Causes

Addison's disease develops when the outer layer of your adrenal glands (adrenal cortex) is damaged, reducing the levels of hormones it produces.

Problems with the immune system

A problem with the immune system is the most common cause of Addison's disease in the UK.

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

However, if you develop a problem with your immune system, it can start to attack your own healthy tissues and organs. This is called 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 will not be able to produce enough of the steroid hormones cortisol and aldosterone. Once levels of these start decreasing, you'll experience 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.

Genetics

Research has shown that some people with certain genes are more likely to develop autoimmune disorders.

It's not clear how these genes lead to Addison's disease and similar conditions, but it does mean your risk of developing Addison's disease is increased if you or a close family member have another autoimmune condition, such as:

• vitiligo – a long-term condition that causes pale, white patches to develop on the skin
• type 1 diabetes – a long-term condition caused by your body not producing insulin
• underactive thyroid (hypothyroidism)

Other causes

Tuberculosis (TB) is the most common cause of Addison's disease worldwide, but it's rare in the UK.

TB is a bacterial infection that mostly affects the lungs but can also spread to other parts of your body. It can cause Addison's disease if it damages your adrenal glands.

Other possible causes of Addison's disease include:

• infections – such as those linked to AIDS, or fungal infections
• a haemorrhage – 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 that affects the adrenal glands and nerve cells in the brain, and is mostly seen in young boys
• certain treatments needed for Cushing's syndrome – a collection of symptoms caused by very high levels of cortisol in the body

Secondary adrenal insufficiency

The production of hormones from the adrenal gland can also be affected by damage to the pituitary gland – a pea-sized gland located below the brain that produces a hormone that stimulates the adrenal gland. This is called secondary adrenal insufficiency and is a separate condition to Addison's disease.

Secondary adrenal insufficiency can occur if your pituitary gland becomes damaged – for example, because of a tumour on the pituitary gland (pituitary adenoma).