Cushing’s syndrome


Cushing’s syndrome


Cushing's syndrome (hypercortisolism) is a collection of symptoms caused by very high levels of a hormone called cortisol in the body.

The symptoms of Cushing's syndrome include:

weight gain

thinning skin that bruises easily

reddish-purple stretch marks on the thighs, stomach, buttocks, arms, legs or breasts

fat deposits that develop in the face, causing it to become round

muscle or bone weakness 

decreased interest in sex (loss of libido)

What causes Cushing's syndrome?

Cushing's syndrome often develops as a side effect of treatment with corticosteroids. Corticosteroids are widely used to reduce inflammation and treat autoimmune conditions (where the immune system malfunctions and attacks healthy tissue).

People taking high doses of corticosteroids long-term often have a build-up of cortisol in their blood. This type of Cushing's syndrome is sometimes called iatrogenic Cushing's syndrome.

A less common cause of Cushing's syndrome is where a tumour (growth) develops inside one of the body's glands, causing it to produce an excessive amount of hormones. This is known as endogenous Cushing's syndrome.


Diagnosing Cushing's syndrome

Cushing's syndrome can be difficult to diagnose because the symptoms are similar to those of other more common conditions, such as an underactive thyroid gland and high blood pressure.

Your GP will need to know whether you've been taking medication, and you'll probably need to have a urine test, blood test, or saliva test to measure the levels of cortisol in your body.


Treating Cushing's syndrome

The main treatment for iatrogenic Cushing's syndrome is to decrease or withdraw the use of corticosteroids. However, this must be done gradually to avoid any unpleasant side effects.

For endogenous Cushing's syndrome, surgery to remove the tumour is usually recommended. If surgery is unsuccessful or it's not possible to remove the tumour safely, medication can be used to counter the effects of the high cortisol levels.

Although treatment is effective, it can take some time to bring the symptoms under control – any time from a few weeks to a few years in some cases.

Left untreated, Cushing's syndrome can cause high blood pressure, which increases the risk of heart attack and stroke.


Who's affected?

Cushing's syndrome is very rare, affecting around 1 in 50,000 people. Anyone can get it, although it tends to affect adults aged from 20 to 50 years. Women are three times more likely to develop the syndrome than men.

Symptoms of Cushing's syndrome 

The pattern of symptoms in Cushing's syndrome can be highly unpredictable.

In some cases, the symptoms can develop quickly and be very severe. In other cases, the symptoms can develop gradually and be much milder.

Weight gain and fat deposits

Weight gain is the most common symptom of Cushing's syndrome, particularly on the chest, stomach and face. It occurs because cortisol causes fat to be redistributed to these areas.

People with Cushing's syndrome tend to have:

slim arms and legs compared with their chest and stomach

fat deposits on the back of the neck and shoulders – this is known as a "buffalo hump"

a red, puffy, rounded face

Children who develop Cushing's syndrome tend to be obese and have slow growth rates.

Skin changes

Symptoms that affect the skin include:

thin skin that bruises easily – cortisol causes proteins in the skin to break down and tiny blood vessels to become weak

reddish-purple stretch marks on the thighs, stomach, buttocks, arms, legs or breasts – cortisol makes the skin fragile

spots on the face, chest or shoulders

darkened skin on the neck

swollen ankles caused by a build-up of fluid (oedema)

excessive sweating (hyperhidrosis)

bruises, cuts, scratches and insect bites can take a long time to heal

Bones and muscles

People with Cushing's syndrome often have muscle weakness in their hips, shoulders, arms and legs.

Too much cortisol can also cause the bones to become weakened or brittle (osteoporosis). This may lead to problems, including:


bone pain

a bone fracturing during normal activities, such as bending and lifting

loss of height

a curved spine (kyphosis)

Depression and mood

Depression is common in people with Cushing's syndrome. It's also common to feel unusually tired all the time, which can contribute to feelings of depression.

People with Cushing's syndrome may also experience rapid mood swings or have emotional reactions that may seem inappropriate, such as laughing or crying for no apparent reason.

Other symptoms

Other symptoms of Cushing's syndrome include:

kidney stones

high blood pressure (hypertension)

increased blood sugar levels

excessive facial or body hair (hirsutism) in women 

loss of libido (sex drive)

erectile dysfunction – an inability to get or maintain an erection

infertility in men

irregular periods or absent periods in women

Causes of Cushing's syndrome 

Most cases of Cushing's syndrome are related to long-term use of corticosteroid medication.

This is known as iatrogenic Cushing's syndrome.

Corticosteroids are used to:

reduce inflammation in the body – this can be useful for treating conditions such as asthma or atopic eczema

suppress the immune system – in conditions such as rheumatoid arthritis and lupus

Corticosteroids are available in a number of different forms, including tablets (oral corticosteroids), sprays and inhalers (inhaled corticosteroids), creams and lotions (topical corticosteroids), and injections.

To help prevent side effects, corticosteroids are usually prescribed at the lowest possible effective dose. However, in people with severe symptoms that fail to respond to other forms of treatment, the only effective alternative is to prescribe a long-term course of high-dose corticosteroids.

Corticosteroids contain a synthetic (man-made) version of the cortisol hormone. Prolonged use can lead to cortisol levels building up and triggering Cushing's syndrome. Misusing corticosteroids or taking more than the recommended dose also increases your risk of developing Cushing's syndrome.

The risk of developing Cushing's syndrome is higher in people who take corticosteroids tablets, but it can also affect those who misuse inhalers or corticosteroid creams.

Endogenous Cushing's syndrome

A much rarer type of Cushing's syndrome, known as endogenous Cushing's syndrome, is caused by the body producing more cortisol than it needs.

The most common reason for this is a tumour (an abnormal growth of cells) that develops in the pituitary gland.

The pituitary gland is a pea-sized gland in the brain. It produces a hormone called adrenocorticotropin hormone (ACTH) that stimulates the adrenal glands, which in turn release cortisol into the blood.

The tumour can disrupt the normal workings of your pituitary gland so it produces excessive amounts of ACTH. This causes the adrenal glands to produce too much cortisol.

Less commonly, a tumour develops inside one of the adrenal glands, which leads to Cushing's syndrome. Another less common cause is a tumour developing inside the lungs and producing the ACTH hormone, known as ectopic ACTH syndrome.

Tumours that develop inside the pituitary or adrenal gland are usually benign (non-cancerous). Other than the symptoms of Cushing's syndrome, they don't usually pose a serious threat to a person's health. Tumours that develop inside the lung can sometimes be cancerous. It's unclear why these tumours develop

Diagnosing Cushing's syndrome 

Diagnosing Cushing's syndrome can often be challenging, particularly when the symptoms are mild. It could be several months before a diagnosis is confirmed.

You may be referred for a number of different tests, as symptoms of Cushing's syndrome are similar to those of other more common conditions, such as:

an underactive thyroid gland

high blood pressure (hypertension)

Your GP will want to know whether you're taking any medication, as long-term use of corticosteroids is the main cause of Cushing's syndrome.

Tell your GP about all the medication you're taking, including tablets, creams and lotions, plus any natural remedies. Some natural remedies contain steroids.

Testing for cortisol

If Cushing's syndrome is suspected, the amount of cortisol in your body will be measured using one or more of the following tests:

urine test

blood test

saliva test

The level of cortisol in saliva normally drops to low levels overnight. However, people with Cushing's syndrome show high levels late in the evening and overnight, and may be asked to collect a sample of saliva at midnight. Normally, this test is done at home and delivered to hospital in the next few days.

Before taking a blood test, you may be given a medicine called dexamethasone in tablet form. If you're otherwise healthy, dexamethasone should decrease your cortisol levels. If your cortisol levels don't decrease, it could be caused by Cushing's syndrome.

None of the above tests are completely accurate or reliable, but if you have one or more abnormal results, you'll usually be referred to an endocrinologist (a doctor who specialises in treating hormonal conditions). They should be able to confirm or rule out a diagnosis of Cushing's syndrome.

Finding the underlying cause

After being diagnosed with Cushing's syndrome, it's important to establish what's causing it (unless you're currently taking corticosteroids). This will help determine your course of treatment.

The first stage is to find out whether Cushing's syndrome is being caused by high levels of the adrenocorticotropin hormone (ACTH) in your blood. This would suggest there's a tumour in your pituitary gland or, less commonly, in your lungs. Low levels of ACTH would suggest there's a tumour in one of your adrenal glands.

A suspected tumour can usually be confirmed by a magnetic resonance imaging (MRI) scan, which can produce detailed images of the pituitary gland. Occasionally, despite having an MRI scan, it can be difficult to determine exactly where the tumour is located. If this is the case, a further test, known as petrosal sinus sampling, may be recommended.

Petrosal sinus sampling

Petrosal sinus sampling involves a blood sample being taken from the veins of both your pituitary gland and your forearm. The level of ACTH in both samples will be compared:

if the level is higher in the pituitary vein, the cause is probably a tumour in your pituitary gland

if levels are similar, the cause is probably a tumour elsewhere – further scans, such as a CT scan of your chest, may be carried out to check the tissues of your lungs

It can take a considerable amount of time before a full diagnosis is made. Repeated X-rays and scans are sometimes required.

While waiting for the test results, your doctor may decide to treat your Cushing's syndrome with medication, such as metyrapone, to reduce the amount of cortisol. If this is the case, you'll need monitoring tests, and sometimes you may have to stay in hospital for a few days to adjust to the tablets.

DEXA scan

You may also have a special type of X-ray called a DEXA scan, which can be used to check for any weakening of your bones (osteoporosis).

Treating Cushing's syndrome 

Treatment for Cushing's syndrome depends on what's causing high levels of cortisol to accumulate in your body.

If your Cushing's syndrome is caused by the long-term use of corticosteroids (iatrogenic Cushing's syndrome), you'll need to gradually reduce your dosage to the lowest possible dose required to control the condition being treated.

If your Cushing's syndrome is caused by a tumour (endogenous Cushing's syndrome), the following treatment options are available:

cortisol-inhibiting medications



Reducing corticosteroid use

It's usually not safe to suddenly stop taking corticosteroids. If you've been taking corticosteroids for a long time, your body may stop producing natural steroids.

If you suddenly stop taking your medication, you may experience symptoms such as fatigue, vomiting and diarrhoea. You may also need to continue taking your medication until the symptoms of the condition being treated are under control.

If you've only been taking corticosteroids for less than two weeks, it should be possible to safely stop the dose straight away.

There's no "one size fits all" plan for withdrawing treatment with corticosteroids. However, for most people, a gradual reduction is recommended. A blood test can be used a bit later to tell if your body's producing natural steroids.

It's only safe to stop taking steroids completely once your body is producing them naturally. This can take from a few months to more than a year. During this time you may need treatment for some of the symptoms of Cushing's syndrome, such as medication to lower your blood pressure.

Cortisol-inhibiting medications

Cortisol-inhibiting medications are designed to block the adverse effects of cortisol. They tend to be used short term leading up to surgery, or after surgery or radiotherapy, to help make these treatments more effective.

Occasionally, cortisol-inhibiting medications are used on a long-term basis in people unwilling or unable to have surgery. Ketoconazole and metyrapone are two widely used cortisol-inhibiting medications.

Ketoconazole isn't licensed for the treatment of Cushing's syndrome. This means the manufacturers designed and tested the medication for treating another condition (fungal infection) and it was subsequently found to also be useful for treating Cushing's syndrome.



Surgery may be needed to remove a tumour in the pituitary or adrenal glands. Removing a tumour from the lungs is much more challenging and may not be possible.

Pituitary gland removal

Surgery to remove a tumour in the pituitary gland is known as transsphenoidal adenoectomy. Under general anaesthetic, the surgeon removes the pituitary tumour either through your nostril or an opening made in your upper lip.

This type of surgery has a good track record of success. More than 80% of cases where the pituitary tumour is 10mm or smaller are cured. For larger tumours, the cure rate is around 50%. Sometimes a second surgical procedure is recommended if the first operation wasn't successful.

Adrenal gland removal

In most cases, only one adrenal gland will need to be removed. To do this, laparoscopic (keyhole) surgery is usually used. The surgeon makes a small incision in your abdomen and passes tiny instruments through it to remove your adrenal gland.

The advantage of keyhole surgery is that you'll feel less pain after the operation and have minimal scarring. Laparoscopic surgery has a good record of success, with more than 65% of people's symptoms being completely cured.

In more difficult or complex cases, removing both of your adrenal glands may be recommended so they're unable to produce any cortisol. This may be needed if your Cushing's syndrome symptoms are difficult to control in other ways and are putting your long-term health at risk. For example, this could be if you have poorly controlled high blood pressure (hypertension).

Lung tumour

If the tumour is located deep inside your lung, it may not be possible to destroy or remove it safely without seriously damaging the lung.

An alternative approach may be recommended, such as using cortisol-inhibiting medication or completely removing the adrenal glands to stop the production of cortisol.


Radiotherapy may be recommended if pituitary gland surgery doesn't achieve a cure or if you're unable to have surgery. It involves using high-energy X-rays to shrink the tumour and stop it producing adrenocorticotropin hormones (ACTH).

Normal radiotherapy is delivered daily in small doses over a period of five weeks. This helps to reduce damage to other areas of the brain.

However, a type of radiotherapy known as stereotactic radiosurgery (SRS) is increasingly being used to treat pituitary tumours. This uses a series of movable frames to hold your head in a precise position. A computer is then used to send energy rays to the exact location of the pituitary tumour.

The precise focusing of SRS is thought to minimise the chances of other parts of your brain being accidentally damaged. The whole radiation dose is delivered in just one session. As the procedure is only available at a number of specialised centres, it's likely you'll have to travel to receive treatment.

Both types of radiotherapy have advantages and disadvantages. Both have a good chance of curing Cushing's syndrome, but their effects may be slow and take months or years to reach full effect.

Complications of surgery

Complications can sometimes develop after surgery for Cushing's syndrome. Pituitary and adrenal operations carry a small risk of infection, bleeding, or anaesthetic complications.

Low cortisol level after surgery

Successful treatment to remove a pituitary or adrenal tumour leaves the body with abnormally low cortisol levels.

Most people need to take two to three tablets of replacement hydrocortisone a day. Treatment can be stopped if your glands recover their normal function after a few months, but it may be needed for several years.

If you have both of your adrenal glands removed, you'll permanently lose the ability to make cortisol. This requires long-term hydrocortisone replacement.

It may take a while to find the right dose of hydrocortisone, but most people tolerate the treatment well.

Loss of other pituitary hormonal function

The surgeon will try to save as much of your pituitary or adrenal gland as possible so they can still produce hormones. However, in some cases this may not possible, particularly if you have a large tumour.

Radiotherapy of any kind also increases your risk of losing normal hormonal function. If you lose normal hormonal function, you'll need to take man-made (synthetic) hormones, which are given as tablets or self-administered injections. 

The pituitary gland controls production of cortisol, thyroid hormone, growth hormone, testosterone (in men), oestrogen (in women) and vasopressin (which controls water balance). After treatment for Cushing's syndrome, some people need some or all of these hormones replaced.

Nelson's syndrome

Nelson's syndrome is very rare. It's a condition that sometimes develops after an operation to remove both adrenal glands.

Nelson's syndrome is a tumour inside your pituitary gland that grows fairly rapidly over a period of month. The symptoms include:

darkening of your skin


vision problems, such as partial vision loss or double vision

Treatment for Nelson's syndrome may involve surgery to remove the tumour, and often radiotherapy. Sometimes a tablet form of chemotherapy is used called temozolomide.

Cushing's syndrome