Cushing's Flashcards
what is the definition of cushings syndrome?
General term which refers to chronic excessive and inappropriate elevated levels of circulating CORTISOL whatever the cause
what is the definition of cushings disease?
Specifically refers to excess glucocorticoids resulting from inappropriate ACTH (adrenocorticotrophic hormone) secretion from the pituitary due to tumour
what is the epidemiology of Cushing’s syndrome?
- The most common cause is oral steroids i.e. glucocorticoid therapy
- Spontaneous endogenous causes are rare - of these 80% are due to raised ACTH; of these a pituitary adenoma (Cushing’s disease) is the commonest cause
- We normally have high-cortisol when:
• Alcohol pseudo-Cushing’s syndrome, depression, obesity and pregnancy
what is the aetiology of Cushing’s syndrome?
- ACTH-dependent causes (ACTH ↑):
• Cushing’s disease - most common ACTH-dependent cause: - Bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma (benign) (usually a microadenoma)
- Equal prevalence in both men and women
- Peak age is 30-50 yrs
• Ectopic ACTH production: - Essentially an ACTH producing tumours elsewhere in the body
- Especially small cell lung cancer and carcinoid tumours
• ACTH treatment for e.g. asthma - ACTH-independent causes (↓ ACTH due to negative feedback from raised cortisol):
• Adrenal adenoma (benign)/cancer - tumour of the adrenal that releases cortisol
• Iatrogenic such as administration of a glucocorticoid e.g. PREDNISOLONE
what are the rusk factors of cushing’s syndrome?
adrenal or pituitary tumours, long-term therapy with corticosteroids, and being female.
what is the brief pathophysiology of cushing’s syndrome?
- Excess cortisol can either result from excess ACTH which in turn stimulates excess cortisol release or from neoplasms in the adrenals which in turn stimulate the zona reticularis to release more cortisol
- Excess can also result from ingesting excess glucocorticoid itself e.g. PREDNISOLONE
what are the key presentations of cushing’s syndrome?
- Patients are obese:
• Fat distribution is typically central, affecting the trunk, abdomen and neck (buffalo hump) - high cortisol causes more fat around tummy - Plethoric complexion(ruddy and swollen) with moon face
- Mood change - depression, lethargy, irritability,
psychosis) - Proximal weakness
- Gonadal dysfunction (irregular periods and erectile dysfunction)
- Protein catabolic (breakdown) effects of cortisol:
• Muscle atrophy
• Thin skin that bruises easily
• Purple striae on the abdomen, breasts and thighs - Acne
- Increased BP
- Failure for children to grow tall despite excess weight
- Infections due to anti-inflammatory effect of cortisol and poor healing
- Osteoporosis
- Hyperglycaemia (impaired glucose tolerance)
what are the signs of cushing’s syndrome?
- Patients are obese:
• Fat distribution is typically central, affecting the trunk, abdomen and neck (buffalo hump) - high cortisol causes more fat around tummy - Plethoric complexion(ruddy and swollen) with moon face
- Protein catabolic (breakdown) effects of cortisol
- Increased BP
- Osteoporosis
- Hyperglycaemia (impaired glucose tolerance)
what are the symptoms of cushing’s syndrome?
Repeat infections, failure of growth in children, acne, purple stains on abdomen and thighs, thin skin, irregular periods, erectile dysfunction, mood changes, proximal weakness
whats are first line investigation for cushing’s syndrome?
random plasma cortisol
what are the gold standard investigations for cushing’s syndrome?
• Overnight dexamethasone suppression test:
- Oral dexamethasone 1mg at 00:00
- Measure serum cortisol at 8AM
- Normally there will be cortisol suppression < 50nmol/L
- In Cushing’s syndrome there will be no suppression
• Urine free cortisol over 24hrs is an alternative:
- Take > 2 measurements (cortisol is bound to albumin, when capacity is reached then will spill out to urine)
what other tests could be done for cushing’s syndrome?
• If there is no suppression
• Perform 48hr dexamethasone suppression test:
- Oral dexamethasone x4 a day for 2 days
- Measure cortisol at 0hrs and 48hrs
- In Cushing’s there will be no suppression of cortisol
- If the above tests are positive then do plasma ACTH
- If ACTH is undetectable - an adrenal tumour is likely:
• Perform CT/MRI adrenal glands to detect adenomas or carcinomas
• If no mass, then do adrenal vein sampling
- If ACTH is detectable then distinguish a pituitary cause from an ectopic ACTH production:
• Perform HIGH dose dexamethasone suppression test
• Or a corticotropin releasing hormone (CRH) test:
- Human IV CRH given
- Measure cortisol at 120 mins
- Cortisol will rise with pituitary disease but NOT with ectopic ACTH production
- If test shows that cortisol response to CRH, then Cushing’s disease is likely:
• Pituitary MRI to locate neoplasm
- If test shows that cortisol does not respond to CRH then hunt for the ectopic source of ACTH:
• IV contrast CT of chest, abdomen & pelvis
• MRI of neck, thorax and abdomen
• CXR to look at lungs for small cell lung cancer
what are the differential diagnoses for cushing’s syndrome?
Pseudo-Cushing’s syndrome - caused by alcohol excess, resolves after 1-3 weeks of alcohol abstinence
how is cushing’s syndrome managed?
- Iatrogenic - stop steroids!
- Cushing’s disease:
• Surgical selective removal of pituitary adenoma - trans-sphenoidal approach
• Bilateral adrenalectomy (remove both adrenal glands): - If source unlocatable or recurrence post-op
- Complication:
• Nelson’s syndrome: - Increase skin pigmentation due to significantly increased ACTH from an enlarging pituitary tumour as the adrenalectomy will remove the negative feedback
- Will respond to pituitary radiotherapy
- Adrenal adenoma - Adrenalectomy
- Adrenal carcinoma:
• Adrenalectomy (doesn’t cure cancer) so radiotherapy and adrenolytic drugs e.g. MITOTANE - Ectopic ACTH:
• Surgery if tumour is located and hasn’t spread
• Drugs that inhibit cortisone synthesis e.g. METYRAPONE, KETOCONAZOLE and FLUCONAZOLE are used pre-op or if awaiting effects of radiation
how is cushing’s syndrome monitored?
regular tests, tests to determine cause
