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Cushing's Syndrome & Disease (Disease is a subset of Syndrome)…
Cushing's Syndrome & Disease
(Disease is a subset of Syndrome)
Clinical Presentation
Muscle atrophy
Think skin that bruises easily
Gonadal dysfunction (irregular periods and erectile dysfunction)
Purple striae on the abdomen, breasts and thighs
Proximal weakness
Acne
Mood change - depression, lethargy, irritability, psychosis
Increased BP
Moon face - swollen
Osteoporosis
Patients are obese
Fat distribution is typically central, affecting the trunk, abdomen and neck
High cortisol causes more fat around tummy
Hyperglycaemia
Key Facts
DISEASE
Specifically refers to excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary due to tumour
SYNDROME
General term which refers to chronic excess and inappropriate elevated levels of circulating CORTISOL whatever the cause
Alcohol excess mimics this
Functions of Cortisol
Increased carbohydrate and protein catabolism (breakdown)
Increased deposition of fat and glycogen
Na retention
Increased renal K loss
Diminished host response to infection
Investigations
Random plasma cortisol
If high then proceed to 1st line test
May mislead as illness, time of day and stress (e.g. due to venipuncture) will influence results
1st line test
Dexamethasone should result in reduced ACTH, therefore reduced cortisol
In Cushing's syndrome, there will be no suppression in an overnight test
Cortisol is bound to albumin, when capacity is reached then will spill out into the urine
Take careful drug history since can be caused by oral steroids
2nd line test (if there is no suppression)
Perform a 48hr dexamethasone suppression test - 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
If ACTH is detectable then distinguish a pituitary cause from an ectopic ACTH production
Treatment Plan
DRUGS which can be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland
Surgical treatment to remove pituitary tumours, adrenocortical tumours or removal of neoplastic tissue
Pituitary radiotherapy - associated with long term hypopituitarism
TAKE CAREFUL DRUG HISTORY - CAN BE CAUSED BY ORAL STEROIDS
Epidemiology
Spontaneous endogenous causes are rare - of these 80% are due to raised ACTH; of these a pituitary adenoma (Cushing's) is the commonest cause
Normally high cortisol - Alcohol, depression, obesity and pregnancy
The most common cause is oral steroids i.e. glucocorticoid therapy
Aetiology
ACTH-dependent causes
ACTH independent causes
Pathophysiology
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
Differential Diagnosis
Pseudo-Cushing's syndrome
Caused by alcohol excess, resolves after 1-3 weeks of alcohol abstinence