What is it?
Addison’s disease is also known as primary hypoadrenalism. It occurs when the adrenal glands stop producing sufficient amounts of the hormones cortisol and aldosterone. The adrenal glands are small organs that lie on top of the kidneys. The adrenal glands, together with the hypothalamus and pituitary glands in the brain, control many systems in the body. Disruption of this hormonal system can cause severe illness.
Addison’s disease is a rare condition affecting between 1 and 4 people per 100,000. It affects males and females of all ages. However, in general it affects women more commonly than men. Most of the adrenal gland (as much as 90%) is often destroyed before symptoms appear. When diagnosed it can be easily treated but without treatment the patient may die.
There are a number of causes of Addison’s disease:
In the Western world the most common cause (about 75%) is when the body starts to produce antibodies that attack the adrenal gland, an autoimmune disorder. Usually it is the outer part of the adrenal gland, the adrenal cortex that is affected. This means that the adrenal produces little or no steroid hormones like cortisol and aldosterone. Sometimes other hormone producing glands, most commonly the thyroid gland, are affected as well.
The next most common cause, and the most common cause worldwide, is infection. Infections include tuberculosis and some fungal infections, and failure of the adrenals may also occur in Acquired Immunodeficiency Syndrome (AIDS). Other causes are very rare and include tumours, bleeding (haemorrhage), bacterial, fungal and viral infections and surgery. A genetic cause is extremely rare.
Sometimes the adrenal gland produces little or no cortisol because the pituitary gland is diseased. The pituitary gland produces ACTH that stimulates the adrenal to produce cortisol. When the pituitary gland stops stimulating the adrenal gland to produce cortisol the condition is called secondary hypoadrenalism. In this situation the production of aldosterone by the adrenal is not affected.
Often the disease changes very slowly and can be difficult to diagnose because the symptoms such as tiredness, loss of energy, weight loss and nausea are very common. One very distinctive feature in some patients with pituitary disease producing too much ACTH is the presence of darkening (pigmentation) of some areas of the skin. This darkening occurs on areas like the hands that are exposed to sun but also in the lining of the mouth, the lines or creases on the inside of the hands and any recent scars.
The most common symptoms are:
- Weakness
- Tiredness
- Not eating
- Nausea
- Weight loss
- Darkened skin
- Low blood pressure, particularly on standing up (called postural or orthostatic hypotension), causing dizziness and fainting.
Addisonian crisis
This is when symptoms are severe and appear suddenly. The patient has very low blood pressure (hypotension), feels sick (nausea), vomits, has tummy (abdominal) pain and often fever without obvious cause. This is a dangerous situation and treatment with cortisol must be given immediately after taking a blood sample. Addisonian crisis can occur if there is a haemorrhage (bleed) in the adrenal glands or it can be triggered by a stressful event, including trauma, surgery or infection.
A patient presenting with non-specific symptoms, such as tiredness and nausea, will have a blood sample taken for a general biochemical and haematological screen plus some hormone tests.
A Cortisol test may be requested when Addison’s disease is suspected but this alone may be unhelpful. If the cortisol result is inappropriately low it suggests adrenal failure. Cortisol can then be measured as part of a stimulation test to clarify the diagnosis.
An ACTH (Adrenocorticotrophic Hormone) test may be requested in Addison's disease where the concentrations of this hormone in the bloodstream are usually high. In such patients a synacthen test (stimulation test) should be carried out.
Synacthen is a drug with the partial structure of ACTH that has the actions of ACTH , the natural hormone produced by the pituitary gland. Synacthen is given by injection to see if this stimulates the adrenal glands to produce cortisol. A blood sample is taken from the forearm to measure the unstimulated (before the synacthen is given) cortisol concentration and sometimes aldosterone and plasma renin activity. Synacthen is then given by injection. After 30 minutes another blood sample is taken to see if cortisol and aldosterone levels have increased. A further sample at 60 minutes may sometimes also taken (usually in children). The timing and numbers of samples varies between hospitals. In Addison’s disease cortisol and aldosterone levels do not increase following the administration of synacthen.
Plasma renin is a substance in the blood that stimulates aldosterone release from the adrenal and the activity or concentration will be high in patients with Addison’s disease.
Electrolytes (e.g. sodium, potassium) are routinely measured in blood samples and a low sodium and high potassium concentration together with hypotension is suggestive of adrenal hypofunction.
Glucose, urea and creatinine are measured in blood samples to examine glucose levels (‘blood sugar’), kidney function and hydration status. Along with the measurement of electrolytes, these are used to monitor the response to treatment.
Tests for adrenal antibodies are sometimes requested as part of the diagnostic process when autoimmune Addison’s disease is suspected. A positive result is helpful in the diagnosis of autoimmune Addison's disease but many patients with this form of the disease have a negative result.
Non-laboratory tests
X-rays may be used to see if the adrenal glands have accumulated any calcium deposits that can occur with a tuberculosis infection.
CT (computerised tomography) or MRI (magnetic resonance imaging) scans of the abdomen and head, are used to look at the size and shape of the adrenal glands and the pituitary respectively. The adrenal glands can be enlarged with infections and cancers. With autoimmune diseases the adrenal glands are often normal or small in size.
There is no cure for failure or destruction of the adrenal glands. However, synthetic hormones (hydrocortisone and fludrocortisone) are given to mimic the action of cortisol and aldosterone respectively. This is usually in tablet form, taken 2-3 times per day. The doctor will take blood tests and check blood pressure in the early stages while the correct doses of these preparations are established. The patient will then be able to lead a healthy and relatively normal life.
Patients will often be advised to wear a Medic Alert bracelet or necklace. People with Addison’s disease are unable to produce cortisol in response to stress e.g. following a serious accident, and these Alert measures will enable medical personnel to ensure hydrocortisone is administered quickly.
Emergency treatment will be required if patients go into an Addisonian crisis. Often the patient or a family member will be trained to administer a hydrocortisone injection to allow treatment before the emergency services arrive.