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 due to deposits of fat developing there
• decreased interest in sex
• 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.

Read more about the causes of Cushing’s syndrome.

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.

Read more about the treatment of Cushing’s syndrome.

Outlook

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 or stroke, both of which are serious and can be fatal.

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, known as a 'buffalo hump'
• 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. See the A-Z about Depression for more information about the condition.

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.

It is very important to rule out other disorders before Cushing's syndrome is diagnosed, so you can be properly treated.

Your GP can carry out an initial examination, but a full investigation by an endocrinologist (specialist in hormone problems) is necessary. A diagnosis will be based on your medical history, an examination, laboratory tests and scans.

Tests for Cushing's syndrome

The tests are done in hospital and include:

• Urine samples. These are collected over 24 hours and tested for cortisol levels. If you have Cushing's syndrome, the cortisol levels will be high throughout the day.
• Blood samples. These are also collected over a 24-hour period and tested for the levels of cortisol. Normally, cortisol levels fall at night, but in Cushing's syndrome they remain high.
• Low-dose dexamethasone supression test. A steroid tablet called dexamethasone is taken every six hours for two days. Urine is collected before the tablet is given and throughout the two days. Low-dose dexamethasone normally stops cortisol being produced. A cortisol level that does not drop indicates Cushing's syndrome.

Finding out the cause of Cushing's syndrome

Once you have been diagnosed with Cushing's syndrome, you will have further tests to determine what is causing the increased levels of cortisol.

• Corticotropin-releasing hormone (CRH) stimulation test. A CRH injection is given. If the levels of adrenocorticotropin hormone (ACTH) and cortisol in the blood rise, the cause is probably a tumour in the pituitary gland. If they do not rise, the cause is probably a tumour in the adrenal gland or elsewhere in the body.
• High-dose dexamethasone supression test. This is the same as the low-dose test (see above), but a higher dose of dexamethasone is given. If there is a tumour in the pituitary gland, a high dose usually lowers blood cortisol levels, but not if the tumour is elsewhere.
• Scans. You may have a computerised tomography (CT) or magnetic resonance imaging (MRI) scan of the pituitary or adrenal glands. This is used to detect any tumour that may be present. However, the results are not always clear and can sometimes fail to detect a very small tumour.
• Petrosal sinus sampling. A sample of blood is taken from the veins coming from the pituitary gland (the petrosal sinuses). The level of ACTH in this sample is measured and compared with the ACTH level in blood taken from your forearm. 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 the body.

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

Your doctor may decide to treat you in the meantime with drugs such as metyrapone to reduce the amount of cortisol (see Treatment, above). If this is the case, then you will have to stay in hospital for a few days so you can be monitored while taking the tablets.

You may also need a bone mineral density test to check for osteoporosis.

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

Corticosteroids

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

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.

Radiotherapy

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.