Cushing’s Syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol. Cushing’s Disease is used to refer to the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH. Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.


Cushing’s Syndrome Features

There are a large number of features of Cushing’s Syndrome, so they don’t easily fit in to the handy mnemonic. I find it easier to picture the patient as very round in the middle with thin, weak limbs and then imagine the effects of high levels of stress hormone.

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


High levels of stress hormone:

  • Hypertension
  • Cardiac hypertrophy
  • Hyperglycaemia (Type 2 Diabetes)
  • Depression
  • Insomnia


Extra effects:

  • Osteoporosis
  • Easy bruising and poor skin healing


Causes of Cushing’s Syndrome

  • Exogenous steroids (in patients on long term high dose steroid medications)
  • Cushing’s Disease (a pituitary adenoma releasing excessive ACTH)
  • Adrenal Adenoma (a hormone secreting adrenal tumour)
  • Paraneoplastic Cushing’s


Paraneoplastic Cushing’s is when excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release. ACTH from somewhere other than the pituitary is called “ectopic ACTH”. Small Cell Lung Cancer is the most common cause of paraneoplastic Cushing’s.


Dexamethasone Suppression Tests (DST) 

You can find a video explaining this topic on the Zero to Finals YouTube channel as it can be a bit tricky to get your head around.

The dexamethasone suppression test is the test of choice for diagnosing Cushing’s Syndrome. This involves initially giving the patient the “low dose” test. If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.

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 to find out whether the dexamethasone suppresses their normal morning spike of cortisol.


Low Dose Dexamethasone Suppression Test (1mg dexamethasone)

A normal response is for the dexamethasone to suppress the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. The hypothalamus responds by reducing the CRH output. The pituitary responds by reducing the ACTH output. The lower CRH and ACTH levels result in a low cortisol level. When the cortisol level is not suppressed, this is the abnormal result seen in Cushing’s Syndrome.


High Dose Dexamethasone Suppression Test (8mg dexamethasone)

The high dose dexamethasone suppression test is performed after an abnormal result on the low dose test.

In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.

Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisone is not suppressed however ACTH is suppressed due to negative feedback on the hypothalamus and pituitary gland.

Where there is 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.



Pituitary Adenoma



Adrenal Adenoma

Not Suppressed


Ectopic ACTH

Not Suppressed

Not Suppressed


Other Investigations

24-hour urinary free cortisol can be used as an alternative to the dexamethasone suppression test to diagnose Cushing’s syndrome but does not indicate the underlying cause and is cumbersome to carry out.

  • FBC (raised white cells) and 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



The main treatment is to remove the underlying cause (surgically remove the tumour)

  • Trans-sphenoidal (through the nose) removal of pituitary adenoma
  • Surgical removal of adrenal tumour
  • Surgical removal of tumour producing ectopic ACTH


If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the patient replacement steroid hormones for life.


Last updated November 2018