Cushing's Flashcards
What is Cushing syndrome?
Endocrine disorder with elevated cortisol levels in the blood
What is Cushing disease?
Pituitary adenoma making excess ACTH, causing elevated cortisol
How are cortisol levels maintained in normal range?
By negative feedback
High levels of cortisol –> hypothalamus and pituitary gland decrease secretion of CRH and ACTH
- -> less CRH tells pituitary to release less ACTH –> zona fasciculata less stimulation to make cortisol
- -> cortisol levels go down
Adrenal cortex is divided into…
Zona glomerulosa
Zona fasciculata (widest zone, middle zone)
Zona reticularis
Which part of the adrenal cortex releases cortisol?
Zona fasciculata
When does cortisol peak?
In morning (“get up and go”), drops in evening
Effects of cortisol
Increases gluconeogenesis, proteolysis and lipolysis Maintains BP Dampens immune + inflammatory responses Unclear effect on mood and memory Inhibits bone formation
How does cortisol maintain BP?
Increasing sensitivity of peripheral blood vessels to catecholamines (adrenaline and noradrenaline) which narrow blood vessel lumen
How does cortisol dampen immune/inflammatory response?
Reduces production and release of prostaglandins and ILs
Inhibits proliferation of T lymphocytes
Normal process of hypothalamus-pituitary-adrenal axis for cortisol release
Hypothalamus secretes corticotrophin releasing hormone
- -> stimulates pituitary gland to secrete adrenocorticotropic hormone
- -> targets cells in adrenal cortex to secrete cortisol
Explain the effects of constantly high cortisol levels (i.e. Cushing syndrome)
Muscle, bone and skin breakdown
Elevated glucose levels which leads to high insulin levels - insulin targets adipocytes in centre of body and activates lipoprotein lipase causing fat accumulation
Hypertension - due to amplifying effect of catecholamines AND binding to mineralocorticoid receptors
Inhibit gondatrophin-releasing hormone
Dampens inflammatory/immune response
Impair brain function
What does the zona glomerulosa release?
Mineralocorticoid
Mineralocorticoid effect
Increases blood pressure by retaining fluid
Exogenous causes of Cushing syndrome
Medications - e.g. steroids
Explain how exogenous steriods can cause Cushing syndrome
Similar to cortisol so mimics effects on tissues
Also it has a negative feedback effect, causing less CRH and ACTH and this effects the zona fasciculata
Less cortisol is produced and the zona fasciulata shrinks over time
However, still massive amounts of exogenous steroids so get symptoms of high cortisol
Endogenous causes of Cushing syndrome
Excess ACTH - pituitary adenoma (benign), small cell lung cancer
Excess cortisol - adrenal adenoma, adrenal carcinoma
Explain how adenal tumours effect cortisol, ACTH, CRH and the size of the zona fasciculata
Cells divide abnormally and secrete excess cortisol
–> less CRH and ACTH from negative feedback
–> effects NORMAL cells in zona fasciculata which produce less cortisol and shrink
BUT…
The abnormal cells are autonomous and so aren’t effected by this negative feedback, so overall net effect = too much cortisol
Symptoms/signs of Cushing’s
Muscle wasting Thin extremities Skin thinning Easy bruising Abdominal striae Fractures (osteoporosis) Fat redistribution - round full moon shaped face, buffalo hump, truncal obesity Hyperglycaemia - can lead to DM Hypertension Poor immune system
Diagnosis of Cushing’s
24 hour urinary free cortisol
9am and midnight ACTH and cortisol levels
Overnight dexamethasone suppression test
MRI of pituitary, CT adrenals CT chest abdo pelvis (if appropriate)
What is low dose dexamethasone suppression test?
Normal result
Given low dose of dexamethasone (1mg at 10pm) –> suppresses ACTH production
Should cause a decrease in serum cortisol levels - measured at 9am
Dexamethasone suppression test
- endogenous Cushing’s results
Cortisol remains high
Explain HIGH DOSE dexamethasone test
Given 8mg dexamethasone
Pituitary adenoma responds to high dose - reduces ACTH and cortisol
Adrenal adenoma/carcinoma - reduces ACTH, but not cortisol as this is being released autonomously
Small cell lung cancer - stops ACTH from pituitary BUT still have ACTH being released elsewhere, so cortisol still high (and so is overall ACTH)
Treatment of Cushing’s
Gradually decrease steroid medications (to avoid adrenal crisis)
Surgical excision of adenoma
Adrenal steroid inhibitors - ketoconazole, metyrapone
High dose dexamethasone suppression test results with pituitary adenoma
Low ACTH
Low cortisol
