Addison’s disease

Addison's disease (also called primary adrenal insufficiency or hypoadrenalism) is a rare disorder of the adrenal glands.

The adrenal glands are 2 small glands that sit on top of the kidneys. They make essential hormones: cortisol, aldosterone and adrenaline. In Addison's disease, the adrenal gland is damaged, so not enough cortisol and aldosterone are produced.

About 8,400 people in the UK have the condition. It can affect people of any age, but it's most common between the ages of 30 and 50. It's also more common in women than in men.

The early symptoms look a lot like those of more common problems, such as depression or flu. You may have:

• fatigue (lack of energy or motivation)
• muscle weakness
• low mood
• loss of appetite and unintentional weight loss
• increased thirst

Over time these problems may get worse, and you may notice other symptoms such as dizziness, fainting, cramps and exhaustion. Small areas of darkened skin, or darkened lips or gums, can also appear.

These symptoms aren't always caused by Addison's disease. Even so, you should see your doctor so they can be investigated.

Addison's disease is usually the result of a problem with the immune system. The body's defences attack the outer layer of the adrenal gland (the adrenal cortex), and this disrupts the production of the steroid hormones aldosterone and cortisol. It's not clear why this happens, but it's responsible for 70% to 90% of cases in the UK.

Other possible causes include conditions that can damage the adrenal glands, such as tuberculosis (TB), although this is uncommon in the UK.

Addison's disease is treated with medicine that replaces the hormones your body is missing. You'll need to take this medicine for the rest of your life.

With treatment, the symptoms of Addison's disease can largely be controlled. Most people with the condition live a normal lifespan and stay active, with few limitations.

Many people do find, though, that they have to learn to manage bouts of fatigue. There may also be other health conditions linked to it, such as diabetes or an underactive thyroid.

If you have Addison's disease, you need to know about the risk of a sudden worsening of symptoms, called an adrenal crisis. It can happen when the level of cortisol in your body falls significantly, either because you haven't taken your medicines or because you have another illness.

An adrenal crisis is a medical emergency. Warning signs include severe nausea, confusion, fever, headache and weakness. If it's left untreated, it can be fatal. If you or someone you know has Addison's disease and is having severe symptoms, phone 999 for an ambulance.

Addison's disease is hard to spot at first, because the early symptoms look like those of many other health conditions.

The first symptoms of Addison's disease can include:

• fatigue (lack of energy or motivation)
• lethargy (abnormal drowsiness or tiredness)
• muscle weakness
• low mood (mild depression) or irritability
• loss of appetite and unintentional weight loss
• the need to urinate frequently
• increased thirst
• craving for salty foods

Dehydration can also be an early sign. It happens because your body lacks the hormone aldosterone, which is used to regulate the balance of salt and water.

Other symptoms of Addison's disease usually come on slowly, over months or even years. But extra stress on the body, such as another illness or an accident, can make your symptoms suddenly get worse.

You may go on to develop:

• low blood pressure when you stand up, which can cause dizziness and fainting
• feeling sick (nausea)
• vomiting
• diarrhoea
• abdominal, joint or back pain
• muscle cramps
• chronic exhaustion, which may cause depression
• brownish discolouration of the skin, lips and gums (hyperpigmentation), particularly in the creases on your palms, on scars or on pressure points, such as your knuckles or knees
• a reduced libido (lack of interest in sex), particularly in women

Some women may also have irregular periods or miss some periods completely. Children with Addison's disease may reach puberty later than usual.

Some people with Addison's disease also develop low blood sugar (hypoglycaemia). This can cause difficulty concentrating, confusion, anxiety and even unconsciousness (particularly in children).

If you're having symptoms of Addison's disease, see your doctor so they can diagnose or rule out the condition. These symptoms will usually improve with appropriate treatment.

If Addison's disease isn't treated, the hormone levels made by the adrenal gland slowly fall. Your symptoms then get steadily worse, and in the end they can lead to a life-threatening situation called an adrenal crisis, or Addisonian crisis.

In an adrenal crisis, the symptoms of Addison's disease come on fast and hit hard. This can happen when you already have early symptoms, or when you've had no symptoms at all.

The signs of an adrenal crisis include:

• severe dehydration
• pale, cold, clammy skin
• sweating
• rapid, shallow breathing
• dizziness
• severe vomiting and diarrhoea
• severe muscle weakness
• headache
• severe drowsiness or loss of consciousness

An adrenal crisis is a medical emergency, and it can be fatal if it isn't treated. If you think you, or someone you know who has Addison's disease, is having an adrenal crisis, phone 999 for an ambulance.

Without treatment, an adrenal crisis can lead to a coma and death. If treatment is delayed, there's also a risk that the brain won't get enough oxygen, and that can cause permanent disability.

Addison's disease happens when the outer layer of your adrenal glands, called the adrenal cortex, is damaged. Once that layer is damaged, it makes lower levels of the hormones it normally produces.

In the UK, a problem with the immune system is the most common cause of Addison's disease, accounting for 70% to 90% of cases.

Your immune system is your body's defence against infection and disease. When you're ill, it produces antibodies, a special type of protein that destroys disease-carrying organisms and toxins. These antibodies attack the cause of the illness.

But if something goes wrong with your immune system, it can start to attack your own healthy tissues and organs. This is known as an autoimmune disorder.

Addison's disease can develop if your immune system attacks your adrenal glands and severely damages your adrenal cortex. When 90% of the adrenal cortex is destroyed, your adrenal glands won't be able to produce enough of the steroid hormones cortisol and aldosterone. Once levels of these start decreasing, you'll experience the symptoms of Addison's disease.

It's not clear why some people develop this problem with their immune system, although it can run in families.

Research has shown that people with certain genes are more likely to develop autoimmune disorders. Doctors don't fully understand how these genes lead to Addison's disease and similar conditions. But it does mean your risk of developing Addison's disease is higher if you or a close family member have another autoimmune condition, such as:

• vitiligo, a chronic (long-term) condition that causes pale, white patches to develop on the skin
• type 1 diabetes, a chronic condition caused by too much glucose in the blood
• underactive thyroid gland (hypothyroidism)

Tuberculosis (TB) is the most common cause of Addison's disease worldwide, though it's rare in the UK. TB is a bacterial infection that mostly affects the lungs, but it can spread to other parts of your body. If it damages your adrenal glands, it can cause the condition.

Other possible causes of Addison's disease include:

• infections, such as those linked to AIDS, or fungal infections
• a haemorrhage, which means very heavy bleeding into the adrenal glands, sometimes associated with meningitis or other types of severe sepsis
• cancer, if cancer cells from elsewhere in your body spread to your adrenal glands
• amyloidosis, a disease where amyloid, a protein produced by your bone marrow cells, builds up in your adrenal glands and damages them
• surgical removal of both adrenal glands (adrenalectomy), for example to remove a tumour
• adrenoleukodystrophy (ALD), a rare, life-limiting, inherited condition affecting the adrenal glands and nerve cells in the brain that most often affects young boys
• certain treatments needed for Cushing's syndrome, a collection of symptoms caused by very high levels of cortisol in the body

To help diagnose Addison's disease, your doctor will first ask about your symptoms and go through your medical history. They're also likely to ask whether anyone in your family has an autoimmune disorder (a condition caused by a problem with their immune system).

Your doctor will then look at your skin for any brownish discolouration (hyperpigmentation), particularly in certain areas, such as:

• where skin creases on your palm
• in your elbow crease
• on any scars
• your lips and gums

However, hyperpigmentation doesn't occur in all cases of Addison's disease.

You'll also be tested for low blood pressure (hypotension) while you're lying down and again shortly after you stand up. This is to see whether you have postural or orthostatic hypotension (low blood pressure when you change position).

If your doctor suspects Addison's disease, you'll have blood tests to measure the levels of sodium, potassium and cortisol in your body. A low sodium level, a high potassium level or a low cortisol level may point to Addison's disease.

You may also need to see a hospital hormone specialist (an endocrinologist), who can test your blood for the following:

• a low level of the hormone aldosterone
• a high level of adrenocorticotrophic hormone (ACTH)
• a low level of glucose (sugar used for energy)
• positive adrenal antibodies (antibodies designed to attack the adrenal gland)

Any one of these could be a sign of Addison's disease.

If your blood cortisol is low, or your symptoms strongly point to Addison's disease, you'll need a synacthen stimulation test to confirm the diagnosis.

Your doctor may send you to an endocrinology unit for the test (this is a unit that specialises in the study of hormones). How quickly you're referred depends on how severe your symptoms are.

Synacthen is a man-made (synthetic) copy of the adrenocorticotrophic hormone, or ACTH. Your body makes ACTH naturally in the pituitary gland, a pea-sized gland below the brain, and it tells the adrenal glands to release the hormones cortisol and aldosterone.

When synacthen is given, the adrenal glands should react just as they would to ACTH, and release cortisol and other steroid hormones into the blood.

First, a blood sample is taken and tested for cortisol. Then you're given an injection of synacthen into your arm. After 30 and 60 minutes, another blood sample is taken to measure cortisol again.

If the ACTH level is high but the cortisol and aldosterone levels are low, this usually confirms Addison's disease.

Besides the synacthen stimulation test, your doctor may also check whether your thyroid gland is working properly. The thyroid sits in your neck and makes hormones that control your body's growth and metabolism.

People with Addison's disease often have an underactive thyroid gland (hypothyroidism), which means the gland doesn't produce enough hormones. Your endocrinologist (a specialist in hormone conditions) can find out whether you have hypothyroidism by testing the levels of certain hormones in your blood.

Sometimes the specialist treating your Addison's disease will send you for a scan of your adrenal glands. This may be a computerised tomography (CT) scan or a magnetic resonance imaging (MRI) scan.

If Addison's disease is left untreated, it eventually leads to an adrenal crisis. That's when the symptoms of Addison's disease come on quickly and severely.

In an adrenal crisis there isn't enough time to do a synacthen stimulation test to confirm the diagnosis.

If possible, the doctors will take blood and test it for any of the abnormalities listed above. While you wait for the results, they may start treatment with steroid injections and fluids containing salt and glucose.

Read more about treating Addison's disease

If you have Addison's disease, you'll need to take medicine every day to replace the hormones your body has lost. This should help you live an active life, though many people find they still have to manage their tiredness.

Sometimes the underlying cause of Addison's disease can be treated. Tuberculosis (TB) is one example, and it's treated with a course of antibiotics lasting at least 6 months.

Most cases, however, are caused by a problem with the immune system, and that can't be cured.

Treatment for Addison's disease usually means corticosteroid (steroid) replacement therapy for life. The medicine replaces the hormones cortisol and aldosterone, which your body no longer produces. You'll usually take it as tablets, 2 or 3 times a day.

In most cases, a medicine called hydrocortisone replaces the cortisol. Prednisolone or dexamethasone can also be used, though they're less common.

Aldosterone is replaced with a medicine called fludrocortisone. Your doctor may also ask you to add extra salt to your daily diet, although if you're taking enough fludrocortisone this may not be necessary. Most people are told to watch their salt, but you're different. If you feel the urge to eat something salty, you should eat it.

In general, the medicines used for Addison's disease don't have side effects, unless your dose is too high. If you take a higher dose than necessary for a long time, there's a risk of problems such as weakened bones (osteoporosis), mood swings and difficulty sleeping (insomnia).

Many people with Addison's disease find that their medicine lets them carry on with their normal diet and exercise routines. Bouts of fatigue are common too, though, and it can take some time to learn how to manage these periods of low energy.

Some people find that taking regular doses of medicine is restrictive and affects their daily life or emotional health. Missing a dose, or taking it late, can also lead to exhaustion or insomnia.

Some people develop other health conditions alongside it, such as diabetes or an underactive thyroid, and these need extra treatment and management.

You'll usually need to see an endocrinologist every 6 to 12 months, so they can review your progress and adjust your medicine dose if necessary. In between these visits, your doctor can support you and give you repeat prescriptions.

If you fail to take your medicine, you could develop a serious condition called an adrenal crisis. So you must:

• remember to collect your repeat prescriptions
• keep spare medicine as necessary (for example, in the car or at work), and always carry some spare medicine with you
• take your medicine every day at the right time
• pack extra medicine if you are going away (usually double what you would normally need), plus your injection kit (see below)
• carry your medicine in your hand luggage if you are travelling by plane, with a note from your doctor explaining why it is necessary

You could also tell close friends or colleagues that you have Addison's disease. Explain the signs of adrenal crisis to them, and what they should do if you have one.

It's also a good idea to wear a medical alert bracelet or necklace that tells people you have Addison's disease.

After a serious accident, such as a car crash, a healthy person makes more cortisol. This helps you cope with the stress and the extra strain on your body that comes from serious injury. Your body can't produce cortisol, so you'll need a hydrocortisone injection to replace it and prevent an adrenal crisis.

A medical alert bracelet tells any medical staff treating you about your condition and what medicine you need.

Medical alert bracelets and necklaces are pieces of jewellery engraved with your medical condition and an emergency contact number. They are available from a number of retailers. Ask your doctor if there's one they recommend, or go to the MedicAlert website.

If you need to stay in hospital, the healthcare professionals responsible for your care will also need to know that you need steroid replacement medicine throughout your stay. This advice still applies if you're not supposed to eat or drink (nil by mouth) for any reason.

At certain times, your medicine may need to be adjusted because your body is under extra strain. You may need a higher dose if any of these happen:

• an illness or infection, particularly if you have a high temperature of 37.5C (99.5F)
• an accident, such as a car crash
• an operation, or a dental or medical procedure (such as a tooth filling or endoscopy)
• strenuous exercise that isn't usually part of your daily life

A higher dose helps your body cope with the added stress. Your endocrinologist will monitor your dose and advise you about any changes. As time goes on, you get used to living with Addison's disease and learn what can set off your symptoms, and you may then be able to adjust your medicine yourself. But if you're unsure, always check with your doctor or specialist.

If you have Addison's disease, you and a partner or family member may be trained to give an injection of hydrocortisone in an emergency.

You might need it if you go into shock after an injury, or if you're vomiting or have diarrhoea and can't keep down the medicine you take by mouth. This can also happen if you're pregnant and have morning sickness. Your endocrinologist will talk with you about when an injection might be necessary.

If you do give emergency hydrocortisone, always phone your doctor straight afterwards. Check what out-of-hours services are available in your area, in case the emergency happens outside normal working hours.

You can also register yourself with your local ambulance service. That way they have a record that you need a steroid injection or tablets, if you need their help.

Adrenal crisis, also called Addisonian crisis, needs urgent medical attention. If you or someone you know is having an adrenal crisis, phone 999 for an ambulance.

The signs of an adrenal crisis are:

• severe dehydration
• pale, cold, clammy skin
• sweating
• rapid, shallow breathing
• dizziness
• severe vomiting and diarrhoea
• severe muscle weakness
• headache
• severe drowsiness or loss of consciousness

In hospital, you'll be given a large amount of fluid through a vein in your arm to rehydrate you. The fluid contains a mixture of salts and sugars (sodium, glucose and dextrose), which replace what your body is lacking. You'll also have an injection of hydrocortisone to replace the missing cortisol hormone.

The doctors will also treat whatever brought on the crisis, such as an infection.