Cushing's Disease

What is Cushing’s and why do we get it?
What does it feel like to have Cushing’s?
Diagnosis of Cushing’s
How is Cushing's treated?


What is Cushing’s and why do we get it?

Cushing’s syndrome develops if your body makes too much cortisol hormone.

Symptoms usually develop gradually and so the diagnosis may not be clear for some time. The condition is named after Harvey Cushing, an eminent American neurosurgeon, who described the first patients with this condition in 1912.

Cortisol is a hormone made by the adrenal glands (two small glands which lie just above each kidney) and it is vital for life. It has several functions including:
• Helps to regulate blood pressure
• Helps to regulate the immune system
• Helps to balance the effect of insulin to keep blood sugar normal
• Helps the body to respond to stress

The most common reason for Cushing's overall is glucocorticoid treatment - for example taking a steroid such as prednisolone for asthma, arthritis or colitis.

Spontaneous Cushing's, originating from within the body is rare, but occurs when the adrenal glands are making too much of a hormone called cortisol (the body’s natural glucocorticoid steroid hormone). This may happen for one of several reasons, so you will have tests to find out which reason applies to you. The quoted incidence of Cushing’s is 1 in 200,000 but it is now being found more frequently when it is specifically investigated. The difficulty is that the symptoms of Cushing’s can be very wide ranging and thus the diagnosis may not necessarily be considered; it can be difficult to establish at the earlier stages and this can cause a delay in diagnosis.

Far more women than men suffer from Cushing’s, but it isn’t known why.  It is most commonly diagnosed between the ages of 30 to 40. Although it is rare in children, some as young as six have been diagnosed. There are no environmental triggers known and it’s not hereditary.

The commonest cause of spontaneous Cushing’s (around 70%) is a small benign tumour (growth) of the pituitary gland. This produces the hormone called ACTH, (adrenocorticotrophic hormone), which goes through the blood stream to the adrenal glands and causes them to release too much cortisol. In this case there is a good chance that an operation on your pituitary gland will solve the problem. Alternatively, there could be a small growth in another part of your body which is having the same effect (this is called ectopic ACTH). If so, removing this growth will usually solve the problem. Lastly, there may be a small growth in one of the adrenal glands themselves, in which case an operation will be needed to remove that gland. In some circumstances it may be necessary to remove both adrenal glands to solve the problem.

Strictly speaking, if the source of the problem is the pituitary gland, then the correct name is Cushing's disease. Whereas, if it originates anywhere else, then the correct name is Cushing's syndrome. The term ‘Cushing’s’ is used throughout this booklet.

Sometimes, the amount of cortisol causing the condition can vary greatly. This is called ‘Cyclical Cushing’s’ with varying symptoms, often over months or even years depending on the levels of cortisol. This can cause difficulty and delays in diagnosis. Occasionally, repeated testing by your endocrinologist will be needed to assess whether you have this more uncommon type of Cushing’s.


What are the symptoms of Cushing's?

Symptoms of having Cushing’s are very varied, and usually several are present which can include:
• Excessive and sudden (or at times more gradual) onset of weight gain around your trunk; your arms and legs may remain unchanged and can become quite thin compared to your body)
• Weak muscles, especially in your legs
• Your face tends to be rounder and redder than normal (a classic symptom of Cushing’s known as ‘moon face’) and you may have developed acne
• Your bones may have become weaker (an X-ray may show a fractured rib for instance), due to steroid-induced osteoporosis (thinning and brittleness of bones) and therefore you have an increased risk of fracture
• Your blood pressure may be higher than normal (hypertension) and you could have developed diabetes mellitus (‘sugar diabetes’) and excess thirst
• Some people may also notice a tendency to bruise easily and have deep red/purple stretch marks (striae) appearing on the abdomen, similar to those which occur during pregnancy but are more pronounced
• Some women experience irregular periods or stop having them altogether
• You may also experience excessive hair growth on parts of the body and usually the face in women. Men can experience decreased fertility and both men and women can feel a reduction, or absence of sex drive (libido)
• You may be feeling generally unwell, and more susceptible to infections
• Mood swings - such as being more irritable, feeling depressed or anxious. In some cases, psychological problems can be severe, even being diagnosed as a nervous breakdown
• In children it may show itself by growth stopping and weight increasing

Cushing's affects many parts of the body, both mentally and physically, and affects different people in different ways.

Because Cushing's progresses slowly and gradually, in most cases, it can go unrecognised for quite some time, sometimes resulting in depression. Looking back, many patients realise that there were clues to the condition two or more years before they were referred to an endocrinologist. However lack of Cushing’s knowledge, at the time meant they were unaware of the condition.


How is Cushing's diagnosed?

The tests used to diagnose Cushing’s are complicated and may take some time; they may also need to be repeated on several occasions. You may have them as an inpatient or an outpatient.

The first tests are to establish that Cushing’s is present. If Cushing’s is likely then further tests establish the location. This is because most people who gain weight and who have high blood pressure or diabetes or problems with excess hair do not actually have Cushing’s. To see if you have Cushing’s you will probably be given a tablet called dexamethasone. In people who do not have Cushing's, taking this tablet will completely suppress the production of the hormone cortisol. You may also have a series of blood tests and urine tests and even saliva tests. The urine test involves collecting all the urine you pass during 24 hours (for example, between nine o'clock one morning and nine o'clock the next morning). The hospital will provide a special container for this and you will be told how to take accurate and clean samples.

If these initial tests indicate that Cushing's is likely, you will then need further tests to find its location. You may be admitted to hospital for these, and it is likely that you may be referred to a hospital where they are very familiar with Cushing’s. Tests include blood samples taken throughout the day; a higher dose of dexamethasone; an injection of corticotrophin releasing hormone (CRH) which stimulates the pituitary and lastly, measuring the blood coming from the pituitary gland.

Your doctor may decide to treat you in the meantime with drugs, such as metyrapone or ketoconazole, to reduce the amount of cortisol produced by your adrenal glands. If so, you may have to spend two or three days in hospital to assess your response to the tablets or attend regularly as an outpatient. At the end of all these blood tests your arms might be quite bruised, a tendency to bruise easily is typical of Cushing’s. This tendency will diminish after the Cushing’s is successfully treated by reducing cortisol levels. ‘Success’ is achieved in around 70% of patients.

You will also have your pituitary and/ or adrenal glands scanned, using a type of magnetic scan called an MRI scan, or by a form of X-Ray called a CT scan. You may be given an injection during the scan to improve the results. A minority of patients are allergic to this injection, so do tell the specialist if you have asthma or any allergies. The scan does not hurt but the MRI machine can be very noisy and it may involve being inside the scanner for around half an hour. If you think this will make you claustrophobic or nervous, tell your GP who may give you something to help you relax. If ectopic ACTH is a possibility you may be scanned from head to toe to look for the cause.

Another test which may be carried out initially, or possibly during the follow-up to treatment, is a bone mineral density test. This will establish whether you have lost bone density and might be at risk of developing osteoporosis (thinning and brittleness of the bones).


How is Cushing's treated?

If your Cushing's is caused by a pituitary tumour (Cushing's disease), you will usually need an operation. It is carried out under a general anaesthetic and involves making a small cut - either in front of the upper teeth behind the upper lip or inside the nose. This is called transsphenoidal surgery. By going behind the nose in this way, the surgeon can see your pituitary gland without having to operate on the main part of your head. Sometimes the back of the nose needs patching with tissue taken from under the skin of the thigh or abdomen during the operation which will leave a small scar there. Please see our Surgery & Radiotherapy booklet.

Most people are up and about and eating normally the following day and are back at home within a few days. Recovery times can vary. Depending on your particular job and circumstances, you should plan to be away from work for four to six weeks, maybe longer. You will need to avoid blowing your nose for three weeks or more while it heals and your front teeth may feel a bit numb for a while, occasionally permanently. You may also lose your sense of smell for weeks or months - although this usually returns to normal as the nerves re-grow. For a few days after the operation some patients feel very thirsty and need to pass urine more than normal. This condition, Diabetes Insipidus (DI), is usually temporary but occasionally can become permanent. It can be treated by using a drug called desmopressin. Please see our leaflet called Diabetes Insipidus. You may also notice peeling of the skin as the cortisol levels fall (this is a good sign). Occasionally it is necessary to carry out a second operation if the first is not completely successful. This can sometimes be done within seven to ten days.

You will need further hormone tests, either immediately and/or four to six weeks after the operation. Again, this may involve a few days in hospital. These tests are designed to show whether or not the operation has been a success, and whether you have developed deficiencies of other pituitary hormones, known as hypopituitarism, which may need replacement tablets. Please see our booklet called The Pituitary Gland.

Paradoxically, after successful surgery you may feel worse for several weeks and occasionally months before you begin to feel better. Eventually, however, your strength and mood will improve over time and the other symptoms will gradually diminish. This usually takes several months, but be patient - it will happen. You may have to take replacement cortisol (which is called ‘hydrocortisone’ when it is in tablet form) or another steroid tablet such as prednisolone, for some time after your operation to compensate for a temporary reduction in your body's ACTH production. This occurs because the normal control mechanisms are ‘switched off’ after being exposed to too much cortisol for so long. Hydrocortisone is taken in the form of tablets, usually two or three times a day. If prescribed and you don’t take the tablets (or when they are deliberately not given immediately after the operation or during reassessment tests) you will probably feel generally weak, tired and ‘ill’. However you will feel better after you begin to take the tablets again.