Cushing's syndrome Flashcards
1) What is Cushing’s syndrome?
2) What is Cushing’s disease?
1) A collections of signs and symptoms that occur when a patient has long term exposure too cortisol.
2) Where hypercortisolism is caused by an ACTH secreting pituitary adenoma.
1) When do cortisol levels normally drop and peak?
2) How does cortisol maintain BP?
3) During stress, what 3 processes does cortisol increase?
1) Normally peak in the morning and drop at night.
2) By increasing sensitivity of peripheral blood vessels to catecholamines.
3) Gluconeogenesis, proteolysis and lipolysis.
1) How does cortisol dampen inflammatory and immune responses?
2) What are the 2 classifications of causes of Cushing’s disease?
1) By decreased production of inflammatory mediators. Can also inhibit proliferation of T lymphocytes if levels are within normal range.
2) Exogenous and Endogenous.
1) What is the main exogenous cause of Cushing’s syndrome?
2) What is the mechanism of Cushing’s syndrome in the main exogenous cause?
1) Medications, mainly corticosteroids, used to treat autoimmune/ inflammatory disorders.
2) Exogenous steroids can cause negative feedback on the hypothalamus/pituitary gland causing decreased CRH/ ACTH which will shut down cortisol production in the zona fasciculata.
1) What is the most common endogenous cause of Cushing’s syndrome?
2) What is the mechanism of this cause?
1) Excess ACTH produced by a pituitary adenoma (Cushing’s disease).
2) This causes overstimulation of the zona fasciculata, causing it to secrete excess cortisol.
Name and describe 2 other endogenous causes of Cushing’s syndrome.
1) Ectopic sources of ACTH such as small cell lung cancers.
2) Adrenal gland tumour making excess cortisol (adrenal adenomas/ adrenal carcinomas). Here, adrenal cells divide abnormally and produce excess cortisol.
1) What is the basis of the pathophysiology behind Cushing’s syndrome?
2) What do the clinical manifestations of Cushing’s syndrome often depend on?
1) Cortisol levels are constantly higher than normal, and so the effects of the cortisol are exaggerated.
2) The degree of cortisol excess; as hypercortisolism increases physical manifestations worsen.
1) What is the effect of increased cortisol on muscle, bone and skin?
2) Describe the effect of increased cortisol on GnRH.
3) Why are individuals with increased cortisol more susceptible to infection?
4) What is the effect of increased cortisol levels on normal brain function?
1) Causes severe muscle, bone and skin breakdown.
2) Inhibits release of GnRH from the hypothalamus.
3) As cortisol dampens the inflammatory and immune response.
4) Can cause impairment of normal brain function.
How can high cortisol levels cause hypertension?
Because cortisol amplifies the effects of catecholamines on blood vessels and begins to cross-react with mineralocorticoid (aldosterone) receptors.
How can high cortisol levels lead to the development of central obesity
Elevated blood glucose levels lead to increased insulin levels.
Insulin preferentially targets adipocytes in the centre of the body.
Insulin activates lipoprotein lipase in these cells which helps adipocytes to accumulate more fat molecules.
This leads to central obesity.
Name 10 features which could be associated with the clinical presentation of Cushing’s disease.
Proximal muscle wasting and thin extremities Easy bruising Abdominal striae Fractures due to osteoporosis/ brittle bones Fat redistribution (round full moon face, buffalo hump, trunkal obesity) Hyperglycaemia HTN Increased CVD risk Increased vulnerability to infections Poor wound healing Increased risk of diabetes Amenorrhoea/ Hirsutism/ ED Psychiatric disturbances (depression most common) Acne Supraclavicular fat distribution Linear growth deceleration in children Unexplained nephrolithiasis
What are the options of confirmatory diagnostic tests for Cushing’s syndrome?
Late night salivary cortisol/ 24 hour urinary free cortisol/ 1mg overnight dexamethasone suppression test.
How does the dexamethasone suppression test work?
When dexamethasone is given, normally cortisol levels should drop as there is suppression of ACTH production. If the test shows levels >50nanomol/L, then it is positive for Cushing’s syndrome.
1) What electrolyte disturbances can commonly occur in patients with Cushing’s syndrome?
2) What imaging investigations might you order for a patient with Cushing’s syndrome?
1) Hypokalaemia, hypernatraemia and increased bicarbonate.
2) MRI of pituitary, CT of adrenal glands, CT TAP to identify any ectopic sites of ACTH production.
1) What does treatment of Cushing’s syndrome depend upon?
2) Surgical resection is the treatment of choice for which causes of Cushing’s syndrome?
1) The underlying cause.
2) Pituitary tumours, adrenocorticol tumours, removal of neoplastic tissue causing ectopic ACTH production.
