Addison’s disease is a rare but serious condition where the small adrenal glands sitting atop your kidneys stop producing essential hormones your body needs to function properly. While it affects only about 1 in 100,000 people, understanding its symptoms and getting proper treatment can make all the difference.

What Is Addison’s Disease?

Addison’s disease, also known as primary adrenal insufficiency, is a chronic condition in which your adrenal glands don’t produce enough of the hormones cortisol and aldosterone. These small, triangle-shaped glands sit on top of each of your kidneys and are part of your body’s endocrine system, the network of glands that produce hormones to regulate various bodily functions.^[1]

Cortisol is often called the stress hormone because it helps your body respond to stress from illness, injury, or surgery. But it does much more than that. Cortisol helps maintain your blood pressure, supports heart function, keeps your immune system working properly, and regulates blood sugar levels. Without adequate cortisol, your body cannot function normally, which is why this hormone is essential for life.^[1]

Aldosterone is the other crucial hormone affected by Addison’s disease. This hormone controls the balance of sodium (salt) and potassium in your blood. By doing so, it regulates how much fluid your kidneys remove as urine, which directly affects your blood volume and blood pressure. When aldosterone levels drop too low, your body struggles to maintain proper fluid balance and blood pressure.^[1]

How Common Is Addison’s Disease?

Addison’s disease is considered a rare condition. In the United States, it affects approximately 1 in 100,000 people. In Western Europe and the United States, the estimated prevalence is about one in 20,000 persons, making it uncommon enough that doctors need to maintain a high level of suspicion to avoid missing the diagnosis.^[1][12]

The disease can affect people of all age groups, but it most commonly appears in adults between the ages of 30 and 50 years old. Addison’s disease can sometimes affect children, though this is less common. The condition does not appear to have a strong preference for any particular ethnic or racial group.^[1][4]

What Causes Addison’s Disease?

The most common cause of Addison’s disease in the United States and Western Europe is an autoimmune attack. In autoimmune adrenalitis, your body’s immune system mistakenly identifies your adrenal glands as foreign invaders and destroys them. More than 90 percent of recent-onset cases show the presence of antibodies against an enzyme called 21-hydroxylase, which can appear years or even decades before symptoms begin.^[3][12]

When the immune system attacks the adrenal cortex (the outer layer of the adrenal glands), it gradually destroys the tissue responsible for producing cortisol and aldosterone. This destruction happens slowly over time, which explains why symptoms typically develop gradually rather than appearing suddenly.^[3]

While autoimmune disease is the leading cause, other factors can also damage the adrenal glands and cause Addison’s disease. Infections such as tuberculosis can destroy adrenal tissue. In some parts of the world, tuberculosis remains a significant cause of the condition. Other infections, including fungal infections, can also affect the adrenal glands.^[12]

Less common causes include bleeding into the adrenal glands (hemorrhage), cancer that has spread to the adrenal glands, certain medications, and a genetic condition called adrenoleukodystrophy. In some cases, surgical removal of the adrenal glands, radiation treatment, or physical injury to the glands can trigger the disease.^[12][16]

Who Is at Risk for Developing Addison’s Disease?

Certain people face a higher risk of developing Addison’s disease, particularly the autoimmune form. People who have autoimmune polyendocrine syndrome, a rare inherited condition where the immune system attacks multiple organs and tissues, are much more likely to develop Addison’s disease. This syndrome commonly affects mucous membranes, adrenal glands, and parathyroid glands, though it can impact other tissues and organs as well.^[1]

If you already have one autoimmune disease, your risk of developing another autoimmune condition like Addison’s disease increases. People with Type 1 diabetes, pernicious anemia, Graves’ disease, chronic thyroiditis, dermatitis herpetiformis, vitiligo, or myasthenia gravis face higher odds of developing autoimmune adrenalitis.^[1]

Signs and Symptoms of Addison’s Disease

With Addison’s disease, damage to the adrenal glands usually happens slowly over time, so symptoms tend to appear gradually. Because the symptoms can be vague and similar to many other conditions, the disease often goes undiagnosed until it becomes more severe. Symptoms can vary considerably from person to person.^[1]

The most common symptom of Addison’s disease is steadily worsening fatigue. This isn’t just ordinary tiredness that improves with rest. People with Addison’s disease often describe an overwhelming exhaustion that makes even simple daily activities feel exhausting. This extreme tiredness tends to get worse over time rather than improving.^[1][4]

A distinctive sign of Addison’s disease is the appearance of patches of darkened skin, called hyperpigmentation. These areas of darker skin typically appear around scars and in skin creases, such as on the knuckles, elbows, knees, and in the palmar creases of the hands. The gums may also become darker. This darkening happens because elevated levels of ACTH (a hormone from the pituitary gland trying to stimulate the failing adrenal glands) can stimulate pigment-producing cells in the skin. On brown or black skin, this change may be harder to notice.^[1][2]

Digestive problems are common in Addison’s disease. Many people experience abdominal pain, nausea, and vomiting. Diarrhea can occur, along with a loss of appetite that leads to unintentional weight loss. Interestingly, despite losing their appetite for most foods, people with Addison’s disease often develop strong cravings for salty foods. This happens because low aldosterone levels cause the body to lose salt.^[1][4]

Low blood pressure is another hallmark of the condition. This can cause people to feel dizzy or lightheaded, especially when standing up after sitting or lying down. This type of low blood pressure is called postural hypotension. The dizziness occurs because the body cannot adjust blood pressure properly when changing positions.^[2][4]

Muscle and joint pain are frequent complaints. People may experience muscle pain, muscle spasms, muscle weakness, or joint pain that affects their ability to move comfortably. Low blood sugar, or hypoglycemia, can also occur, leading to shakiness, sweating, and confusion.^[1]

Addison’s disease can affect mental and emotional well-being as well. Changes in mood and behavior are common, including irritability, depression, difficulty concentrating, anxiety, and poor concentration. Some people describe feeling confused or having brain fog that makes it hard to focus on tasks.^[1][4]

Women with Addison’s disease may experience additional symptoms related to hormone imbalances. These can include abnormal menstrual periods, loss of body hair, and a decreased sex drive. Dehydration is also common because the body loses its ability to retain salt and water properly.^[1]

Addisonian Crisis: A Medical Emergency

In some cases, symptoms can come on quickly and cause a life-threatening event called an addisonian crisis or acute adrenal failure. This medical emergency can be triggered by an injury, severe illness, surgery, infection, accident, or a period of intense stress. During a crisis, the body’s demand for cortisol suddenly increases, but the damaged adrenal glands cannot respond.^[1][4]

An addisonian crisis requires immediate medical attention. If left untreated, it can lead to shock, unconsciousness, stroke, cardiac arrest (when the heart suddenly stops), and death. Symptoms of an addisonian crisis include extreme weakness, sudden and severe pain in the lower back, belly, or legs, feeling restless, severe dehydration, low blood pressure, a fast heart rate, severe dizziness, severe headache, feeling very drowsy or confused, seizures, and loss of consciousness.^[1][4]

Prevention

Unfortunately, there is currently no known way to prevent Addison’s disease, particularly when it is caused by an autoimmune attack on the adrenal glands. Since the exact trigger that causes the immune system to attack the adrenal tissue remains unknown, preventive measures have not been identified.^[12]

For people who have already been diagnosed with one autoimmune condition, regular monitoring and maintaining good relationships with healthcare providers may help with early detection of Addison’s disease if it develops. Being aware of the symptoms and seeking medical attention promptly when they appear can prevent the disease from progressing to a dangerous crisis.^[12]

For people already living with Addison’s disease, preventing an adrenal crisis is crucial. This involves taking prescribed medications exactly as directed every day, never running out of medication, knowing how to adjust doses during illness or stress, carrying a steroid emergency card at all times, wearing medical alert jewelry, having an emergency injection kit available, and teaching family members or close contacts how to administer the emergency injection.^[4][15]

People with Addison’s disease should be prepared to increase their steroid medication during times of physical stress, such as when they have a fever, infection, injury, or before surgery. Healthcare providers can provide guidance on when and how to adjust medication doses. Maintaining adequate salt intake, especially during hot weather or after exercise, helps prevent complications related to low aldosterone levels.^[10][16]

How the Body Changes: Understanding the Disease Process

To understand how Addison’s disease affects the body, it helps to know what happens when the adrenal glands are destroyed. The disease develops in stages over a period of years. Initially, genetic factors may increase susceptibility, followed by an unknown event that triggers the autoimmune response. Antibodies against adrenal tissue appear long before any symptoms develop.^[12]

As destruction of the adrenal cortex progresses, the glands gradually lose their ability to produce adequate amounts of hormones. One of the first metabolic changes to occur is an increase in plasma renin level, a hormone that tries to compensate for low aldosterone. As more adrenal tissue is destroyed, the body’s response to ACTH stimulation becomes blunted, meaning the glands can no longer produce cortisol even when signaled to do so.^[12]

When cortisol levels drop too low, multiple body systems are affected. Without adequate cortisol, the body cannot properly respond to stress. Blood sugar levels may drop dangerously low because cortisol normally helps maintain glucose production. Blood pressure falls because cortisol helps maintain vascular tone and blood pressure. The immune system may not function optimally, making the body more vulnerable to infections.^[1]

The lack of aldosterone creates additional problems. Without enough aldosterone, the kidneys lose their ability to retain sodium and excrete potassium properly. As sodium is lost in the urine, water follows, leading to dehydration and low blood volume. This further contributes to low blood pressure. Meanwhile, potassium levels in the blood can rise too high, which can affect heart rhythm and muscle function.^[1]

The darkening of the skin seen in Addison’s disease occurs through a different mechanism. As the adrenal glands fail, the pituitary gland in the brain tries to stimulate them by producing more and more ACTH. Elevated ACTH levels can stimulate melanocytes (pigment-producing cells in the skin), leading to increased pigmentation, especially in areas exposed to friction or sun exposure.^[12]

During an adrenal crisis, these problems become acute and severe. The body’s demand for cortisol suddenly increases due to illness, injury, or stress, but the destroyed adrenal glands cannot respond. Blood pressure drops precipitously, blood sugar plummets, severe dehydration develops rapidly, and electrolyte imbalances become life-threatening. Without immediate treatment with intravenous fluids, salt, and high-dose steroids, organ systems can fail.^[13]