Known also as adrenal insufficiency, Addison’s disease is usually an autoimmune disease caused by a faulty immune response. Infections, steroid use, and genetics can also increase risk.

Addison’s disease disrupts the production of aldosterone and cortisol, which can lead to severe complications.

There are multiple reasons why people can develop this autoimmune disease, ranging from a faulty immune response to infections, steroid use, and certain genetic factors.

Addison’s disease occurs when damage to the adrenal cortex disrupts hormone production in the adrenal glands.

About the adrenal glands

The adrenal glands are situated just above each kidney. They produce hormones that affect organs and tissues throughout the body. They are made up of an interior layer (medulla) and an outer layer (cortex), with medulla producing epinephrine-like hormones, and the cortex secreting corticosteroids.

Damage to the cortex can disrupt the production of hormones such as cortisol, aldosterone, and androgens.

Disruption to the adrenal glands can result from:

  • a faulty autoimmune response
  • genetic factors
  • injury to or bleeding in the adrenal or pituitary glands
  • conditions such as cancer, tuberculosis (TB), and HIV
  • removal of the adrenal or pituitary glands
  • chronic steroid use

In industrialized countries, 80–90% of cases result from an autoimmune disease.

Adrenal insufficiency can lead to a range of symptoms, including:

Two types of adrenal insufficiency exist.

Primary adrenal insufficiency

This condition results from direct injury to the adrenal cortex, or the outer layer of the adrenal glands.

Causes include:

  • an autoimmune disease
  • infections such as TB, cytomegalovirus, and HIV
  • bleeding in the adrenal glands due to trauma, blood clotting, or other factors
  • conditions such as hemochromatosis, cancer, and amyloidosis
  • conditions a person has from birth, such as congenital adrenal hyperplasia
  • the use of drugs that prevent the production of cortisol, including ketoconazole and etomidate

Secondary adrenal insufficiency

Indirectly, issues with the pituitary gland can also cause secondary adrenal insufficiency. The pituitary gland produces adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce other hormones.

Issues with the pituitary glands can cause them to produce less ACTH. Consequently, the adrenal glands will also produce lower levels of hormones.

Other causes of secondary adrenal insufficiency include:

  • pituitary tumors or infection
  • surgery to remove the pituitary gland
  • bleeding in the pituitary gland
  • genetic conditions that affect the pituitary gland

Using steroid drugs affects the hypothalamus and pituitary, leading to a reduction in the body’s cortisol production and secondary adrenal insufficiency.

The immune system defends the body from disease, toxins, and infection. That is why someone with another autoimmune condition may be more likely to develop autoimmune Addison’s disease if they already have one of the following conditions:

People with certain genetic features and conditions have a higher risk of adrenal insufficiency.

These include:

  • congenital adrenal hyperplasia, a group of disorders that affect cortisol production
  • adrenal leukodystrophy, which affects the adrenal glands, the brain, and the myelin sheath, which protects the nerves
  • Wolman disease, which causes calcification of the adrenal glands
  • antiphospholipid syndrome (APS)

The genes most likely linked to autoimmune Addison’s disease are within the human leukocyte antigen complex. This genetic complex helps the immune system distinguish between the body’s own proteins and those made by viruses and bacteria.

Bleeding into the adrenal glands, which health experts also call adrenal hemorrhage, can result from:

Cancer can cause symptoms of Addison’s disease in the following ways:

  • tumors developing in the adrenal glands
  • metastasis, when cancer spreads to the adrenal glands from another area
  • lymphoma developing

Researchers are also investigating whether some drugs used in cancer treatment, such as steroids with chemotherapy, may increase the risk of fatigue due to adrenal insufficiency.

Other conditions that may lead to Addison’s disease include:

  • amyloidosis, which occurs when too much amyloid protein builds up in the body
  • sarcoidosis, when small patches of inflamed tissue, or granulomas, develop in the body’s organs
  • hemochromatosis, when too much iron builds up in the body

Hemochromatosis is an infiltrative condition. It infiltrates the adrenal glands substances that are harmful to the glands, namely iron.

Infections that can increase the risk of Addison’s disease include:

These infections can damage the adrenal glands and affect the production of hormones.

Some people have surgery to remove the adrenal glands, called adrenalectomy.

A doctor may recommend this if:

  • there is cancer in the adrenal glands
  • cancer has spread, for example, from the kidneys
  • the glands are overproducing hormones, as in Conn’s syndrome or Cushing’s syndrome
  • there is a change in size in the glands

If the surgeon removes both adrenal glands, the person may need medication for the rest of their life to make up for the loss of hormone production.

Surgery to remove the pituitary gland can also impact hormone production in the adrenal glands.

People take steroids for various conditions, as they help manage inflammation. However, long-term use can disrupt hormone production in the adrenal glands and increase the risk of secondary insufficiency.

Glucocorticoids — such as cortisone, hydrocortisone, prednisone, and dexamethasone — act like cortisol. When a person takes them, the body perceives an increase in cortisol and produces less ACTH. As a result, the adrenal glands produce lower levels of hormones.

Stopping oral corticosteroids suddenly can lead to adrenal insufficiency. A doctor will gradually reduce the dose over several weeks or months to allow the adrenal glands to work properly again.

Adrenal insufficiency can also occur after effective treatment for Cushing’s syndrome. In this condition, a person’s body produces too much cortisol. Treatment reduces cortisol levels but can disrupt the function of the adrenal glands for a while.

Changes in hormone levels usually happen over time, and a person may not notice any difference.

However, when damage affects 90% of the adrenal cortex, the body will no longer be able to produce aldosterone or cortisol, and symptoms will start to appear.

As symptoms progress, a crisis may develop, which health experts call an Addisonian or acute adrenal crisis.

It can happen suddenly and can be life threatening. It is a medical emergency.

Symptoms include:

Tests may show:

Factors that can trigger a crisis include:

  • high stress levels
  • infection
  • trauma or injury
  • surgery
  • diarrhea and vomiting

For this reason, it is essential to seek prompt advice if anyone experiences symptoms that could indicate adrenal insufficiency.

When to seek medical help

Anyone who believes they have symptoms of Addison’s disease — such as weakness, fatigue, and unintentional weight loss — should seek medical help.

Seeking treatment when symptoms first appear may help reduce the risk of an Addisonian crisis.

Addison’s disease, or adrenal insufficiency, occurs when the adrenal glands no longer produce hormones effectively.

The main cause of adrenal insufficiency is a faulty autoimmune response. Other causes include injury, steroid use, and conditions such as cancer, HIV, and TB.

Symptoms include fatigue and weight loss, but they may not appear until a later stage, as the progression is gradual.

In time, however, an Addisonian crisis can develop, where symptoms suddenly become severe. This is potentially life threatening.