Cushings Flashcards
What are the common causes of Cushing’s syndrome?
Exogenous causes (e.g. glucocorticoid therapy) are far more common than endogenous ones.
What is Cushing’s disease?
Cushing’s disease is caused by a pituitary tumour secreting ACTH, leading to adrenal hyperplasia.
It accounts for 80% of ACTH dependent causes.
What is a common ectopic ACTH production cause?
Small cell lung cancer is the most common cause of ectopic ACTH production.
It accounts for 5-10% of ACTH dependent causes.
What are the ACTH independent causes of Cushing’s syndrome?
Iatrogenic (steroids), adrenal adenoma (5-10%), adrenal carcinoma (rare), Carney complex, and micronodular adrenal dysplasia (very rare).
What is Pseudo-Cushing’s?
Pseudo-Cushing’s mimics Cushing’s syndrome and is often due to alcohol excess or severe depression.
What tests may show false positives in Pseudo-Cushing’s?
The dexamethasone suppression test or 24 hr urinary free cortisol may show false positives.
An insulin stress test may be used to differentiate.
What is Cushing’s syndrome?
Cushing’s syndrome is a condition caused by excessive cortisol production.
What are the general lab findings consistent with Cushing’s syndrome?
A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
What is a characteristic finding in ectopic ACTH secretion?
Ectopic ACTH secretion is characteristically associated with very low potassium levels.
What are the three most commonly used tests to confirm Cushing’s syndrome?
- Overnight (low-dose) dexamethasone suppression test
- 24 hr urinary free cortisol
- Bedtime salivary cortisol
What does the overnight dexamethasone suppression test indicate?
Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed.
What is the first-line localisation test for Cushing’s syndrome?
9am and midnight plasma ACTH (and cortisol) levels.
What does suppressed ACTH indicate in localisation tests?
If ACTH is suppressed, a non-ACTH dependent cause is likely, such as an adrenal adenoma.
How is the high-dose dexamethasone suppression test interpreted?
Cortisol and ACTH levels are used to differentiate causes of Cushing’s syndrome.
Interpretation:
- Not suppressed/Suppressed: Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
- Suppressed/Suppressed: Cushing’s disease (pituitary adenoma → ACTH secretion)
- Not suppressed/Not suppressed: Ectopic ACTH syndrome
What does CRH stimulation test indicate?
If the source is pituitary, cortisol rises; if ectopic/adrenal, there is no change in cortisol.
What is the purpose of petrosal sinus sampling of ACTH?
It may be needed to differentiate between pituitary and ectopic ACTH secretion.
What is the insulin stress test used for?
It is used to differentiate between true Cushing’s and pseudo-Cushing’s.
Summarise Cushing’s syndrome: causes
Cushing’s syndrome: causes
It should be noted that exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.
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 is the most common causes
ACTH independent causes
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
Pseudo-Cushing’s
mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
Summarise Cushing’s syndrome investigations
Cushing’s syndrome: investigations
This section will consider:
the general lab findings consistent with Cushing’s syndrome
tests to confirm whether a patient indeed has Cushing’s syndrome
tests to find the underlying cause of Cushing’s syndrome
It is useful to bear in mind the possible causes:
iatrogenic: corticosteroid therapy
ACTH-dependent causes
Cushing’s disease (a pituitary adenoma → ACTH secretion)
ectopic ACTH secretion secondary to a malignancy
ACTH-independent causes
adrenal adenoma
General findings consistent with Cushing’s syndrome
A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels.
Tests to confirm Cushing’s syndrome
The three most commonly used tests are:
overnight (low-dose) dexamethasone suppression test
this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
patients with Cushing’s syndrome do not have their morning cortisol spike suppressed
24 hr urinary free cortisol
two measurements are required
bedtime salivary cortisol
two measurements are required
Localisation tests
The first-line localisation is 9am and midnight plasma ACTH (and cortisol) levels. If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma
High-dose dexamethasone suppression test
The high-dose dexamethasone suppression test may be used to localise the pathology resulting in Cushing’s syndrome. This test may be interpreted as follows:
Cortisol ACTH Interpretation
Not suppressed Suppressed Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
Suppressed Suppressed Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)
Not suppressed Not suppressed Ectopic ACTH syndrome
Other tests
CRH stimulation
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol
Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.
An insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’s.
Summarise Cushing’s syndrome investigations
Cushing’s syndrome: investigations
This section will consider:
the general lab findings consistent with Cushing’s syndrome
tests to confirm whether a patient indeed has Cushing’s syndrome
tests to find the underlying cause of Cushing’s syndrome
It is useful to bear in mind the possible causes:
iatrogenic: corticosteroid therapy
ACTH-dependent causes
Cushing’s disease (a pituitary adenoma → ACTH secretion)
ectopic ACTH secretion secondary to a malignancy
ACTH-independent causes
adrenal adenoma
General findings consistent with Cushing’s syndrome
A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels.
Tests to confirm Cushing’s syndrome
The three most commonly used tests are:
overnight (low-dose) dexamethasone suppression test
this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
patients with Cushing’s syndrome do not have their morning cortisol spike suppressed
24 hr urinary free cortisol
two measurements are required
bedtime salivary cortisol
two measurements are required
Localisation tests
The first-line localisation is 9am and midnight plasma ACTH (and cortisol) levels. If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma
High-dose dexamethasone suppression test
The high-dose dexamethasone suppression test may be used to localise the pathology resulting in Cushing’s syndrome. This test may be interpreted as follows:
Cortisol ACTH Interpretation
Not suppressed Suppressed Cushing’s syndrome due to other causes (e.g. adrenal adenomas)
Suppressed Suppressed Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)
Not suppressed Not suppressed Ectopic ACTH syndrome
Other tests
CRH stimulation
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol
Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.
An insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’s.
