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Disease Profile

Addison’s disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

E27.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Addison disease; Adrenal hypoplasia; Hypoadrenocorticism familial;

Categories

Autoimmune / Autoinflammatory diseases; Congenital and Genetic Diseases; Endocrine Diseases;

Summary

Addison's disease occurs when the adrenal glands do not produce enough (or any) of the hormones, cortisol and aldosterone. These adrenal gland hormones are necessary for balancing water and energy in the body. Symptoms usually develop slowly over time, and may include fatigue, loss of appetite, abdominal pain, and dark patches of skin. Sometimes symptoms occur suddenly causing a life-threatening condition called acute adrenal failure, also known as an acute adrenal crisis. Symptoms of an acute adrenal crisis include sudden weakness, pain, and fainting. The most common cause of Addison's disease is an abnormal response of the body’s immune system. Injury to the adrenal gland can also cause Addison's disease. Diagnosis is based on the the symptoms, blood and urine tests that evaluate adrenal function, and imaging studies. Treatment is focused on managing the symptoms and includes daily medications that replace the adrenal hormones. Treatment for an adrenal crisis may include intravenous hydrocortisone, fluids, and electrolytes, as well as drugs that normalize blood pressure.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Addison's disease. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms may include:[2][3][4]

  • Fatigue
  • Loss of appetite
  • Abdominal pain
  • Mood or behavior changes
  • Dark patches of skin (hyperpigmentation)
  • Muscle weakness or pain
  • Dehydration
  • Low blood pressure

Symptoms typically start in the late teens or early twenties. An acute adrenal crisis can develop in response to stress. This is a medical emergency which can lead to shock or kidney failure if not treated promptly. Symptoms of a crisis include sudden weakness, severe pain, vomiting, diarrhea, and low blood pressure which can lead to fainting. With treatment, this condition does not change over time and the symptoms can be managed.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Decreased circulating cortisol level
Low blood cortisol level
0008163
80%-99% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Anorexia
0002039
Constipation
0002019
Diarrhea
Watery stool
0002014
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fatigue
Tired
Tiredness

[ more ]

0012378
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Increased circulating ACTH level
High blood corticotropin levels
0003154
Muscle weakness
Muscular weakness
0001324
Nausea and vomiting
0002017
Weight loss
0001824
30%-79% of people have these symptoms
Androgen insufficiency
0008226
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased urinary potassium
0012364
Hyperkalemia
Elevated serum potassium levels
0002153
Hyperkalemic metabolic acidosis
0005976
Hyperuricemia
High blood uric acid level
0002149
Hyponatremia
Low blood sodium levels
0002902
Increased circulating renin level
Elevated blood renin level
0000848
Normocytic anemia
0001897
Renal salt wasting
Loss of salt in urine
0000127
5%-29% of people have these symptoms
Adrenal calcification
0010512
Adrenal hypoplasia
Small adrenal glands
0000835
Arthralgia
Joint pain
0002829
Celiac disease
0002608
Decreased female libido
Decreased female sex drive
0030018
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Dry skin
0000958
Generalized bone demineralization
0006462
Hashimoto thyroiditis
0000872
Hypercalcemia
High blood calcium levels
Increased calcium in blood

[ more ]

0003072
Hypoglycemia
Low blood sugar
0001943
Hypoparathyroidism
Decreased parathyroid hormone secretion
0000829
Orthostatic hypotension
Decrease in blood pressure upon standing up
0001278
Premature ovarian insufficiency
Early menopause
Premature menopause
Premature ovarian failure

[ more ]

0008209
Salt craving
0030083
Seizure
0001250
Sparse axillary hair
Limited armpit hair
Little underarm hair

[ more ]

0002215
Type I diabetes mellitus
Type 1 diabetes
Type I diabetes

[ more ]

0100651
Vertigo
Dizzy spell
0002321
Vitiligo
Blotchy loss of skin color
0001045
1%-4% of people have these symptoms
Primary testicular failure
0008720
Thiamine-responsive megaloblastic anemia
0004860
Thymoma
0100522
Percent of people who have these symptoms is not available through HPO
Abnormality of skin pigmentation
Abnormal pigmentation
Abnormal skin color
Abnormal skin pigmentation
Abnormality of pigmentation
Pigmentary changes
Pigmentary skin changes
Pigmentation anomaly

[ more ]

0001000
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Adrenal insufficiency
0000846
Apnea
0002104
Autosomal recessive inheritance
0000007
Cyanosis
Blue discoloration of the skin
0000961
Feeding difficulties in infancy
0008872
Vomiting
Throwing up
0002013

Cause

In most cases, Addison's disease is caused by an autoimmune reaction that leads to damage to the adrenal cortex (the outer part of the adrenal gland). Less common causes of Addison's disease include repeated infections (such as fungal infections, tuberculosis, or HIV), cancer that spreads to the adrenal glands, trauma, and amyloidosis. Rarely, Addison’s disease runs in families and may be due to a genetic predisposition.[2]

Diagnosis

Addison's disease is diagnosed based on symptoms, a clinical exam, and laboratory tests that evaluate adrenal function. In addition, imaging studies such as a chest X-ray and/or a CT scan may be used to look at the size and characteristics of the adrenal gland.[3][4]

Treatment

Treatment for Addison's disease is focused on managing the symptoms. Treatment may include daily medicines that replace the adrenal hormones. Treatment for an adrenal crisis may include intravenous hydrocortisone, fluids, and electrolytes, as well as drugs that normalize blood pressure. People with Addison's disease should carry a medical ID that states the disease and emergency instructions.[2][3]

Specialists involved in the care of someone with Addison's disease may include:

  • Endocrinologist
  • Radiologist
  • Immunologist

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Merck Manual for health care professionals provides information on Addison's disease.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Addison's disease. Click on the link to view a sample search on this topic.

          References

          1. Addison’s Disease. National Organization for Rare Disorders (NORD). 2018; https://rarediseases.org/rare-diseases/addisons-disease/#supporting-organizations.
          2. Barthel A, Benker G, Berens K, et al. An Update on Addison's disease. Exp Clin Endocrinol Diabetes. 2019; 127(2-03):165-175. https://pubmed.ncbi.nlm.nih.gov/30562824.
          3. Munir S, Waseem M. Addison Disease. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing. July 2020; https://pubmed.ncbi.nlm.nih.gov/28723023.
          4. Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults. J Endocrinol Invest. 2019; 42(12):1407-1433. https://pubmed.ncbi.nlm.nih.gov/31321757.
          5. Betterle C, Garelli S, Presotto F, Furmaniak J. From Appearance of Adrenal Autoantibodies to Clinical Symptoms of Addison's Disease: Natural History. Front Horm Res. 2016; 46:133-145.

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