Cushing's Syndrome

cushings syndrome

Cushing's syndrome is caused by too high a level of glucocorticoid in the body. Glucocorticoids are a class of steroid hormones. Cushing's syndrome develops when the level of a glucocorticoid in your body is too high over a long period of time. Too much glucocorticoid can occur from an exogenous or endogenous source:

Exogenous glucocorticoids

This means you take a glucocorticoid medicine regularly. These medicines are commonly called steroid medicines. Prednisolone is the most commonly prescribed steroid medicine. Steroid medicines are sometimes used to treat various conditions such as some types of arthritis, and for some cancers. Long-term treatment with a steroid medicine that can cause Cushing's syndrome. This is the most common cause.

Endogenous glucocorticoids

This means glucocorticoids made by your body. Cushing's syndrome can develop when your body makes too much of a hormone called cortisol (a main glucocorticoid). This  is a very rare cause. Most cases are in people aged between 20 and 50. Women are five times more commonly affected than men.

What is cortisol and what does it do?

Cortisol is classed as a glucocorticoid hormone which is made by the adrenal glands.. The amount of cortisol which is made in the adrenal glands is controlled by another hormone called adrenocorticotropic hormone (ACTH) ,made in the pituitary gland. You have two small adrenal glands which lie just above each kidney. Cortisol is vital for life. It has several functions including:

Helping to regulate blood pressure.
Helping to regulate the immune system.
Helping to balance the effect of insulin to keep the blood sugar level normal.
Helping the body to respond to stress.
How is the level of cortisol normally controlled?

The level of cortisol needs to be just right. Too much or too little can cause problems. The amount of cortisol which is made in the adrenal glands is controlled by another hormone called adrenocorticotropic hormone (ACTH) - and sometimes just called corticotropin. ACTH is made in the pituitary gland in brain.

What causes abnormal levels of cortisol?

There are a number of causes. These include the following:

Pituitary adenoma,a small, benign (non-cancerous) tumour in the pituitary - Cushing's disease
Adrenal problems
Adrenal hyperplasia - which means there is increased number and growth of the cells , tumour(benign or malignant) in the adrenal glands.
Other causes of too much ACTH ('ectopic ACTH')
Some types of lung cancer.
A variety of tumours can make ACTH, some malignant, and some benign.
Steroid medicines
 Long-term treatment with steroids can cause symptoms and problems similar to Cushing's syndrome.

Other causes

Some people who drink a lot of alcohol make too much cortisol. The cortisol level goes back to normal if drinking alcohol stops.
Some people with severe depression make too much cortisol.
What are the symptoms of Cushing's syndrome?
Obesity - with fat around the main body area (trunk) rather than the arms and legs. The arms and legs can become quite thin compared with the obese body.
Facial puffiness, and the face often looks redder than usual.
Facial hair in women.
High blood pressure.
Muscle weakness. Specially muscles around the thigh, pelvis, shoulders and upper arms
Thin skin which bruises easily.
Purple/pink stretch marks (striae) may appear - similar to those seen on some pregnant women.
Aches and pains - particularly backache.
Mood swings - such as being more irritable, depressed, or anxious than usual.
Lack of sex drive (libido).
Periods may become irregular, or stop, in women.
Osteoporosis ,You may fracture a bone more easily than usual.
Swelling on feet
Excess thirst.
Increased susceptibility to infections.
Affected children tend to be obese, but grow slowly so are short for their age.

What tests are needed?

Tests to confirm the high level of cortisol

The level of cortisol normally varies throughout the day. So, a simple blood test is not good enough to diagnose Cushing's syndrome.
A test to measure the amount of cortisol that you pass in your urine. You need to collect all the urine that you pass over 24 hours into a plastic container. This is sent to the laboratory to measure the cortisol.
In addition, or as an alternative, a blood test may be arranged after you take a medicine called dexamethasone. This medicine normally suppresses the amount of cortisol that you make. A blood cortisol level which is high after taking this medicine helps to confirm Cushing's syndrome.
A night-time blood test or saliva test to measure the level of cortisol. The level of cortisol should be low after you go to sleep, and a high level is abnormal.

Tests to find the cause of the high cortisol

Once it is confirmed that you are making too much cortisol, you will need further tests to find out what is causing the high level. Blood tests which measure cortisol and other hormones may help to locate the cause. This may involve taking blood from unusual sites of the body. You may also need a scan of the pituitary, adrenal glands, or other parts of the body. The tests are often quite complex.

What is the treatment of Cushing's syndrome?

The treatment options depend on what is causing the high level of cortisol.

Surgical treatment for a pituitary adenoma

The surgeon can get to the pituitary gland through a small cut behind the upper lip, just above the front teeth (or sometimes from inside a nostril). The instruments are passed through the base of the skull - the sphenoid bone. So, this operation is called 'trans-sphenoidal surgery', and is done under general anaesthetic. The aim is to remove the adenoma, but to leave the rest of the pituitary gland intact. Removing the adenoma causes the level of cortisol in your body to go from high to almost zero. So, following surgery you need to take a medicine called hydrocortisone (similar to cortisol) for several months before your pituitary gets back to normal. It also takes several months for your body to readjust, and for symptoms gradually to improve.

The operation is successful in about 8 in 10 cases. Your surgeon will advise on the possible complications which sometimes occur.

Where pituitary surgery is not possible, or declined, or has failed, other treatments may be considered:

Radiotherapy to the pituitary gland can destroy the pituitary adenoma. This has a good chance of success, but may take months or years to take effect. Also, the radiotherapy may damage the normal pituitary cells, and may cause low levels of other hormones made by the pituitary gland. However, replacement hormone therapy can usually be taken if this occurs.

Treatments for other causes of Cushing's syndrome

The treatment options depend on the cause. For example:

If a tumour in an adrenal gland is the cause, an operation to remove it will cure the condition.
For adrenal hyperplasia (see above), both adrenal glands may need to be removed. You will then need to take lifelong replacement therapy of certain adrenal hormones.
Other tumours in the body which make ectopic ACTH may be able to be removed, depending on the type of tumour, where it is, etc.
Medication to block the production or effects of cortisol may be an option.

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