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Cushing's syndrome

Page last reviewed: 13/07/2011

Cushing's syndrome is a term that's used to describe a wide range of symptoms that can be triggered if a person has very high levels of a hormone called cortisol in their blood.

The most common symptoms of Cushing's syndrome are:

  • weight gain
  • rounding of the face
  • thinning of the skin
  • thinning of the skin

What causes Cushing's syndrome?

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

People who take high doses of corticosteroids on a long-term basis can sometimes experience a build-up of cortisol in their blood. This form of Cushing's syndrome is sometimes called iatrogenic Cushing's syndrome.

A much less common cause of Cushing's syndrome is where a tumour develops inside one of the glands in the body, causing the gland to produce an excessive amount of hormones. This form of Cushing's syndrome is sometimes called endogenous Cushing's syndrome.

Women are five times more likely to develop endogenous Cushing's syndrome than men, with most cases affecting people who are 25 to 40 years old.

Treating Cushing's syndrome

The main treatment option for people with iatrogenic Cushing's syndrome is to try to lower or withdraw their corticosteroid dosage. This has to be done gradually because suddenly stopping a course of corticosteroids can cause unpleasant side effects.

The main treatment option for endogenous Cushing's syndrome is to surgically remove the tumour. If surgery proves unsuccessful, or if the tumour can't be safely removed, medication can be used to counter the effects of the high cortisol levels.


With treatment, the outlook for people with Cushing's syndrome is usually good. However, the time it takes to bring the symptoms under control can vary widely from a few weeks to a couple of years.

If Cushing's syndrome is left untreated, the outlook is much less favourable because the excessive levels of cortisol can cause high blood pressure (hypertension). High blood pressure increases a person's risk of having a heart attack, stroke, or both of which are serious and can be fatal.

Page last reviewed: 13/07/2011

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

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

People with Cushing's syndrome tend to have:

  • very slim arms and legs compared with their chest and stomach
  • deposits of fat on the back of the neck and shoulders,
  • a red, puffy and rounded face

Skin changes

Symptoms that affect the skin include:

  • thin skin that bruises easily because 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 because cortisol makes the skin fragile
  • spots on the face, chest or shoulders
  • darkened skin on the neck
  • swelling of the legs due to a build-up of fluid (oedema)
  • heavy sweating
  • bruises, cuts, scratches and insect bites can take a long time to heal

Symptoms in men

Additional symptoms in men include:

  • decreased interest in sex
  • erectile dysfunction- not being able to get or maintain an erection
  • infertility


Symptoms in women

Additional symptoms in women include:

  • excessive facial and/or body hair (hirsutism)
  • irregular periods or absent periods

Symptoms in children

Children who develop Cushing's syndrome may experience delayed or missing growth.

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 brittle bones (osteoporosis). This may lead to an affected bone breaking when doing normal, every day activities, such as bending and lifting.

Mental health

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

Many people with Cushing's syndrome will also experience rapid mood swings and have emotional reactions that 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)
  • an increase in blood sugar levels

These types of symptoms often go unnoticed and are only detected during medical scans and tests.

Page last reviewed: 13/07/2011

Iatrogenic Cushing's syndrome

Most cases of Cushing's syndrome are related to the use of corticosteroid medication.

Corticosteroids have two main uses. They:

  • reduce inflammation in the body; this can be useful for treating conditions such as asthma, and skin conditions such as atopic eczema
  • suppress the immune system, which can be useful for treating conditions, such as rheumatoid arthritis and lupus, where the immune system mistakenly attacks healthy tissue

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 version of the cortisol hormone, so cortisol levels can build up over time, triggering Cushing's syndrome. People who misuse corticosteroids or take a higher than recommended dose are also at risk of developing Cushing's syndrome.

The risk of developing Cushing's syndrome is higher in people who take oral corticosteroids, although the condition can also affect those who misuse inhaled or topical corticosteroids.

Endogenous Cushing's syndrome

Endogenous Cushing's syndrome is much less common than iatrogenic Cushing's syndrome. It's caused by your body producing more cortisol than you actually need.

The most common cause of endogenous Cushing's syndrome is a tumour (an abnormal growth of cells) which develops in the pituitary gland.

The pituitary gland is a pea-sized gland in your brain. It doesn't produce cortisol, it produces another hormone called adrenocorticotropin hormone (ACTH). ACTH stimulates two small organs that lie above the kidneys, known as the adrenal glands. The adrenal glands release cortisol into the blood.

The tumour can disrupt the normal workings of your pituitary gland so that it produces excessive levels of ACTH, which cause the adrenal glands to produce too much cortisol.

This type of endogenous Cushing's syndrome is known as Cushing's disease. It's responsible for 70% of all endogenous cases and it's five times more likely to develop in women than in men.

A less common cause of endogenous Cushing's syndrome is where a tumour develops inside one of the adrenal glands. This accounts for around 1 in 10 cases of the condition.

Another less common cause is known as ectopic ACTH syndrome. This is where a tumour develops inside the lung and starts to produce the ACTH hormone. This type of Cushing's syndrome is more common in men.

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

Benign refers to a condition that should not become life-threatening. If a tumour is described as benign, it is not cancerous.
Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.
The brain controls thought, memory and emotion. It sends messages to the body controlling movement, speech and the senses.
Dose is a measured quantity of a medicine to be taken at any one time.
Immune system
This is the body's defence system, which helps protect it from disease, bacteria and viruses.
Insulin is a hormone released by the pancreas which helps control blood sugar levels.
The kidneys are a pair of bean-shaped organs which are located at the back of the abdomen. They remove waste and extra fluid from the blood and pass them out of the body as urine.
Malignant is a term used to describe a life-threatening or worsening condition. In the case of tumours, malignant means cancerous.
Pituitary gland
The pituitary gland is a pea-sized gland which hangs below the brain. It produces hormones.

Page last reviewed: 13/07/2011

Making a successful diagnosis of Cushing's syndrome can often be challenging, particularly when the symptoms are mild.

As Cushing's syndrome shares symptoms with other, more common conditions, such as an underactive thyroid gland and high blood pressure (hypertension), you may be referred for a number of different tests. As a result, it could take several months before a diagnosis is confirmed.

Medication history

As corticosteroid use is the leading cause of Cushing's syndrome, your GP will ask you if you have been taking any medication.

You should give your GP a complete list of all the medication you're taking, including tablets, creams and lotions, plus any natural remedies. This is because some natural remedies contain steroids.

Testing for cortisol

You'll probably need to have one or more of the following tests, which can be used to measure the levels of cortisol in your body:

  • urine test
  • blood test
  • saliva test - this is most accurate when it's carried out in the middle of the night, so you may be asked to stay in hospital overnight

You may also be given a medication called dexamethasone before being asked to take a blood test. If you're otherwise healthy, taking dexamethasone should decrease your cortisol levels. If your cortisol levels are unaffected, it could be due to Cushing's syndrome.

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

Determining the underlying cause

Once a diagnosis of Cushing's syndrome has been confirmed, it will be necessary to determine the underlying cause (unless you're currently taking corticosteroids because this will be the cause), to decide on your course of treatment.

The first stage is to determine whether your Cushing's syndrome is the result of high levels of the adrenocorticotropin hormone (ACTH) in your blood. If so, this would suggest that there's a tumour in your pituitary gland or, less commonly, your lungs.

Low levels of ACTH would suggest that there's a tumour in one of your adrenal glands.

A suspected tumour can usually be confirmed by taking a computer tomography (CT) or MRI scan of the location. During a CT/MRI scan, the scanner takes a series of pictures and a computer assembles them into a detailed image of different parts of the body.

Occasionally, despite having a CT/MRI scan, it can be difficult to determine where the tumour is located. In such circumstances, a further test, known as petrosal sinus sampling, may be recommended.

A sample of blood is taken from the veins of your pituitary gland and your forearm and the level of ACTH in both samples is 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 in your lungs. Further X-rays and CT/MRI scans of your chest may be carried out to check the tissues of your lungs.

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

In the meantime, 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 have to stay in hospital for a few days so that you can be monitored while taking the tablets.

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

Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.
Blood test
A sample of blood is taken from a vein using a needle and is examined in a laboratory.
Dose is a measured quantity of a medicine to be taken at any one time.
Lungs are a pair of organs in the chest that control breathing. They remove carbon dioxide from the blood and replace it with oxygen.
Magnetic resonance imaging (MRI)
MRI uses magnets and radio waves to take detailed pictures of inside the body.
Pituitary gland
The pituitary gland is a pea-sized gland that hangs below the brain and produces hormones.
An X-ray is a painless way of producing pictures of inside the body using radiation.

Page last reviewed: 13/07/2011

The treatment of Cushing's syndrome will depend on the cause of the high levels of cortisol. If you have iatrogenic Cushing's syndrome that's caused by taking corticosteroids, you'll need to gradually reduce then stop your dose of corticosteroid medication.

If you have endogenous Cushing's syndrome that's caused by tumours, you have the following treatment options:

  • cortisol-inhibiting medications
  • surgery
  • radiotherapy


If you've only been taking corticosteroids for a few days, it may be possible to safely stop the dose straight away. However, most people with Cushing's syndrome have been taking high-dose corticosteroids for some time so it's not safe to stop the dose.

This is because if you've been taking corticosteroids for a long time, your body may stop producing natural steroids. So if you suddenly stop taking your medication you may have symptoms such as:

  • fatigue
  • weight loss
  • feeling sick
  • dizziness
  • being sick
  • diarrhoea

Another factor is the condition for which you've been prescribed your medication in the first place. In some cases, there may be an effective non-steroidal treatment. However, if this is not the case you may be advised to continue taking corticosteroids until the symptoms of that condition are under control.

There's no 'one size fits all' plan for withdrawing treatment with corticosteroids. However, the following steps are recommended for most people:

  • Reduce the dosage from a high dose to a medium dose or a medium-high dose.
  • Then switch to an even lower dose or, alternatively, only take your medication every other day.
  • Then, after a number of weeks or months, have a blood test to see whether your body is now producing natural steroids.

If, after the steps described above, your body is producing natural steroids, it should be safe to withdraw treatment. If your body isn't producing natural steroids, continuing a low-dose treatment may be recommended for another four to six weeks before being tested again.

The time that it takes for someone to safely withdraw from taking corticosteroids can range from a few months to more than a year. You may need additional treatment during this time to compensate 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 only on a short-term basis as a preparation for surgery. Sometimes they're used for a short time after surgery or radiotherapy in order to make these types of treatment more effective.

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

Side effects of ketoconazole include:

  • drowsiness
  • headaches
  • feeling sick
  • irregular periods
  • lack of interest in sex
  • swelling of breasts in men

Side effects of metyrapone include:

  • high blood pressure (hypertension)
  • acne
  • excessive hair growth on your face and skin

As ketoconazole can cause breast growth in men, metyrapone is usually recommended. Similarly, because metyrapone can cause excessive hair growth, women are usually advised to take ketoconazole.


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

Pituitary surgery

Under general anaesthetic, the surgeon will remove your pituitary tumour through your nostril or an opening that's made behind your upper lip, just above your front teeth.

This approach allows the surgeon to reach your pituitary gland without having to operate on the main part of your head. This reduces the risk of complications, such as infection.

This type of surgery has a good track record of success. Around four out of five people's symptoms are completely cured.

Adrenal gland surgery

In most cases, only one of your adrenal glands will need to be removed. This is usually done using laparoscopic (keyhole) surgery, in which the surgeon makes a small incision in your abdomen and passes tiny instruments through the incision to remove the adrenal gland. The advantage of this approach is that you'll feel less pain after surgery and have minimal scarring.

This type of surgery also has a good record of success. Two out of three people's symptoms are completely cured.

The lungs

In many cases, the tumour is located deep inside the lung so it's not possible to safely remove or destroy it without seriously damaging the lungs. An alternative approach is to use cortisol-inhibiting medication or completely remove the adrenal glands, which will stop the production of cortisol.


If pituitary surgery proves unsuccessful, radiotherapy is an additional treatment where high-energy waves can be used to shrink the tumour.

A type of radiotherapy known as stereotactic radiosurgery (SRS) is increasingly being used to treat pituitary tumours. SRS involves using a series of movable frames to hold your head in a precise location. Then a computer sends energy rays to the exact location of the pituitary tumour.

This new approach minimises the chances of accidental damage to other parts of the brain. It usually takes just one session to perform.

SRS is only available at a number of specialised centres so it's likely that you'll have to travel from your home to receive treatment. There may also be a waiting list until treatment becomes available. The results of SRS are good, with 3 out of 4 people experiencing a complete cure from their symptoms.

Treatment failure

If pituitary surgery, adrenal gland surgery and/or radiotherapy fail to achieve a cure, it may be recommended that both of your adrenal glands be surgically removed so that they can no longer produce cortisol.

This treatment option may be highly recommended if your symptoms of Cushing's syndrome put your long-term health at risk, such as poorly controlled high blood pressure.

Complications of surgery

Loss of hormonal function

The surgeon will try to save as much pituitary or adrenal gland as possible to preserve their normal functions of producing hormones. However, in some cases, this is not possible, particularly if a tumour is quite large.

People who have had their entire adrenal gland removed will lose normal hormonal function. Those undergoing radiotherapy have a significant risk of losing normal hormonal function.

If you lose normal hormonal function, you'll have to take synthetic versions of the hormones that the affected glands used to make. This is sometimes referred to as hydrocortisone replacement therapy (not to be confused with hormone replacement therapy, which is used to treat the symptoms of the menopause).

Hydrocortisone comes in tablet form. Most people need to take one or two tablets a day. In some cases, your glands may recover normal function after a few months, so treatment can be stopped. Other people may need to take hydrocortisone for the rest of their life.

Most people tolerate hydrocortisone well, but it can take some time to work out what's the most appropriate dose for you. During this time you may have some Cushing syndrome-like side effects, such as weight gain and thinning of your skin.

Nelson's syndrome

Nelson's syndrome is a relatively common complication that occurs in people who have had both of their adrenal glands removed because they were unresponsive to surgery or radiotherapy.

Nelson's syndrome is where a rapidly growing tumour develops inside your pituitary gland. The symptoms include:

  • darkening of your skin
  • headaches
  • vision disturbances, such as partial loss of vision or double vision

Nelson's syndrome is poorly understood, both in terms of what causes it and how common it is. One study carried out several years ago found that one in four people who had both adrenal glands removed went on to develop Nelson's syndrome. However, the figure is likely to be lower today due to improvements in the treatment of Cushing's syndrome.

The treatment recommended for Nelson's syndrome is to surgically remove the tumour. This may be followed by an additional course of radiotherapy as discussed above.

Benign refers to a condition that should not become life-threatening. In relation to tumours, benign means not cancerous.
Chemotherapy is a treatment of an illness or disease using a chemical substance, such as in the treatment of cancer.
Dose is a measured quantity of a medicine to be taken at any one time.
Lungs are a pair of organs in the chest that control breathing. They remove carbon dioxide from the blood and replace it with oxygen.
The term malignant describes a life-threatening or worsening condition. In the case of tumours, malignant means cancerous.
Pituitary gland
The pituitary gland is a pea-sized gland which hangs below the brain and produces hormones.
Radiotherapy is a treatment which uses X-rays to treat disease, especially cancer.

Content provided by NHS Choices www.nhs.uk and adapted for Ireland by the Health A-Z.

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