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What is Cushing's and how do we get it?

Cushing's is a rare disorder which occurs whenever there is too much glucocorticoid steroid hormone in the body. The most common reason for Cushing's overall is glucocorticoid treatment for example, dexmethasone for asthma or arthritis colitis.

Spontaneous Cushing's, originating from within the body, is rare but occurs when two small glands above your kidneys (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. Approximately five to six per million new cases are identified annually. It's more common in women than in men and most commonly diagnosed between ages 20 to 40.

It is named after Harvey Cushing, an American neurosurgeon who is credited with describing this disease.

The most common cause of spontaneous Cushing's is that the Pituitary gland (a small gland at the base of the brain, behind the nose) is sending too much of a hormone called ACTH (Adrenocorticotrophic Hormone) to the adrenal glands. This causes the adrenal glands to produce too much cortisol. In this case there is an excellent 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. 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 leaflet.

Sometimes, in Cushing's, the amount of cortisol causing the condition can vary greatly. This is called, 'Cyclical Cushing's' with symptoms varying 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 does it feel like to have Cushing's?

Symptoms of Cushing's can include excessive weight gain around your trunk (your arms and legs may remain unchanged) and 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"). Some people may also notice a tendency to bruise easily and have deep red/purple stretch marks appearing on the abdomen, similar to those which occur during pregnancy but more pronounced. Some women experience irregular periods or stop having them altogether. You may also experience excessive hair growth on parts of the body including face, neck and chest. Men can experience decreased fertility and both men and women can feel a reduction or absence of sex drive. You may be feeling generally unwell, liable to depression and mood swings. In some cases, psychological problems can be severe, even being diagnosed as a nervous breakdown. 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 it diagnosed? What tests are carried out and how do they feel?

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 cause. 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.

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. 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 the doctor who will 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. (See our leaflet Pituitary Surgery.)

Most people are up and about and eating normally the following day and are back home within a few days. Recovery times vary. Depending on your particular job and circumstances, you should plan for four to six weeks, maybe longer, away from work. 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 regrow. 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 use of a drug called Desmopressin (see our leaflet on 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 (see our leaflet on Hypopituitarism and Replacement Therapy).

After successful surgery you will begin to feel better, your strength and mood will improve over time and the other symptoms will gradually diminish. This may take several weeks or 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.

Many patients will be completely cured - their cortisol levels are no longer high - after pituitary surgery - but your doctor may prefer to be cautious and call this 'remission' until some years have passed. However, if the treatment of your pituitary gland is not fully effective, then there are other solutions. You may need to have both adrenal glands removed . This is called an Adrenalectomy. In previous years this was a larger operation performed through the stomach or side with a longer hospital stay.With modern 'keyhole' techniques, however, recovery from the operation is quick and inpatient stay only a few days. After an adrenalectomy you will need hydrocortisone tablets and an additional salt-retaining hormone tablet (called fludrocortisone), both of which you will need to take for the long term and very probably for life. To prevent any recurring problems in the future, or if pituitary surgery is only partially successful, you may also be given pituitary Radiotherapy. Please see our leaflet entitled Pituitary Radiotherapy for further details of radiotherapy. Your endocrinologist may recommend adrenal surgery rather than pituitary surgery as first-line treatment.

After unsuccessful pituitary surgery - where not all of the tumour can be removed initially and the cortisol levels remain high, the choice between adrenalectomy, pituitary radiotherapy and ongoing drug treatment for Cushing's is a very complicated one - make sure you discuss this fully with your endocrinologist and understand the reasons why a particular treatment has been recommended.

In non-pituitary cases of Cushing's syndrome (see 'What is Cushing's?' above), treatment depends on the cause.

• In ectopic ACTH the underlying tumour may be removed during an operation or treated with radiotherapy or even chemotherapy.
• With adrenal tumours causing Cushing's, the offending adrenal gland(s) is usually removed.
• If the cause cannot be clearly identified then an adrenalectomy may be recommended.

Will I be cured or will I need further treatment?

The treatment described above is successful in the majority of cases. The cure is usually permanent, with no further treatment being needed, but in a minority of cases Cushing's syndrome may recur. For this reason your specialist will continue to monitor you on a regular basis to ensure symptoms do not return. Even if you are not cured, most patients find the symptoms improve. You may have to take hydrocortisone permanently, but your specialist may decide it is worth withdrawing the drug every now and then in the first two or three years after the operation. It is most important that you do not do this yourself as specialist guidance and advice are essential. In addition to hydrocortisone you may need to take several additional hormone replacement medications, such as Thyroxine, HRT and Growth hormone, to replace any lost pituitary function. Your endocrinologist will arrange this.

Aftercare

Patients who have had Cushing's always require long-term monitoring and this will be shared between your endocrinologist and GP. Because pituitary conditions are relatively rare, you might find that you will be the only patient with Cushing's that your GP is treating and (s)he might find it helpful to have a copy of our Pituitary Disease Factfile for General Practitioners.

Loss of Libido, Infertility and Relationships

You may suffer from a low sex drive, impotence or lack of self-esteem due to the imbalance of hormones and, in some cases, physical changes. This, in turn, may cause a strain on your relationship. There is also a possibility that you may have problems conceiving. It may help to talk to your partner about how you are both feeling and to consult your GP/endocrinologist.

Psychological Aspects

Cortisol is linked to mood so, not surprisingly, more than half of Cushing's patients have a major depressive disorder (MDD). Usually this depression is atypical in presentation: gaining weight and being restless or agitated are common symptoms. Memory and sleep patterns can also be affected. The degree of depression is linked to the level of cortisol.

Cushing's-induced depression is usually relieved by treatment of the Cushing's but is likely to take a little while to recede. There is no convincing evidence of a link between stress causing Cushing's or other endocrine disease.

You may wish to request a copy of our leaflet Psychological Issues in Pituitary Disease.

Other Factors to Consider

Returning to Work

The nurses will sort out a certificate to cover your stay in hospital and you will be advised how long you will be expected to remain off work. This usually depends on what your job is and whether you are self-employed or not.

Prescriptions

If you will have to take hydrocortisone, thyroxine or desmopressin permanently you will get free prescriptions for all medicines. Ask at your GP's surgery, hospital or pharmacist for form FP92 (EC92A in Scotland).

The form (which will need to be signed by your doctor) tells you what to do. You will then receive an exemption certificate. These certificates only last for a finite period after which they must be renewed. Your health authority may automatically send out an application for renewal.

Information about free prescriptions and the full list of medical conditions which qualify for exemption from prescription charges can be found in leaflet HC11, available from pharmacies and main Post Offices or on www.dh.gov.uk. If you are not sure whether you are entitled to free prescriptions, you must pay for your prescription and ask for a NHS receipt (form FP57 in England, EC57 in Scotland) when you pay; you can't get one at a later date. This form tells you how to get your money back. You must claim within three months.

If you don't qualify for free prescriptions and need more than five prescription items in four months, or more than 14 in a year, ask your pharmacist about pre-payment certificates.  This will be more a economical way of paying for a large number of prescription items.

Driving

You have a legal obligation to advise the Driver and Vehicle Licensing Agency (DVLA) if there is any reason why you should not drive. Many patients with pituitary conditions will find there are no restrictions on their driving, but you should check with your GP. The only condition likely to affect you is problems with your eyesight. Transsphenoidal surgery does not in itself limit your entitlement to drive. Your doctor or specialist will give you full advice. They may also seek extra advice from the DVLA by contacting the Medical Adviser, The Drivers' Medical Branch, 2 Sandringham Park, Swansea Vale, Llansamlet, Swansea SA6 8QD. 0870 0600 0301. There is a 24 hours answering machine.

However, it is not a good idea to rush back to driving after any major operation, regardless of whether it is legal or not.  Try to leave driving for a week after returning home and only drive for short journeys to start.

Alcohol and Replacement Hormones

There is no interaction between alcohol and these drugs, and you are allowed to drink in moderation. You should restrict yourself to one to two units of alcohol a day.

Insurance and Pensions

Each case will need to be assessed individually. As a guide, if a pituitary tumour has been completely removed, you will probably be accepted at normal rates. Of course, each insurance company will have its own practices. You need to persevere and be specific about your condition, as the people you speak to initially may not have any medical knowledge themselves. It is not unheard of, for instance, for diabetes insipidus to be confused with diabetes mellitus (sugar diabetes). If you would like more information, please email us on helpline@pituitary.org.uk or telephone 0845 450 0375.

Employment Problems

If your pituitary condition is causing you difficulties in retaining, seeking, or returning to employment, contact the HelpLine or your local Citizens Advice Bureau for the most up to date information about employment rights and where to get advice about benefits.

Personal Medical Identification

If you are taking hormone replacement medication, it is a good idea to wear a medical information bracelet or equivalent as the information will help the doctors if you have an accident and are unconscious.

Members have tried:

• MedicAlert The MedicAlert Foundation, 1 Bridgewharf, 156 Caledonian Road, London N1 9UU. Tel: 0800 581420. Website: www.medicalert.org.uk

• MediTag, 37 Northampton Street, Hockley, Birmingham B18 6DU. Tel: 0121 200 1616. Website: www.medi-tag.co.uk.

• Doctag, 31-33 West Pilton Drive, Edinburgh, EH4 4HS. Email: info@doctag.net. Website: www.doctag.net.

Other Support Organisations

Common questions

Q Why do I need so many tests?

A Diagnosis and treatment of Cushing's is very complicated. If doctors don't gather all the right information about your case then this can lead to the wrong diagnosis or the wrong treatment.

Q Are the effects on bone reversible?

A If you had Cushing's for some time before treatment commenced, you may have some loss of bone content. Bone scans can be given to check for osteoporosis. Treatment can improve osteoporosis and limit the consequences but usually cannot restore bone completely to normal.

Q Are the effects on muscle reversible?

A Muscle strength should eventually return to normal. This will happen gradually, over a period of months or even several years.

Q Will I be able to wear my dentures after the pituitary operation?

A You may find that your dentures do not fit very well until the swelling goes down. This should only take a few days.

Q I am taking hydrocortisone. What happens if I go on holiday and get an upset stomach?

A If you have serious vomiting and are unable to keep your tablets down, contact a doctor urgently as you could become ill due to lack of cortisol. The doctor may give you cortisol injections until you recover. Your endocrinologist and endocrine specialist nurse may have provided you with one of these injections and have shown you how to use it before you go away. General information is given in the Foundation's Pituitary Patient Fact File.

Q If I have an operation for any other illnesses, what happens about my hydrocortisone tablets?

A You should advise the doctors that you are on hydrocortisone and reiterate this point several times to ensure they understand. They will adjust the dose accordingly.

Q If I suffer from an infection such as bronchitis, influenza or a kidney infection, will this affect my hydrocortisone?

A The dose of hydrocortisone will need to be increased for a time while you have the infection. Your specialist should give you clear guidelines as to when you should temporarily increase your steroid dose. If in doubt, consult your GP or specialist. Do not experiment with the dosage yourself. General information is given in the Foundation's Pituitary Patient Fact File. It is advisable as a precautionary measure to request annual flu and pneumonia injections from your GP.

Q Will I always have high blood pressure or diabetes?

A Cushing's is a major cause of these problems and both are improved after successful treatment. In many cases these conditions disappear and do not need treatment, in others better control will usually be achieved on much less medication than before.

Q When will my excess facial hair improve?

A Cure of Cushing's usually results in a rapid improvement of excess facial hair in women. In many cases this will resolve completely within weeks or months. However, excess facial hair is also a very common problem in women without Cushing's, and if you have had a tendency toward this in the past then cure of the Cushing's may not completely resolve the problem. In this case there are a variety of treatments available which you should discuss with your endocrinologist.

Q Will my periods return and will I be able to have children?

A Your periods should return soon after surgery and you should be able to have children. If your fertility has been affected by the treatment, you can be given hormones to restore your fertility and enable you to have children.

Q I have heard that hydrocortisone is a steroid. Will it be bad for me?

A You will only be given the amount that your body would normally make, so you should not have any of the problems associated with steroids. In fact, people usually only need hydrocortisone in Cushing's because the cause of excessive levels of steroids has been removed.

Q Will I regain my figure?

A You should get back to your old self in time, but if you have had Cushing's for a long time before the diagnosis was made, this may take a couple of years and will require a healthy eating plan, careful dieting and exercise (gentle at first if you are not used to it).

Q Is the pituitary tumour hereditary?

A Only in very exceptional cases, less than 1%.