Cushing's Syndrome Flashcards
What is the pathophysiology?
What is the name of the rhythm that is lost?
Chronic glucocorticoid (i.e. cortisol) excess, with loss of normal feedback mechanisms by the hypothalamo-pituitary-adrenal axis.
Loss of circadian rhythm
A circadian rhythm is a natural, internal process that regulates the sleep-wake cycle and repeats roughly every 24 hours.
Cortisol is highest on waking
The physiological effect of cortisol:
- Why does gluconeogenesis increase?
- What does this lead to?
- What does it suppress?
Under stressful conditions, cortisol provides the body with glucose by tapping into protein stores via gluconeogenesis in the liver. This energy can help an individual fight or flee a stressor. However, elevated cortisol over the long term consistently produces glucose, leading to increased blood sugar levels.
The immune system
What is the main iatrogenic cause and why? - MOST COMMON CAUSE
Oral steroids - mimics affects of cortisol
Watch osmosis video on YT
ACTH-dependent causes (cause the adrenal gland to produce too much cortisol):
Cushing’s Disease is the main CAUSE. What is it?
What does that do to the adrenal glands?
What tumours produce ACTH?
Cushings syndrome causes by a pituitary adenoma - ACTH secreting pituitary adenoma
Bilateral adrenal hyperplasia
Small cell lung cancer, pancreatic or thymic carcinoid tumour - they secrete ACTH
ACTH-independent causes:
What is the main iatrogenic cause?
Where may a cortisol secreting tumour be?
Oral steroids
Adrenal adenoma/carcinoma/hyperplasia
S+S:
BiG SOFAS mneumonic - what does it stand for?
BP
i
Glucose
Skin Osteoporosis Fat Affect Sex
S+S:
Why are they prone to hypertension?
Why do they get hyperglycemic eventually leading to DM if left untreated?
Cortisol stimulates renal reabsorption of sodium (increased blood volume) and enhances vascular sensitivity to catecholamine and angiotensin II.
Under stressful conditions, cortisol provides the body with glucose by tapping into protein stores via gluconeogenesis in the liver. This energy can help an individual fight or flee a stressor. However, elevated cortisol over the long term consistently produces glucose, leading to increased blood sugar levels.
S+S:
Skin:
- Why do they get bruising?
- What may you see on their abdomen?
- What does high ACTH levels cause?
- Why should they not undergo surgery?
Due to thinning of the skin - more likely to burst vessels
Striae
Hyperpigmentation - This is due to melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from pro-opiomelanocortin (POMC).
Poor wound healing
S+S:
Why do they get osteoporosis? - 4
What may happen to their Achilles tendon?
Why do they have proximal weakness?
Increase bone resorption
Decrease bone formation
Depresses intestinal calcium absorption
Increase urinary calcium excretion
Rupture - they inhibit fibroblast proliferation and maturation, which is the likely explanation for the predisposition of patients with Cushing’s syndrome to spontaneous rupture of the Achilles tendon.
Due to proximal myopathy - legs are really skinny but fat in the centre
S+S:
Fat:
- What does their face look like?
- Where do they get a lot of fat deposition?
- A hump behind the shoulder can develop when fat gathers together behind your neck. What is the name for this?
- What proximal myopathy lead to the legs looking like?
‘Moon face’
Central obesity
Buffalo hump
Very wasted legs
S+S:
What psychological problems may they have?
Sex:
- How may it affect men trying to have children?
- How may it affect women trying to get pregnant?
- Why do they get hirsutism in ACTH dependent Cushing’s syndrome?
Altered mood Lethargy Psychosis --- Erectile dysfunction
Irregular periods
It results from the stimulating effect of ACTH on adrenal production of androgens.
Diagnostic tests - 1st line:
Why are serum cortisol levels not reliable?
Overnight dexamethasone suppression test:
- Dose given?
- What time is it given?
- How many hrs later is it rechecked?
- What means there is a positive result?
- What is an alternative to this?
Time of day has an influence - highest in the morning
Stress (from venepuncture) may influence results
1mg
Midnight or 11 p m
Has to be 8 hr period - so 9/8 am
Cortisol should become suppressed as it is being replaced - due to negative feedback
Positive If negative feedback is impaired meaning cortisol remains high
24 hr urine cortisol exertion test - if elevated can alsoo most on
Diagnostic tests - 2nd line - Only done if 1st line +ve:
48 hr LOW dose dexamethasone suppression test:
- Dose given?
- How many times a day?
- How many days?
- What means there is a positive result?
48 hr HIGH dose dexamethasone suppression test:
- Dose given?
- How many times a day?
- How many days?
- What does >50% suppression suggest?
How else may the cortisol levels be measured? - 2
Positive If negative feedback is impaired meaning cortisol remains high
0.5 mg/6h PO for 2 days
2mg/6h PO for 2 days
Pituitary adenoma
(Dexamethasone, which is like cortisol, lowers the amount of ACTH released by the pituitary gland. This, in turn, lowers the amount of cortisol released by the adrenal glands).
Late night cortisol cortisol
Midnight serum cortisol
Localisation tests - only done if 1st/2nd line +ve:
Plasma ATCH:
- If plasma ATCH is undetectable, what does this suggest?
- If plasma ATCH is detectable, what does this suggest?
Iatrogenic
An adrenal tumour is likely -
(Not a pituitary or ectopic ACTH producing tumour cause)
Means it a pituitary cause or ectopic cause - this is distinguished using the high dose suppression test
(ATCH producing tumour cause)
If it is high, you do a HIGH dose dexamethasone test - this should come after measuring ACTH instead of being 2nd line
Other tests:
Why does hyperkalemia happen?
Glucocorticoids (cortisol) bind the mineralocorticoid receptor in kidneys too.
A hypokalaemic metabolic alkalosis can also be seen, as a result of increased renal mineralocorticoid action from the excess cortisol.
This results in an increased exchange of sodium and water for potassium and H+, leading to a hypokalaemic metabolic alkalosis.
This picture is also seen in Conn’s syndrome.
