What causes of Cushing’s syndrome are more common: endogenous or exogenous
exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.
ACTH dependent causes of Cushing’s
ACTH dependent causes
- Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
- ectopic ACTH production (5-10%): e.g. small cell lung cancer
ACTH independent causes of Cushing’s
ACTH independent causes
- iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- Carney complex: syndrome including cardiac myxoma
- micronodular adrenal dysplasia (very rare)
What’s Carney complex?
Carney complex: syndrome including cardiac myxoma
What’s Pseudo - Cushing’s? + cause
Pseudo-Cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
What test results may be seen in Pseudo-Cushing’s?
What test is used to differentiate?
- causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
- insulin stress test may be used to differentiate
What electrolyte abnormality can be seen along with impaired glucose tolerance in Cushing’s?
hypokalemic metabolic alkalosis
What metabolic abnormality is associated with Cushing’s linked to ectopic ACTH secretion in small cell lung ca?
very low potassium
Test to differentiate between Cushing’s and pseudo-Cushing
Insulin stress test
Two tests to confirm Cushing
- overnight dexamethasone suppression test (most sensitive)
- 24 hr urinary free cortisol
Cushing’s features (associated with limbs and obesity)
Round in the middle with thin limbs:
- Round “moon” face
- Central Obesity
- Abdominal striae
- Buffalo Hump (fat pad on upper back)
- Proximal limb muscle wasting
Features of Cushing associated with high levels of stress hormone
- hypertension
- insomnia
- depression
- cardiac hypertrophy
- hyperglycaemia (T2DM)
Extra effects of Cushing (3)
- easy bruising
- poor wound healing
- osteoporosis
Times of dexamethasone test
What’s the aim
- To perform the test the patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am)
- The intention is the find out whether the dexamethasone suppresses their normal morning spike of cortisol.
What result on dexamethasone suppression test would exclude Cushing’s?
Low CRH (pituitary) and ACTH (cortisol production suppressed)
* this is due to negative feedback: dexamethasone suppressing production of CRH by hypothalamus and therefore ACTH from pituitary is suppressed as well
What are the doses of dexamethasone used in low and high dexamethasone supression tests?
Low dexamethasone: 1 mg
High: 8 mg
What if cortisol levels are not suppressed with low dexamethasone tests?
That implies Cushing’s syndrome -> we do high dexamethasone suppression test to localise
What results of the dexamethasone suppression test would be seen in Cushing’s Disease?
Cushing’s disease = pituitary adenoma
- still some negative feedback - on 8mg dexamethasone
Results on dexamethasone suppression test in adrenal adenoma
- Cortisol production is independent from the -> cortisone is not suppressed
- ACTH is suppressed due to negative feedback on the hypothalamus and pituitary gland
Results on dexamethasone suppression test in ectopic ACTH production
- ectopic ACTH* = e.g. from a small cell lung cancer
- neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland
Other investigations in Cushing’s disease
- 24 hour urinary free cortisol can be used as an alternative to the dexamethasone suppression test (does not indicate the location)
- FBC (raised white cells)
- electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
- MRI brain for pituitary adenoma
- Chest CT for small cell lung cancer
- Abdominal CT for adrenal tumours
What’s the main treatment for Cushing’s?
The main treatment is to remove the underlying cause (surgically remove the tumour)
Surgeries in Cushing’s disease (3)
*depending on location
- Trans-sphenoidal (through the nose) removal of pituitary adenoma
- Surgical removal of adrenal tumour
- Surgical removal of tumour producing ectopic ACTH
What if surgical options to remove the cause of Cushing’s are not possible?
- remove both adrenal glands
- give the patient replacement steroid hormones for life
