Autoimmune Addison disease

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Reviewed June 2014

What is autoimmune Addison disease?

Autoimmune Addison disease affects the function of the adrenal glands, which are small hormone-producing glands located on top of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system that attacks the adrenal glands. As a result, the production of several hormones is disrupted, which affects many body systems.

The signs and symptoms of autoimmune Addison disease can begin at any time, although they most commonly begin between ages 30 and 50. Common features of this condition include extreme tiredness (fatigue), nausea, decreased appetite, and weight loss. In addition, many affected individuals have low blood pressure (hypotension), which can lead to dizziness when standing up quickly; muscle cramps; and a craving for salty foods. A characteristic feature of autoimmune Addison disease is abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction, such as the armpits, elbows, knuckles, and palm creases. The lips and the inside lining of the mouth can also be unusually dark. Because of an imbalance of hormones involved in development of sexual characteristics, women with this condition may lose their underarm and pubic hair.

Other signs and symptoms of autoimmune Addison disease include low levels of sugar (hypoglycemia) and sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. Affected individuals may also have a shortage of red blood cells (anemia) and an increase in the number of white blood cells (lymphocytosis), particularly those known as eosinophils (eosinophilia).

Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.

Individuals with autoimmune Addison disease or their family members often have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes.

How common is autoimmune Addison disease?

Addison disease affects approximately 11 to 14 in 100,000 people of European descent. The autoimmune form of the disorder is the most common form in developed countries, accounting for up to 90 percent of cases.

What genes are related to autoimmune Addison disease?

The cause of autoimmune Addison disease is complex and not completely understood. A combination of environmental and genetic factors plays a role in the disorder, and changes in multiple genes are thought to affect the risk of developing the condition.

The genes that have been associated with autoimmune Addison disease participate in the body's immune response. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. The most well-known risk factor for autoimmune Addison disease is a variant of the HLA-DRB1 gene calledHLA-DRB1*04:04. This and other disease-associated HLA gene variants likely contribute to an inappropriate immune response that leads to autoimmune Addison disease, although the mechanism is unknown.

Normally, the immune system responds only to proteins made by foreign invaders, not to the body's own proteins. In autoimmune Addison disease, however, an immune response is triggered by a normal adrenal gland protein, typically a protein called 21-hydroxylase. This protein plays a key role in producing certain hormones in the adrenal glands. The prolonged immune attack triggered by 21-hydroxylase damages the adrenal glands (specifically the outer layers of the glands known, collectively, as the adrenal cortex), preventing hormone production. A shortage of adrenal hormones (adrenal insufficiency) disrupts several normal functions in the body, leading to hypoglycemia, hyponatremia, hypotension, muscle cramps, skin hyperpigmentation and other features of autoimmune Addison disease.

Rarely, Addison disease is not caused by an autoimmune reaction. Other causes include infections that damage the adrenal glands, such as tuberculosis, or tumors in the adrenal glands. Addison disease can also be one of several features of other genetic conditions, including X-linked adrenoleukodystrophy and autoimmune polyglandular syndrome, type 1, which are caused by mutations in other genes.

How do people inherit autoimmune Addison disease?

A predisposition to develop autoimmune Addison disease is passed through generations in families, but the inheritance pattern is unknown.

Where can I find information about diagnosis or management of autoimmune Addison disease?

These resources address the diagnosis or management of autoimmune Addison disease and may include treatment providers.

You might also find information on the diagnosis or management of autoimmune Addison disease inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about autoimmune Addison disease?

You may find the following resources about autoimmune Addison disease helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Additional NIH Resources - National Institutes of Health
National Endocrine and Metabolic Diseases Information Service: Adrenal Insufficiency and Addison's Disease
Educational resources - Information pages (8 links)
Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature

What other names do people use for autoimmune Addison disease?

autoimmune Addison's disease
autoimmune adrenalitis
classic Addison disease
primary Addison disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about autoimmune Addison disease?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding autoimmune Addison disease?

adrenal cortex ; adrenal glands ; anemia ; autoimmune ; bacteria ; diabetes ; eosinophils ; gene ; HLA ;hormone ; hyperkalemia ; hypoglycemia ; hyponatremia ; hypotension ; immune response ;immune system ; infection ; inheritance ; inheritance pattern ; kidney ; leukocyte ; potassium ;predisposition ; protein ; shock ; sodium ; surgery ; syndrome ; thyroid ; trauma ; tuberculosis ;white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (7 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.