Addison's disease, or adrenal insufficiency, occurs when the outer layer of the adrenal glands are damaged.

Most commonly, it is caused by the immune system attacking the glands as if they were harmful bacteria or viruses. However, it can be caused in other ways.

The adrenal glands, which form part of the endocrine system, are situated just above each kidney. They produce hormones that affect every organ and tissue in our bodies. The adrenal glands consist of 2 layers, the medulla (interior) and cortex (outer layer). The medulla produces adrenaline-like hormones, while the cortex secretes corticosteroids.

Fast facts on Addison's disease

Here are some key points about Addison's disease. More detail and supporting information is in the main article.

  • Addison's disease is caused by disruptions to the adrenal glands, preventing normal secretions of corticosteroids.
  • Disruptions may be caused by immune system response, genetic defects, or other conditions, including cancer.
  • The most common cause is an immune system response.

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The adrenal glands are located on top of the kidneys. They produce hormones, but when this process is disrupted, it can cause Addison's disease.

Disruptions to the hormone production of the adrenal glands cause Addison's disease. This disruption can be caused by a number of factors, including an autoimmune disorder, tuberculosis, or a genetic defect. However, approximately 80 percent of cases of Addison's disease in industrialized nations are caused by autoimmune conditions.

The adrenal glands stop producing enough steroid hormones (cortisol and aldosterone) when 90 percent of the adrenal cortex is destroyed. As soon as levels of these hormones start to drop, Addison's disease signs and symptoms begin to emerge.

The immune system is the body's defense mechanism against disease, toxins, or infection. When a person is ill, the immune system produces antibodies, which attack whatever is causing them to be ill.

Some people's immune systems may start attacking healthy tissue and organs - this is called an autoimmune disorder.

In the case of Addison's disease, the immune system attacks cells of the adrenal glands, slowly reducing how well they can function.

Addison's disease that is the result of an autoimmune condition is also known as autoimmune Addison's disease.

Genetic causes of Autoimmune Addison's Disease

Recent studies have demonstrated that some people with specific genes are more likely to have an autoimmune condition.

Although the genetics of Addison's are not fully understood, the genes most commonly associated with the condition belong to a family of genes called the human leukocyte antigen (HLA) complex. This complex helps the immune system distinguish between the body's own proteins and those made by viruses and bacteria.

Many patients with autoimmune Addison's disease have at least one other autoimmune disorder, such as hypothyroidism, type 1 diabetes, or vitiligo.

Tuberculosis (TB) is a bacterial infection that affects the lungs and can spread to other parts of the body. If the TB reaches the adrenal glands it can severely damage them, affecting their production of hormones.

Patients with TB have a higher risk of damage to the adrenal glands, making them more likely to develop Addison's disease.

In America, because TB is now less frequent, cases of Addison's disease caused by TB are uncommon. However, in countries where TB is a significant problem, there are higher rates.

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Having surgery to remove the adrenal glands may cause Addison's disease in some cases.

Addison's disease may also be caused by other factors that affect the adrenal glands:

  • a genetic defect in which the adrenal glands do not develop properly
  • a hemorrhage
  • adrenalectomy - the surgical removal of the adrenal glands
  • amyloidosis
  • an infection, such as HIV or a disseminated fungal infection
  • cancer that has metastasized to the adrenal glands

The adrenal glands can also be negatively affected if the pituitary gland becomes diseased. Normally, the pituitary produces adrenocorticotropic hormone (ACTH). This hormone stimulates the adrenal glands to produce hormones.

If the pituitary is damaged or diseased, less ACTH is produced and, consequently, less hormones are produced by the adrenal glands, even though they are not diseased themselves. This is called secondary adrenal insufficiency.

Some people taking anabolic steroids, such as bodybuilders, may increase their risk of Addison's disease. The production of hormones caused by taking steroids, particularly over a long period of time, can disrupt the adrenal glands' ability to produce healthy levels of hormones - this can increase the risk of developing the disease.

Glucocorticoids, such as cortisone, hydrocortisone, prednisone, prednisolone, and dexamethasone act like cortisol. In other words, the body believes there is an increase of cortisol and suppresses ACTH. As mentioned above, a reduction in ACTH causes less hormones to be produced by the adrenal glands.

Also, individuals who take oral corticosteroids for conditions, such as lupus or inflammatory bowel disease, and stop taking them suddenly, may experience secondary adrenal insufficiency.