Addison's disease
Causes

Addison's disease develops when the outer layer of the 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, accounting for 70% to 90% of cases.

The immune system is the body's defence against infection and disease. The 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 a problem with the immune system develops, it can start to attack healthy tissues and organs. This is called an autoimmune disorder. Some examples of autoimmune diseases are:

• Rheumatoid arthritis.
• Systemic lupus erythematosus (lupus).
• Inflammatory bowel disease (IBD).
• Multiple sclerosis (MS).
• Type 1 diabetes mellitus.
• Psoriasis.

Addison's disease can develop if the immune system attacks the adrenal glands and severely damages the adrenal cortex.

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 the risk of developing Addison's disease is increased if the patient or a close family member has 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 the body not producing insulin
• underactive thyroid gland (hypothyroidism)

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 the body. It can cause Addison's disease if it damages the 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 metastasis – if cancer cells from elsewhere in the body spread to the adrenal glands
• amyloidosis – a disease where amyloid, a protein produced by the bone marrow cells, builds up in and damages the adrenal glands
• 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 - ACTH - 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 the pituitary gland becomes damaged – for example, because of a tumour on the pituitary gland (pituitary adenoma).

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