Addison's disease

Addison's disease is caused by damage to the adrenal glands, which make

hormones to control the bodys response to stress, and balance body salt and
water. Treatment is with tablets and some lifestyle adaptations to ensure
patients remain well.

Portrait of Thomas Addison.

Alternative names for Addisons disease

Primary hypoadrenalism; adrenal failure; addison disease; addison syndrome; adrenal
insufficiency; hypoadrenalism.

What is Addisons disease?

The adrenal glands are triangular in shape, roughly up to three inches (7.6cm) by one
inch (2.5cm) in size, and one gland sits on the top of each kidney. The outer part of
the adrenal gland (called the cortex) makes three separate types of hormone:

Glucocorticoids (especially cortisol);

Mineralocorticoids (especially aldosterone); and

Sex steroids (or androgens).

Cortisol controls blood sugar levels and is essential to maintaining normal body
function (metabolism). It is released by the adrenal glands throughout the day but its
production increases in times of stress, eg, during illness or injury. Aldosterone is
essential to keeping a normal level of salt and water in the bloodstream. Adrenal
androgens control body hair growth in women but have little importance in men.

Addisons disease is caused by the destruction of the cortex of each adrenal gland.
This means that the adrenal gland cannot produce the hormones glucocorticoids
(especially cortisol), mineralocorticoids (especially aldosterone) and sex
steroids. People with Addisons disease develop symptoms as a result of this loss of
adrenal hormones.

What causes Addisons disease?

By far the most common cause of Addisons disease is autoimmunity. This is known as
autoimmune Addisons disease. Normally the bodys immune system attacks invading
viruses and bacteria to defend the body. In cases of autoimmunity, the immune
system makes a mistake, attacking and destroying the adrenal cortex as if it was an
infection.
Rare causes of Addisons disease include infections such as tuberculosis, removal of
the adrenal glands by surgery, bleeding into the adrenal glands (for instance after
abdominal injuries), cancer of the adrenal glands and genetic defects such as
adrenoleukodystrophy.
The pituitary gland produces hormones that affect the adrenal gland. If the pituitary
gland stops working properly, this can cause secondary adrenal insufficiency.

What are the signs and symptoms of Addisons disease?

The signs and symptoms of Addisons disease usually appear very gradually, as it takes
months or years for the adrenal cortex to be destroyed significantly enough to cause
symptoms. General signs such as tiredness, weight loss, feeling faint, depression and
aches in the joints, muscles and abdomen are all common signs of Addisons disease,
but could also be caused by a wide range of other diseases. Nausea, vomiting,
diarrhoea and a craving for salt may also be symptoms.
However, there are specific symptoms of the disease, in particular the appearance of
increased skin colour, just like a suntan. New scars may heal with too much colour
around them and this can also be noticed in skin creases on the palms of the hands
and inside the mouth. In women, loss of body hair may occur and periods may stop.
Once 90% or more of the adrenal gland cortex has been damaged, there is a very high
risk that the body will not be able to cope with stresses like infection or
injuries. When these happen, the patient can become increasingly ill very quickly.
This is called an adrenal crisis. Blood pressure becomes very low leading to fainting,
blood sugar levels drop and the patient becomes seriously ill with dehydration. If not
treated as an emergency, this can lead to death.
The adrenal glands depend on the pituitary gland to work properly. When the
pituitary gland is damaged, the adrenal glands do not function because they do not
receive stimulation from a pituitary hormone called adrenocorticotropic hormone; in
this type of adrenal failure (called secondary adrenal insufficiency), there is no
pigmentation of the skin and aldosterone secretion is not affected.

How common is Addisons disease?

One in 15,000 people have Addisons disease, so it is a rare condition. Around two to
three times more women than men get this disease, because autoimmunity is more
common in women. The peak age of the start of Addisons disease is between 30 and
50, but it can happen at any age. Those people with other autoimmune diseases,
such as Graves disease, hypothyroidism, type 1 diabetes, pernicious anaemia and
vitiligo, have a greater risk of also developing autoimmune Addisons disease.

Is Addisons disease inherited?

There is often a family history of thyroid disease or other autoimmune diseases in
people who have autoimmune Addisons disease. Very rare genetic disorders may
cause different effects such as abnormal development of the adrenal glands,
problems with production of adrenal hormone or failure of the adrenal glands to
respond to the pituitary adrenocorticotropic hormone.

How is Addisons disease diagnosed?

There may be some clues from simple blood tests, such as a low sodium level or a
high potassium level in the blood. Diagnosis depends on showing that the secretion of
cortisol is low and that the adrenal glands themselves are damaged. The most
commonly used test is called the short synacthen test, where a hormone similar to
pituitary adrenocorticotropic hormone is injected into the bloodstream to stimulate
the adrenal glands. The cortisol level in the blood is measured immediately before
the injection is given and again after 30-60 minutes. For more information on
diagnosis, see our information leaflet on adrenal insufficiency in the topical issues
section of this website.
If the adrenal glands are healthy, cortisol production in the second sample will
exceed a certain level, commonly 500-550 nmol/l. By contrast, failing adrenal glands
will not be able to produce this amount of cortisol. It is important that this test is
carried out under the supervision of an endocrinologist.
Drawing only baseline blood samples for cortisol without injecting
adrenocorticotropic hormone to stimulate cortisol production, is only of very limited
value in the diagnosis of Addisons disease as this does not reflect the ability of the
adrenal glands to respond to stress with increased production of cortisol. Stress such
as surgery or injury modifies cortisol production. This means that a certain cortisol
concentration may be appropriate in a relaxed patient, but much too low for a
severely distressed patient. Only a dynamic function test, commonly the short
synacthen test described above, can give a conclusive answer, supported by the
clinical judgement of an experienced endocrinologist.
Measuring adrenocorticotropic hormone levels in the blood can show whether the
adrenal glands themselves are damaged, as damage causes the hormone level to
rise. Antibodies which act against the adrenal glands can be measured in the blood
to show that autoimmunity is the cause of the adrenal damage. If other causes
besides autoimmunity are suspected, further tests are needed such as a scan of the
adrenal glands. Testing is usually done as an outpatient unless the case is critical
because of an adrenal crisis.

How is Addisons disease treated?

Treatment of Addisons disease is usually managed as an outpatient. It consists of

cortisol replacement using hydrocortisone tablets (usually taken two to three times a
day) and aldosterone replacement using fludrocortisone tablets (usually taken once a
day). The exact medication regime will vary depending on the individual and should
be reviewed at regular intervals.
Adrenal sex hormone replacement can sometimes be offered to women because
there is some evidence that replacing adrenal sex hormones with a drug
called dehydroepiandrosterone might improve sex drive and general
wellbeing. However, side-effects such as acne and facial hair growth can occur, and
more research is needed in this area. It is not required for men as they also produce
the sex hormones from their testes.
When a patient has an adrenal crisis, they require immediate admission to hospital as
an emergency. Treatment consists of immediate hydrocortisone injections, fluid and
sugar replacement and careful monitoring.

Are there any side-effects to the treatment?

When properly monitored and controlled, there should be no side-effects to
treatment. In Addisons disease the body cannot cope adequately with stress, so
people with Addisons disease will not naturally produce enough cortisol if they
become ill. Normally this is helped by doubling their dose of hydrocortisone for three
days after any significant illness, stress or surgery.
A Medic-Alert necklace or bracelet to alert doctors should be worn by people with
Addisons disease in case they are brought into hospital unconscious. If someone with
Addisons disease cannot take tablets because of vomiting, they need to take the
emergency hydrocortisone injection supplied and they must contact a doctor
straightaway so that hydrocortisone can be continued to be given by injection. When
travelling to places where hospital care may be difficult to find in an emergency, it is
essential to carry hydrocortisone for injection and the patient and any companions
must know how to give this injection.

What are the longer-term implications of Addisons disease?

Although Addisons disease is a lifelong condition, it can be very successfully treated
with daily medication and patients can lead full and active lives.
There are no long-term implications provided that tablets are taken, the advice given
above is followed, and treatment is regularly monitored (at least once a year). At
these visits, checks should be made on the hydrocortisone emergency kit to ensure it
is within date of expiry and that patients know how to use this. People with Addisons
disease are at increased risk of developing other autoimmune diseases (such as
thyroid disease) and these should be checked for at annual hospital appointments.