Cushing's syndrome

Last Review Date: April 5, 2017

What is it?

Cushing’s syndrome is a group of signs and symptoms caused by the body producing too much cortisol from the adrenal glands. There are two adrenal glands, one on top of each kidney. These glands are triangular in shape. The outer layer of the adrenal glands called the adrenal cortex produces not only cortisol but also aldosterone and the adrenal androgens, mainly dehydroepiandrosterone sulphate (DHEAS). Cushing’s syndrome can also be caused by a patient taking too much of a synthetic glucocorticoid (a steroid like cortisol) for another clinical condition and by other rare causes (see below).

Feedback system for cortisol production

The hypothalamus sends CRH (corticotropin-releasing hormone) to the pituitary, which responds by secreting ACTH. ACTH then causes the adrenals to release cortisol into the bloodstream.

Source: NIDDK Image library


Cushing’s syndrome can occur in anyone but more commonly it occurs in adults aged 20-50 years. It is more common in women.

There are several causes of Cushing’s syndrome:

  • Iatrogenic Cushing’s syndrome. When taking synthetic glucocorticoids in high doses and for a long time. These drugs, such as prednisolone and dexamethasone, act like cortisol
  • Cushing’s disease. A pituitary tumour that produces large amounts of adrenocorticotrophic hormone (ACTH)
  • Adrenal tumour. A tumour in the adrenal gland that produces too much cortisol
  • Adrenal nodular hyperplasia. When groups of cells, or nodules, in the adrenal gland produce too much cortisol
  • Ectopic ACTH. A tumour in the body, not associated with the pituitary gland (see cortisol), that produces too much ACTH. This ACTH stimulates the adrenal glands to produce too much cortisol
  • Ectopic CRH. A tumour in the body, not associated with the hypothalamus (see cortisol), that produces too much corticotrophin releasing hormone (CRH). This stimulates the pituitary to secrete large amounts of ACTH that in turn stimulates the adrenal glands to produce too much cortisol
  • In some rare cases Cushing’s syndrome may develop because of gene mutations associated with other clinical conditions. For example a person may have an inherited gene mutation, such as Multiple Endocrine Neoplasia Type 1 or MEN-1, which increases the risk of developing tumours throughout the endocrine system, including pituitary and adrenal tumours.

The first two causes of Cushing’s syndrome are the most common.

There are many symptoms and signs associated with Cushing’s syndrome (see symptoms).

Symptoms of Cushing's syndrome

The signs and symptoms that occur with Cushing’s syndrome depend on a number of factors that include the cause of the Cushing’s syndrome, the level of cortisol or ACTH, the age and sex of the patient.

They include:

  • obesity around the waist and also fat laid down across the shoulders and neck; arms and legs tend to be thin
  • the face may be round and flushed
  • bruising is commonly present especially on the legs
  • wounds may heal very slowly
  • there may be muscle weakness
  • tiredness
  • ‘stretch’ marks around the stomach, hips and thighs
  • pigmentation of the skin, particularly of scars and inside the mouth
  • thin fragile skin that bruises easily
  • raised blood pressure (hypertension)
  • raised blood sugar (diabetes)
  • fragile bones (osteoporosis)
  • women usually have menstrual irregularities


When the clinician suspects a patient may have Cushing’s syndrome they will carry out one or more screening tests. If the screening test indicates the patient has Cushing’s syndrome, or when the test is borderline, other tests are carried out.

Screening tests

  • A 24-hour urine test — a positive test is when the urine contains more cortisol than normal. The reliability of the test depends on the patient taking an accurate 24 hour urine collection
  • An overnight dexamethasone test — the patient takes a tablet containing 1mg dexamethasone at about 11pm at home. Blood is taken the next morning in outpatients for cortisol measurement. In a normal person the dexamethasone (a synthetic glucocorticoid that acts like cortisol) will cause the blood cortisol to be low in the morning
  • Blood and/or salivary cortisol measurements at 9am and midnight — in the normal person the blood cortisol level is high in the morning and low at midnight. In the patient with Cushing’s syndrome the midnight cortisol level in the blood will also be high. It is usually only possible to perform a blood test at midnight if the patient is already in hospital. However, some laboratories are able to measure the cortisol level on a sample of saliva. In this case, the patient is given a small device to allow them to provide a saliva sample at midnight at home. This is not only more convenient, it also much less stressful than a blood test. This is important because just the stress of having a blood test can raise the cortisol level. ACTH may also be measured on the 9am blood sample.

There are several reasons, such as drugs, anxiety and obesity, why the test may not be entirely reliable and the clinician will carry out more tests. If a screening test is positive further tests are carried out to determine the cause of the Cushing’s syndrome.

Further tests

  • ACTH — blood is taken at 9am. ACTH will be low if Cushing’s syndrome is due to too much cortisol from an adrenal tumour or if the patient is taking synthetic steroids.
  • Extended dexamethasone test — This test is used to distinguish ACTH from either an ectopic tumour or from a pituitary tumour. Dexamethasone is given at different doses, four times a day, over four days. In the normal person, dexamethasone will suppress ACTH secretion and hence cortisol secretion (see cortisol). Ectopic ACTH production will not normally suppress with high doses of dexamethasone whereas ACTH from a pituitary tumour usually does.

Non-laboratory tests

  • Computed tomography (CT) scan — this is used to examine the pituitary, adrenal glands and other parts of the body for tumours
  • Magnetic Resonance Imaging (MRI) — this is used to examine the pituitary and adrenal glands for tumours.
  • Octreotide scan – a drug called octreotide, similar to somatostatin, is labelled with a radioactive tag and injected into the person tested; the radioactive drug attaches to receptors on the hormone-producing tumour, allowing detection with a radiologic scan.

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The aim of treatment is to remove the cause of the excess cortisol production. The type of treatment will depend on the cause.

If the cause is due to too much synthetic glucocorticoid the patient’s doctor will try to reduce the dose of the steroid to reduce the symptoms of Cushing’s syndrome. It may not be possible to stop the symptoms completely. The patient must never stop taking the steroids abruptly and should only reduce the dose under the direction of their doctor.

If the cause is due to an ACTH-producing tumour or ectopic ACTH production (see Cushing’s syndrome, "What is it?") surgery, radiation, and in the latter case, chemotherapy may be carried out.

If the cause is due to an adrenal tumour, or over production of cortisol by one adrenal, then surgical removal of that adrenal will often bring the cortisol levels back to normal. For a time, synthetic glucocorticoids may have to be taken since the activity of the other adrenal gland may have been suppressed by the excess cortisol. It may be many months before the synthetic steroids can be stopped. Again the patient should only change the dose or stop these steroids under the direction of their doctor.

Related pages

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Tests: Cortisol, ACTH
Condition: Hypertension

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