Addison's Disease

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 most well 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 or aldosterone.

Causes
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
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). Conversely, high levels of cortisol prompt the pituitary 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.

Polyendocrine deficiency syndrome
There are two types of this disorder and both types tend to run in families:

* Type I - is more common in children. Symptoms include underactive parathyroid, pernicious anaemia, recurring candida infections, chronic active hepatitis and slow sexual development.
* Type II - (Schmidt's syndrome) is more common in younger adults. Symptoms include underactive thyroid, diabetes mellitus and slow sexual development.

Other conditions related to primary Addison's disease are:

* Adrenomyeloneuropathy (AMN) - which can occur in some adults. It affects the spine, and is degenerative over time.
* Adrenoleukodystrophy (ALD) - which occurs (rarely) in some children (one in 100,000), especially males. It can cause brain damage and can be fatal. Survivors often develop AMN.

Treatment for primary Addison's disease is with glucocorticoid and mineralocorticoid replacement for life.

Secondary adrenal insufficiency
Sometimes, Addison's disease is caused by the pituitary gland's inability to produce sufficient amounts of ACTH, which means the adrenal glands aren't prompted to secrete cortisol. This is known as secondary adrenal insufficiency. Causes may include:

* Some medications - inflammatory disorders, such as rheumatoid arthritis and asthma, are often treated with prolonged or high dose steroids (glucocorticoid replacements). If the dose is suddenly stopped, or not reduced by appropriate tapering measures, the pituitary gland may respond by failing to produce enough ACTH. This situation can sometimes be reversed.
* Cushing's disease - a benign tumour of the pituitary gland that produces ACTH. This results in too much cortisol being produced. Treatment requires surgical removal of the tumour and, in some cases, removal of damaged adrenal gland(s).
* Other causes - infections, reduced blood flow, radiotherapy and some neurosurgery can damage the pituitary gland or hypothalamus, and decrease ability to produce ACTH.

Treatment for secondary Addison's disease is with glucocorticoid replacement only.

Addisonian crisis
A sudden, acute worsening of symptoms is known as an Addisonian crisis. It can be caused by:

* Extreme stress - an accident, excessive heat or physical exertion.
* Severe illness - especially dehydration from vomiting or diarrhoea.
* Sudden shock - for example, the death of a significant person.

The symptoms of Addisonian crisis include:

* Violent pain in the abdomen, back and legs.
* Nausea, vomiting or diarrhoea.
* Low blood pressure, low blood sugar, high potassium, low sodium and a rapid heart rate.
* Possible mental confusion and loss of consciousness.

Prompt emergency hospital treatment must be sought, including intravenous fluids, increased steroid medication and saline. Many Addisonians wear a medical alert bracelet or pendant with information and identification, and carry a hydrocortisone injectable for use in emergencies. They will still need hospitalisation and ongoing monitoring.

If untreated, an Addisonian crisis can be fatal.

Diagnostic tools
Diagnosis of Addison's disease may involve:

* Complete detailed family history, with special attention to any other endocrine disorders.
* Biochemical tests, which measure cortisol levels before and after a challenge injection of synthetic ACTH, known as a 'short synacthen test'. A 'long synacthen test' is done over several days in hospital. Synacthen tests will indicate the person's baseline level of cortisol production and their response to an increased need for cortisol in the body. An Addisonian may show a flat or reduced response.
* Blood electrolyte and plasma renin tests will indicate if there is a need for mineralocorticoid replacement.
* Anti-adrenal antibody test. If the result is positive, primary Addison's disease is definitively diagnosed. However, even if these antibodies do not exist, the person may still have Addison's disease.
* X-rays, ultrasounds and CAT scans of the abdominal region to check for visual signs of damage and the size of adrenal glands.

Treatment options
Treatment aims to bolster or replace insufficient or absent steroid components. Glucocorticoid replacement is essential for primary and secondary Addisonian patients, and must be taken for life. Treatment should:

* Be tailored to each person over the course of their life.
* Be altered, in consultation with a doctor, during illness or other stressful events.
* Allow for the different needs of children and young adults.

Where to get help

* Your doctor
* Endocrinologist
* Australian Addison's Disease Association Tel. (02) 6652 4761

* Australian Pituitary Foundation Tel. 1300 331 807 email: support@pituitary.asn.au

Things to remember

* Addison's disease is a progressive disorder, characterised by the inability of the adrenal glands to produce sufficient hormones.
* Causes can include infection, damage, and an autoimmune response that prompts the immune system to attack and destroy the adrenal glands.
* Treatment includes steroid replacement therapy that must be managed for life.
* An Addisonian crisis can be fatal unless treated quickly and appropriately.
ALINTIDIR.
ORGINAL