Cushing's syndrome Flashcards
What is the main biochemical feature of Cushing’s syndrome?
Prolonged high levels of glucocorticoids
What are the two groups of corticosteroid hormones?
Glucocorticoids
Mineralocorticoids
What is the name of the glucocorticoid hormone produced by the adrenal glands?
Cortisol
What is Cushing’s disease?
A pituitary adenoma that secretes excessive adrenocorticotropic hormone (ACTH)_which stimulates excessive cortisol release from the adrenal glands
Where is cortisol released from?
Adrenal glands
What drug can cause Cushing’s syndrome when used for a prolonged period of time?
Exogenous corticosteroids (prednisolone, dexamethasone)
Give common clinical features of Cushing’s syndrome?
Round face - ‘moon face’
Central obesity
Abdominal striae
‘buffalo hump’
Proximal limb muscle wasting
Easy bruising / poor skin healing
Hyperpigmentation of the skin
What are the causes of Cushing’s syndrome?
Use the CAPE mnemonic
Cushing’s disease - pituitary adenoma
Adrenal adenoma
Paraneoplastic syndrome
Exogenous steroids
When does paraneoplastic Cushing’s syndrome occur?
Give an example?
When ACTH is released from a tumour somewhere other than the pituitary gland
in small-cell lung cancer
How does high levels of ACTH cause skin pigmentation?
It stimulates melanocytes in the skin to produce melanin
If a patient has skin pigmentation and is thought to have Cushing’s disease, what is the likely diagnosis?
Cushing’s disease
OR
Ectopic ACTH (paraneoplastic)
What test is used to diagnose Cushing’s syndrome?
Dexamethasone suppression test
What is the normal response to dexamethasone?
Suppressed cortisol due to negative feedback
When would you do a low-dose overnight dexamethasone test?
As a screening test to exclude Cushing’s syndrome
When would you do a low-dose 48-hour dexamethasone test?
When Cushing’s syndrome is suspected
When would you do a high-dose 48-hour dexamethasone test?
To determine the cause in patients with confirmed Cushing’s syndrome
How is a low-dose overnight test carried out?
1mg dexamethasone is given at night and the cortisol levels are measure at 9am the following morning
How is a low-dose 48 hour test carried out?
0.5mg dexamethasone is taken every 6 hours for 8 doses, the cortisol level is measured at 9am on the third morning
How is a high-dose 48-hour test carried out?
2mg dexamethasone is taken every 6 hours for 8 doses, the cortisol level is measured at 9am on the third morning
How does a high-dose 48-hour dexamethasone test determine the cause of Cushing’s syndrome?
The higher dexamethasone dose is enough to suppress cortisol in those with a pituitary adenoma, but not those with an adrenal adenoma or ectopic ACTH
What happens to ACTH levels in a patient with an adrenal tumour?
It is suppressed
What happens to ACTH levels in a patient with an pituitary tumour?
It is elevated
What happens to ACTH levels in a patient with ectopic ACTH?
It is elevated
What other investigations may be done in Cushing’s syndrome?
Brain MRI - pituitary adenoma
CT abdomen - adrenal tumour
CT chest - small cell lung cancer
FBC - may show high WBCs
What is the preferred treatment for a pituitary adenoma?
Trans-sphenoidal surgery
What is the preferred treatment for an adrenal adenoma?
Surgical removal of the tumour(s)
What is the preferred treatment for a patient with ectopic ACTH?
Surgical removal of the tumour that is producing the ACTH
If surgical removal of causative tumour(s) is non-viable what treatment should be carried out?
Surgical removal of the adrenal glands (adrenalectomy) and life-long steroid replacement therapy
What is Nelson’s syndrome?
The development of an ACTH-producing pituitary tumour after adrenalectomy
This is due to a lack of cortisol and negative feedback
What does Nelson’s syndrome cause?
Skin pigmentation (high ACTH)
Bitemporal hemianopia
Lack of pituitary hormones
What is metyrapone?
When is it used?
A drug that reduces the production of cortisol in the adrenal glands
It is occasionally used in the treatment of Cushing’s
