Cushing's Disease Flashcards
What is cortisol derived from?
Cholesterol
Where are the receptors for cortisol?
Nuclear receptors
What is the axis which stimulates cortisol release?
- Hypothalamus - CRH
- Anterior pituitary - ACTH
- Adrenal cortex (zona fasciculata) - Cortisol
What are the effects of cortisol on muscle, liver and fat?
Muscle - Decreases insulin sensitivity, proteolysis and less protein synthesis.
Liver - Gluconeogenesis and glycogenolysis
Fat - Lipolysis and redistribution of fats
What is cortisols effect on immune response?
- Decreased
- Anti inflammatory
What is cushings syndrome?
- Clinical state produced by chronic glucocorticoid excess and loss of normal feedback mechanisms of the HPAA axis
- Loss of circadian rhythm of cortisol release (normally highest on waking)
What are the ACTH dependent causes of Cushing’s syndrome?
- Cushing’s Disease
- Bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma - Ectopic ACTH production
- Small cell lung cancer
- Carcinoid tumours - Ectopic CRH production (rare)
- Thyroid and prostate cancers
What are the ACTH independent causes of Cushing’s syndrome?
- Exogenous steroids
- Adrenal adenoma/cancer
- May cause abdo pain
- Virilisation in males - Adrenal nodular hyperplasia
What are symptoms of Cushing’s syndrome?
- Weight gain
- Mood change (depression, lethargy, irritability, psychosis)
- Proximal weakness
- Gonadal dysfunction (irregular menses, hirsutism, erectile dysfunction)
- Acne
- Recurrent achille’s tendon rupture
- Virilisation
What are the signs of Cushing’s syndrome?
- Central obesity
- Plethoric
- Moon shaped face
- Buffalo hump
- Supraclavicular fat distribution and muscle atrophy
- Bruises
- Purple abdominal striae
- Osteoporosis
- Raised BP
- Raised blood glucose
- Infection prone
- Poor healing
- Abdominal mass (underlying cause)
What symptoms of Cushing’s syndrome are specific to ectopic ACTH production?
- Pigmentation
- Hypokalemic metabolic alkalosis (raised mineralcorticoid)
- Weight loss
- Hyperglycaemia
Normal cushingoid features are absent
How would you investigate Cushing’s syndrome?
- Find raised plasma cortisol
- Dexamethasone suppression test
- Dexamethasone 1g PO at midnight, do serum cortisol at 8am
- No suppression in Cushing’s syndrome, normal is suppression to <50nmol/L
- 24hr urinary free cortisol is an alternative - 48hr Dexamethasone suppression test
- Give 0.5mg/6hr for 2 days
- Measure cortisol at 0 to 24hr
- Failure to suppress cortisol in cushing’s syndrome
- If given high dose 2mg/6hr, if there is suppression it shows it is a pituitary adenoma
- Can do midnight cortisol as an alternative
How would you localise the cause once Cushing’s syndrome is confirmed?
- Plasma ACTH
- If undetectable, adrenal tumour is likely
- Give CT/MRI of adrenal glands
- If no mass, do adrenal vein sampling - If ACTH is detectable, do high dose suppression test
- Distinguishes a pituitary adenoma from ectopic ACTH
- Suppression in pituitary adenoma - CRH test
- Cortisol will rise with pituitary disease but not ectopic ACTH - If pituitary disease suspected
- MRI of pituitary
- Bilateral inferior petrosal sinus blood sampling - If ectopic ACTH suspected
- IV contrast CT of chest, abdo, pelvis
- MRI of neck, thorax, abdomen
- Find the secreting carcinoid tumour
What is the treatment for iatrogenic Cushing’s syndrome?
- Stop medications if possible
What is the treatment for Cushing’s disease?
- Selective removal of pituitary adenoma trans-sphenoidally
