Cushing's syndrome

Cushing's syndrome is the name given to the collection of signs and symptoms that occur when the body is exposed to too much of the hormone cortisol.

Alternative names for Cushing’s syndrome

Hypercortisolism; Cushing syndrome

What is Cushing’s syndrome?

Photo of stretch marks on a woman suffering from Cushing's syndrome.

Photo of stretch marks on a woman suffering from Cushing's syndrome.

Cushing’s syndrome is the name of a disorder that occurs when the body is exposed to an excess of steroids such as the hormone cortisol or similar synthetic versions. This can occur either because:

  • the body produces too much cortisol hormone by itself (known as ‘endogenous’ Cushing’s syndrome) or
     
  • a person takes large amounts of steroid medication to treat conditions such as asthma, rheumatoid arthritis or eczema. This is known as ‘exogenous’ Cushing’s syndrome.

What causes Cushing’s syndrome?

Cortisol is a steroid hormone produced by the adrenal glands, which sit on top of the kidneys. The adrenal glands are stimulated by a pituitary hormone called adrenocorticotropic hormone to release cortisol into the bloodstream.

There are a number of causes of Cushing’s syndrome:

  1. Steroid medication taken to treat conditions such as asthma, rheumatoid arthritis or eczema.
     
  2. A tumour of the pituitary gland that produces too much adrenocorticotropic hormone. Excess adrenocorticotropic hormone due to a pituitary tumour is called Cushing’s disease and although this is quite rare, it is the commonest cause of endogenous Cushing’s syndrome.
     
  3. Overactivity of the adrenal gland (adrenal Cushing’s) causing excess cortisol production. This is very rare.
     
  4. Non-pituitary tumours that produce excess adrenocorticotropic hormone. These are often found in the lung and can be carcinoid tumours. The excessive production of adrenocorticotropic hormone from a non-pituitary tumour is often termed ‘ectopic adrenocorticotropic hormone production’ (ectopic meaning 'from the wrong place' – i.e. not from the pituitary gland). 

What are the signs and symptoms of Cushing’s syndrome?

Cushing’s syndrome is characterised by the following signs and symptoms:

  • central obesity (but thin arms and legs)
     
  • a round moon-like face
     
  • fat deposition above the collar bone and behind the neck
     
  • thin skin that bruises easily
     
  • muscle weakness, especially of the shoulder and thighs
     
  • high blood pressure
     
  • high blood sugar (glucose intolerance or diabetes mellitus)
     
  • stomach ulcers
     
  • thin bones (osteoporosis) and increased risk of fractures
     
  • increased rates of infection and poor wound healing
     
  • depression and other psychiatric problems
     
  • excess hair growth and irregular periods in women
     
  • reduced libido and erectile dysfunction in men.

How common is Cushing’s syndrome?

The most common form of Cushing’s syndrome is the exogenous form, i.e. due to the patient taking an excess of steroid medication. Endogenous Cushing’s syndrome is rarer and is estimated to affect 1 in 500,000 adults per year. Of these, 85% have pituitary-dependent Cushing’s syndrome, 10% have adrenal Cushing’s and 5% have ectopic adrenocorticotropic hormone production (from a non-pituitary tumour).  

Is Cushing’s syndrome inherited?

Cushing’s syndrome is not usually inherited, but in very rare cases can run in families.

How is Cushing’s syndrome diagnosed?

The first step in diagnosing Cushing’s syndrome is to look at current medication the patient is taking to rule out exogenous Cushing’s syndrome. Steroids can be found in prescription medications such as tablets, creams, ointments, inhalers, drops or sprays. Occasionally, steroids may be found as a contaminant in certain herbal preparations.

To diagnose endogenous Cushing’s syndrome, excessive cortisol levels can be measured in blood and urine samples taken over a 24-hour period. Usually, cortisol levels fall at night, but in patients with Cushing’s syndrome cortisol levels remain high.

The overnight dexamethasone suppression test is routinely used to screen for Cushing’s syndrome. In this test, the patient takes 1 mg of a synthetic steroid called dexamethasone at midnight then has a blood test for cortisol at 9 a.m. the next morning. In patients without Cushing’s syndrome, cortisol levels are reduced, but in patients with Cushing’s syndrome cortisol levels will remain raised. This screening test is then followed by a low dose dexamethasone suppression test to confirm the diagnosis.  

Once Cushing’s syndrome is confirmed, further blood tests may then be carried out, possibly as an inpatient, as well as specialised computerised tomography (CT) or magnetic resonance imaging (MRI) scans of the pituitary and adrenal glands. This will establish whether the excess cortisol is due to a problem with the adrenal glands or whether excess adrenocorticotropic hormone is driving the adrenals to produce too much cortisol.  

Inferior petrosal sinus sampling is often carried out to determine whether the source of the adrenocorticotropic hormone production is within the pituitary gland. This involves placing thin plastic tubes, under local anaesthetic, into a vein in the groin area. These are threaded into the blood vessels next to the pituitary gland with the aid of an X-ray machine and are used to take blood samples. The blood samples will help distinguish Cushing’s disease from ectopic adrenocorticotropic hormone production. 

A bone mineral density test may also be carried out to test for osteoporosis.

It may take some time before investigations are complete and Cushing’s syndrome is diagnosed. 

How is Cushing’s syndrome treated?

Exogenous Cushing’s syndrome is treated by gradually reducing the steroid drug dose under medical supervision, if this is possible. This must be done in conjunction with the specialist who prescribed the steroid drug. In some serious conditions, the steroids cannot be stopped. For some conditions, there are alternative drugs to steroids, but these might have their own side-effects. It is very important that the patient does not stop taking any steroid medication without discussing it with their doctor.

Depending on the cause, endogenous Cushing’s syndrome is treated by surgery, medication, or radiotherapy. The main goals of treatment are to bring cortisol levels back to normal, to reverse signs and symptoms and to maintain control in the long term.  

  • Pituitary tumours may be able to be removed by surgery through the nose leaving no visible scars. The surgery will be performed at a specialist neurosurgical hospital and results in a 60–80% success rate depending on a number of factors. See the article on Cushing’s disease for further information.
     
  • The adrenal glands can be removed laproscopically (through small cuts in the skin) at a specialist hospital. This is usually only carried out if pituitary surgery cannot be performed (or is not successful) and results in hypoadrenalism, which requires life-long steroid hormone replacement. Nelson’s syndrome is the term used to describe an enlargement of an adrenocorticotropic hormone-producing tumour in the pituitary gland, which can occur following surgical removal of both adrenal glands.

    Surgery to remove an adrenal gland is usually the best treatment option for adrenal Cushing’s syndrome when only one adrenal gland is affected; in this case there is usually no need for life-long steroid dependency.
     
  • Medication can be given to reduce the amount of cortisol produced by the adrenal glands. Drugs such as metyrapone or ketoconazole are given in tablet form, either for a short period to prepare patients for surgery, or long term if the patient is not fit for surgery.
     
  • Radiotherapy to the pituitary is used if surgery is not an option or has not been successful. This is an outpatient treatment and involves the patient receiving small daily doses of radiation for four to five weeks.

Are there any side-effects to the treatment?

After treatment, it is often necessary for the patient to take hydrocortisone tablets to replace the cortisol hormone, as the body has ‘forgotten’ how to make this vital hormone. Hydrocortisone tablets are taken two to three times a day until normal pituitary and adrenal function is restored. This could be for several months or patients may need to continue taking hydrocortisone for life.

If pituitary surgery or radiotherapy is carried out, the patient may develop deficiencies of other hormones which may need replacement (hypopituitarism). It may be necessary for the patient to take tablets for life to replace these essential pituitary hormones. 

Tablets taken to reduce cortisol levels can have side-effects on the liver and kidneys, so regular blood tests are carried out to make sure the patient is on the correct dose and that there are no serious problems.

What are the longer-term implications of Cushing’s syndrome?

Following successful treatment of Cushing’s syndrome, it may take between several weeks and a couple of years for the changes due to excessive cortisol production to return to normal and for the symptoms to disappear. Muscle and bone strength will improve, but some patients, particularly post-menopausal women, may need treatment for osteoporosis. Blood pressure and blood sugar should be closely monitored.

Patients may need to take hydrocortisone replacement tablets for life. Higher doses of hydrocortisone must be supplied for medical emergencies as the body is unable to make its own cortisol in response to stressful situations. Patients should also carry an intramuscular hydrocortisone injection in case of vomiting and a steroid card, and wear Medic-Alert jewellery.


Last reviewed: Jan 2015