Cushing's syndrome

Cushing’s syndrome is a term used to describe a collection of symptoms caused by elevated levels of a hormone identified as cortisol in the blood. Cortisol is a form of glucocorticoid hormone and is made by the adrenal glands, which are small glands found higher than the kidneys; each person has two adrenal glands.

Glucocorticoids are steroid hormones. Cortisol is the main glucocorticoid hormone and has several important responsibilities in the body, including:

• Regulating blood pressure.
• Controlling the body’s reactions to stress.
• Regulating the immune system.
• Balancing the effect of insulin, important in the regulation of blood sugar levels.

What causes Cushing’s syndrome?

Corticosteroid medication

Cushing’s syndrome is often caused by long-term corticosteroid medication (known as iatrogenic or exogenous Cushing’s syndrome). Corticosteroids help to reduce swelling and suppress the immune system in patients with autoimmune disorders. There are many different types of corticosteroid, available in tablet form, as topical creams and lotions, as injections and as inhalers. Corticosteroids are usually prescribed in relatively low doses as they are known to cause side-effects; however, if a patient fails to respond to other treatments a long term dose or a higher dose may be required. Corticosteroids contain cortisol so the levels of the cortisol may increase over time, which can contribute to Cushing’s syndrome. The risk of developing Cushing’s syndrome is higher in people who take oral corticosteroids than those who use the creams, lotions and sprays.

Endogenous Cushing’s syndrome

The body can produce excessive cortisol in rare cases, which is termed as endogenous Cushing’s syndrome. The most widespread cause of endogenous Cushing’s syndrome is a tumour in the pituitary gland (this accounts for 70% of endogenous Cushing’s syndrome cases). The pituitary gland is found at the base of the brain and is responsible for producing a number of hormones that have a variety of important functions in the body. A tumour in the pituitary gland affects cortisol levels because it can increase the presence of a hormone called ACTH (adrenocorticotropin), which the pituitary gland produces. ACTH kindles the adrenal glands to release more cortisol raising levels in the blood. Women are five times more likely than men to have endogenous Cushing’s syndrome.

It is rare that Cushing’s syndrome should be the effect of the development of a tumour in the adrenal glands. In fewer than 1 in 10 cases a tumour develops in the lungs and produces ACTH hormone, causing endogenous Cushing’s syndrome. This is recognised as ectopic ACTH syndrome and is more common in men than women.

In the mainstream of cases tumours in the adrenal glands and pituitary gland are benign, meaning that they are not cancerous.

Symptoms of Cushing’s disease

Symptoms can develop gradually as the levels of cortisol in the blood are likely to increase over a long period of time. They include:

• Obesity and weight gain, especially around the waist.
• Increased redness in the face.
• Increased roundness in the face.
• Weakened muscles.
• Thinning skin.
• Bruising easily.
• Decreased libido.
• Stretch marks.
• Aches and pains, usually in the back.
• Mood swings.
• Diabetes.
• Increased facial and body hair in women.
• High blood pressure.
• Reduced fertility.
• Erectile dysfunction in men.
• Delayed growth and development in children.
• Osteoporosis (thinning or weakening of the bones).

Many people develop a number of the symptoms listed above, but it is unusual to develop them all.

How is the syndrome diagnosed?

Most symptoms caused by Cushing’s syndrome are similar to a number of other health conditions, so it can be difficult to make a diagnosis. Commonly, conditions like hypertension (high blood pressure) and diabetes are diagnosed instead of Cushing’s syndrome.

When you see your GP they will ask you about your medical history, your symptoms and whether you are taking any medication. As the majority of cases are linked to corticosteroid medication, your GP will ask if you are taking corticosteroids or have taken them in the past. If your GP suspects that you have Cushing’s syndrome you will be referred for tests.

Tests used to diagnose Cushing’s syndrome include:

• Blood test.
• Urine test.
• Saliva test.

The aim of the tests is to measure the levels of cortisol in the body. You will be asked to collect urine samples over a twenty-four hour period, which will be sent to the laboratory for analysis. You may also have a blood test after taking a form of medication called dexamethasone, which is designed to stem cortisol production. If the test results are still high, this indicates the presence of Cushing’s syndrome. The saliva test is usually carried out in the middle of the night, as cortisol levels should be low when you are asleep and so high levels will indicate Cushing’s syndrome.

Further tests

If Cushing’s syndrome is diagnosed other tests may be needed to determine the cause of the condition. These tests will gauge the level of ACTH in the blood. If the results are abnormally low this may indicate a tumour in the adrenal glands, while a high result from blood in the pituitary vein may indicate a pituitary tumour.

A CT scan is usually used to corroborate the diagnosis of a tumour. The scan images can confirm the presence of the tumour, as well as showing the size and exact location. A bone density scan may also be needed to monitor for signs of osteoporosis.

Treatment for Cushing’s syndrome

Iatrogenic Cushing’s syndrome

Treatment for Cushing’s syndrome depends on the underlying cause. Most of the time the condition happens because of corticosteroid medication (iatrogenic Cushing’s syndrome) and treatment involves reducing the dosage of corticosteroids. It is vital that the amount of corticosteroids be reduced gradually over a period of time, as stopping suddenly can be harmful resulting in the following symptoms:

• Fatigue.
• Dizziness.
• Sickness.
• Nausea.
• Diarrhoea.

Endogenous Cushing’s syndrome

Medication

In the case of endogenous Cushing’s syndrome, there are various treatment options. Medication is one such method and is used to prohibit the adverse effects of cortisol. These medicines, known as cortisol-inhibiting medications, are usually used on a short-term basis before surgery.

Surgery

Surgery is often undertaken when Cushing’s syndrome is the result of tumours in the pituitary or adrenal glands. The procedure to remove a tumour from the pituitary gland is performed under general anaesthetic. The surgeon accesses the gland either through an incision behind the upper lip or by way of a slit in the nostril. The aim is to take away the tumour without causing any damage to the pituitary gland. In the case of a tumour on the adrenal gland, surgery will usually be performed to remove one of the glands via keyhole surgery (known as laparoscopy).

As with all surgical procedures there is a risk of complications. These include:

• Impaired hormone function: if this is the case the patient will be told to take hormone replacement medication.
• Nelson’s syndrome: this causes a tumour to grow quickly in the pituitary gland. It is most frequent in patients who have undergone adrenal gland removal due to other treatments failing.

Radiotherapy

Radiotherapy may be required if surgery isn’t viable or has been unsuccessful. A relatively new form of radiotherapy called stereotactic radiosurgery (also known as SRS) is becoming an increasingly common treatment for pituitary tumours. This form of radiotherapy is more accurate and reduces the risk of damage to other areas of the brain.