Addison's disease is a severe or total deficiency of the hormones made in the adrenal cortex, caused by a destruction of the adrenal cortex. It is a rare hormonal disorder that affects about one in 100,000 people. It occurs when the adrenal glands, located above each kidney, do not produce enough corticosteroids – in particular, the hormone cortisol, and in some cases, the hormone aldosterone. There are normally two adrenal glands, one located above each kidney. The adrenal glands are in fact two endocrine (ductless, or hormone-producing) glands in one. The inner part of the adrenal (the 'medulla') produces epinephrine (also called adrenaline) which is produced at times of stress and helps the body respond to "fight or flight" situations by raising the pulse rate, adjusting blood flow, and raising blood sugar. However, the absence of the adrenal medulla and epinephrine does not cause disease.
In contrast, the outer portion of the adrenal – the cortex – is more critical. The adrenal cortex makes two important steroid hormones, cortisol and aldosterone. Cortisol mobilizes nutrients, modifies the body's response to inflammation, stimulates the liver to raise the blood sugar, and also helps to control the amount of water in the body. Aldosterone regulates salt and water levels which affects blood volume and blood pressure. Cortisol production is regulated by another hormone, adrenocorticotrophic hormone (ACTH), made in the pituitary gland which is located just below the brain.
Secondary adrenal insufficiency, caused by a lack of ACTH, results in a deficiency of cortisol, but usually not aldosterone. The cause is either pituitary disease, such as a tumor, or the prolonged use of "steroid" medication that suppresses ACTH. The treatment is simply to replace cortisol, usually with the synthetic steroid prednisone, but sometimes hydrocortisone or cortisone acetate.
Auto-immune Addison's disease, the most common type, can be associated with other auto-immune diseases that similarly affect other endocrine glands. The most common one is the thyroid. If an underactive thyroid (hypothyroidism) coexists with Addison's disease, this is called Schmidt's syndrome. Less commonly associated auto-immune diseases are insulin-dependent diabetes mellitus, and insufficiencies of the parathyroid glands, gonads, and vitamin B12 absorption (pernicious anemia).
Classical Addison's disease, also called primary adrenal insufficiency, results from a loss of both cortisol and aldosterone secretion due to the near total or total destruction of both adrenal glands. About 70% of reported cases of primary adrenal insufficiency result from destruction of the adrenal cortex, the outer layer of the adrenal glands, by the body's own immune system.
Nowadays, the major cause of Addison's disease is an auto-immune reaction in which the body's immune system erroneously makes antibodies against the cells of the adrenal cortex and slowly destroys them. That process takes months to years.
There are also several less common causes of Addison's disease:
Other symptoms include:
Because symptoms of Addison's disease progress slowly, they may go unrecognized until a physically stressful event, such as another illness (e.g. flu), surgery or an accident, causes them to become much worse suddenly. Such an acute episode of the disease is called an Addisonian crisis. In about 25% of patients with Addison's disease, symptoms first become apparent during this type of crisis. An Addisonian crisis is considered a medical emergency because, left untreated, it can be fatal. Symptoms of an Addisonian crisis include the following:
A medical history of the symptoms mentioned above, especially hyperpigmentation of the skin or gums, is often enough to raise a strong suspicion, prompting the appropriate tests. Quite often, however, the first clue is from the abnormal results of routine tests done in a hospital or doctor's office. These may include an elevated blood level of potassium, a low blood level of sodium, a shift in the ratio of certain white blood cells, or surprising changes on an EKG or chest X-ray that are caused by high potassium or low blood volume.
Other causes for these changes, particularly from medications, must be considered first. A definitive diagnosis of Addison's disease requires that definitive tests be carried out. These tests measure the amount of cortisol and aldosterone in the blood and urine, and document a lack of the normal increase in the levels of these two hormones after administration of ACTH given by injection. An elevated blood level of ACTH should also be found. If the patient is very sick and Addison's disease is suspected, treatment can be initiated while the diagnostic tests are being done. Once the diagnosis of Addison's disease is established, an effort should be made to find the cause by checking for tuberculosis and other infections through skin tests and X-rays.
Patients with Addison's disease should be taught to treat minor illnesses with extra salt and fluids. This is especially important if fever, vomiting or diarrhea is present. Persistence of these signs requires immediate treatment in an emergency room with intravenous saline (salt water) and hydrocortisone. Since Addison's disease is a chronic condition, daily replacement medication can never be stopped.
Proper maintenance treatment requires regular visits to a physician for examinations, laboratory tests, and discussions about symptoms. Certain blood tests, including sodium, potassium, blood counts and plasma renin are very useful in monitoring the response to adjustments in dosage. There is no single blood or urine test that is sufficient by itself.
See a doctor if you notice darkening of your skin or gums, along with other symptoms of Addison's disease.