Addison's disease (chronic adrenal insufficiency) is a rare and progressive disorder that affects between one and six in every 100,000 people. It affects people of both sexes and all ages.

The human body has two adrenal glands, one on top of each kidney. These glands form part of the endocrine system, which works with the nervous system and the immune system to help the body cope with different events and stresses. Addison's disease is caused by the inability of the adrenal glands to make sufficient amounts of regulating hormones.

Adrenaline is the best known of the hormones that are secreted by the adrenal glands in the adrenal medulla (the central part of the gland). The adrenal cortex (the outer part) also produces important hormones, the corticosteroids. They include cortisol, aldosterone and supplementary sex hormones.

In a person with Addison's disease, only the adrenal cortex is affected. The person cannot produce enough glucocorticoid or cortisol and, occasionally, also fails to produce sufficient mineralocorticoid. Levels of aldosterone are nearly always low in people with Addison’s disease.

Causes of Addison's disease
Most cases of Addison's disease are caused by an autoimmune response that attacks and damages the adrenal glands over time. Other causes include:
Infection
Cancer
Surgical removal of particular tumours in the adrenal or pituitary glands or the hypothalamus.
Symptoms of Addison's disease
The symptoms of Addison's disease can include any or all of the following:
Loss of appetite and weight
Nausea, vomiting or diarrhoea
Muscle weakness
Chronic, worsening fatigue
Low blood pressure
Salt cravings
Dehydration
Hypoglycaemia, or low blood sugar levels (especially in children)
Increased pigmentation of the skin, particularly around scars and bony areas
Irregular or no menstrual periods in women
Mood swings, mental confusion or loss of consciousness.
These symptoms can develop quickly (especially in children and teenagers), or progress slowly for 20 years or more. Many symptoms can mimic other diseases, so diagnosis can be delayed.

The hormone cortisol
Cortisol is produced by the outer layer of the adrenal gland, called the adrenal cortex. The quantities of cortisol released by the adrenal glands are closely monitored by the master gland of the endocrine system, the pituitary, which is located in the brain.

The workings of the pituitary are governed by another brain structure, the hypothalamus. When cortisol levels are too low, the pituitary secretes the stimulating hormone adrenocorticotropin (ACTH). On the other hand, high levels of cortisol cause the pituitary gland to decrease ACTH secretion, which slows cortisol production.

Cortisol plays many vital roles and is essential to many body functions because it:
Works with adrenaline to help the body manage physical and emotional stress
Converts protein into glucose to boost flagging blood sugar levels
Works in tandem with the hormone insulin to maintain constant blood sugar levels
Reduces inflammation
Helps the body maintain a constant blood pressure
Helps the workings of the immune system.
The hormone aldosterone
Aldosterone is a mineralocorticoid, also produced by the adrenal cortex. The amount of aldosterone in the body is monitored by the kidneys, which secrete hormones to increase or decrease aldosterone production. Aldosterone regulates electrolytes (such as sodium and potassium) in the blood. This helps to maintain blood pressure and heart function.

If too much sodium is excreted by the kidneys, a considerable amount of body fluid is also lost. This reduces blood volume and drops blood pressure. Too much or too little potassium can affect the way the heart functions.

Primary adrenal insufficiency
Addison's disease can occur gradually, and is defined when approximately 90 per cent of the adrenal gland(s) is damaged. This is known as primary adrenal insufficiency. Around seven out of 10 cases of Addison's disease are caused by an autoimmune response, where the body's own immune cells attack and destroy the adrenal glands. In some cases, other glands of the endocrine system are affected by an autoimmune response, in a condition called polyendocrine deficiency syndrome.