis
increased cortisol causes a decrease in calcium
compensatory increase in PTH
what does excess mineralocorticoid cause
fluid and sodium retention:
hypertension and oedema
what does excess androgen cause
virilism
hirsutism
acne
oligo/amenorrhoea
what are the two ACTH dependent causes
cause increased ACTH
Cushing’s disease and ectopic ACTH production
cushing’s disease
ACTH secreting pituitary adenoma
more common in females
what are the majority of ACTH secreting pituitary adenomas
microadenomas
ectopic ACTH production
especially SCLC and carcinoid tumours
seen in the thymus, lung and pancreas
what are the ACTH independent causes
decreased ACTH due to negative feedback
adrenal adenoma or cancer
adrenal nodular hyperplasia - bilateral macronodular hyperplasia
pseudo Cushing’s
alcohol and depression and steroid medication can mimic Cushing’s and cause positive screening tests
what can alcohol cause
cushingoid appearance
what does confirmation of Cushing’s rest on
demonstrating inappropriate cortisol secretion, not suppressed by exogenous glucocorticoids (eg Dexamethasone)
outpatient screening test
overnight dexamethasone suppression test
- 1mg dexamethasone PO at midnight, serum cortisol performed at 8am
normal test/positive suppression: plasma cortisol <100nmol/L
what is the problem with overnight dexamethasone suppression test
there are some false positives
name 2 other screening tests
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
what is the formal diagnostic test
48h low dose dexamethasone suppression test
- normal/positive suppression results in plasma cortisol <50nmol/L on second sample
2 day 2 mg dose
what is used to evaluate the pituitary gland
MRI scan
what is used to lateralize the tumour prior to surgery
inferior petrosal sinus sampling
DD: what does a low ACTH suggest
non-ACTH dependent disease
likely to be adrenal in origin: adrenal adenoma/carcinoma or adrenal nodular hyperplasia
DD: what does a high ACTH suggest
need to distinguish beween Cushing’s disease and ectopic ACTH
DD: what is a classical ectopic ACTH syndrome presentation
short history
pigmentation and weight loss
unprovoked hypokalaemia
plasma ACTH levels > 300
DD: what does a rise in cortisol and ACTH on a CRH test indicate
a pituitary source (rather than ectopic)
DD: what is used to distinguish between pituitary and other sources
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
DD: what should be done if an adrenal tumour is suspected
CT the adrenal glands
management of Cushing’s disease
selective removal of pituitary adenoma (trans-sphenoidally)
bilateral adrenalectomy if the source is unlocatable/recurrence post-op
radiotherapy if recurs
trans sphenoidal approach
via the nasal cavities and sphenoid sinus
management of adrenal adenoma/carcinoma
adrenalectomy cures adenomas but rarely cures cancer
radiotherapy if cancer
management of ectopic ACTH
remove source
or bilateral adrenalectomy
metyrapone
inhibits cortisol production (and aldosterone to a lesser extent), this resuts in increased ACTH production and increased cortisol precursors
side effects are common
when is Metyrapone used
if other treatments fail, or when waiting for radiotherapy to work
Ketoconazole
classic anti-fungal drug
hepatotoxic
pasireotide
a new somatostatin analogue (blocks receptors 2 and 5)
what are the implications of prolonged steroid therapy
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.
