Addison's disease, also called adrenal insufficiency or hypocortisolism, is a rare endocrine (hormonal) disorder that is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and occasional darkening of the skin.
Addison's disease is named after Dr. Thomas Addison, who first identified adrenal insufficiency in 1849. The disease occurs when the adrenal glands do not produce enough of the hormone cortisol and, in some cases, the hormone aldosterone.
The adrenal glands, located just above each of the two kidneys, secrete cortisol, also called hydrocortisone. Cortisol regulates proper glucose metabolism, blood pressure, and insulin release for blood sugar maintenance and it is involved in the inflammatory response. When the adrenal glands do not produce enough cortisol, symptoms of Addison's disease develop.
Aldosterone belongs to a class of hormones called mineralocorticoids. This hormone helps regulate blood pressure as well as the water and salt balance in the body by helping the kidneys retain sodium and expel potassium. When aldosterone production falls too low, the kidneys are not able to regulate the salt and water balance, subsequently causing blood volume and blood pressure to drop.
Addison's disease can occur at any age, but is most common in people ages 30 to 50. Researchers estimate that about one out of 100,000 people have Addison's disease. The disease is slightly more common in females than men. Researchers estimate that the male to female ratio is about 1:1.5-3.5
Treatment for Addison's involves replacing the hormones that the adrenal glands are not producing with medication. Corticosteroids like hydrocortisone (A-hydroCort®, Cortef®, Hydrocortone®, Hydrocortone® Acetate, Hydrocortone® Phosphate, Solu-Cortef®) are used to replace cortisol. Mineralocorticoids like fludrocortisone (Florinef®) are used to replace aldosterone.
Primary adrenal insufficiency: Addison's disease can be caused by a primary adrenal insufficiency. This type of deficiency occurs when the adrenal cortex is damaged and does not produce enough cortisol. Adrenal insufficiency occurs when at least 90% of the adrenal cortex (outer layer of the adrenal glands) has been destroyed. Several conditions, including autoimmunity, polyendocrine deficiency syndrome, and tuberculosis infection, can lead to primary adrenal insufficiency.
Autoimmune disorders that lead to the gradual destruction of the adrenal cortex are responsible for about 70% of Addison's disease cases. Autoimmune disorders occur when the immune system mistakenly attacks the body's cells because they are identified as foreign cells. The body tries to destroy healthy tissue because the immune system identifies the cells as harmful invaders like bacteria. As a result, often both cortisol and aldostertone hormones are deficient. Sometimes only the adrenal glands are affected, and sometimes other glands (like the pituitary gland) are also affected.
The polyendocrine deficiency syndrome is another type of primary adrenal insufficiency that may also lead to Addison's disease. This occurs when other organs, in addition to the adrenal glands, do not secrete enough hormones, including cortisol. There are two forms of polyendocrine deficiency -
type I and type II (Schmidt's disease).
Type I occurs in children and adrenal insufficiency may be accompanied by underactive parathyroid glands (glands in front of the neck that regulate calcium in the blood), slow sexual development, pernicious anemia (low levels of red blood cells caused by inability to absorb vitamin B12), chronic candida infections (yeast infections), chronic active hepatitis (liver infection), and hair loss (very rare).
Type II, commonly called Schmidt's syndrome, typically affects young adults. Common symptoms of type II polyendocrine deficiency syndrome may include slow sexual development, diabetes, and vitiligo (white patches of skin). Some patients may have an underactive thyroid, which often causes symptoms such as fatigue, sensitivity to cold, coarse and thinning hair, brittle nails, sore muscles, depression, weight gain, constipation, and/or heavy or irregular menstrual periods.
Tuberculosis (TB), a bacterial infection of the lungs that can spread to the adrenal glands, accounts for about 20% of cases of primary adrenal insufficiency in developed countries, such as the United States.
Less common causes of primary adrenal insufficiency, which can lead to Addison's disease, include chronic infection (usually fungal infections), cancer cells spreading from other parts of the body to the adrenal glands, amyloidosis (disease that causes an abnormal protein to build up in the body's tissues and organs), and surgical removal of the adrenal glands.
Secondary adrenal insufficiency: Secondary adrenal insufficiency occurs when the adrenal glands are healthy, but factors outside of the adrenal glands stimulate them to produce less cortisol. The most common cause of secondary adrenal insufficiency occurs when patients who are taking cortisol-like drugs (corticosteroids) for chronic conditions like asthma or arthritis suddenly stop taking the medication. These drugs, which can be inhaled or taken orally or intravenously (injected into the vein), suppress the hypothalamic corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). CRH stimulates the release of ACTH, which then stimulates the adrenal glands to release cortisol hormones. Prolonged suppression of the adrenal glands can lead to atrophy (shrinkage) and it may take several weeks to months for the patient to recover to full function after the drug is discontinued. Therefore, patients should slowly taper off the mediation under the supervision of their healthcare providers.
Secondary adrenal insufficiency can also occur if the pituitary gland does not produce adequate amounts of ACTH, the chemical that signals the adrenal glands to release cortisol. Consequently, individuals who have low levels of ACTH will also have low levels of cortisol, even if the adrenal glands are healthy.
Stress: Patients who have untreated Addison's disease may experience Addisonian crisis, also known as acute adrenal failure, in response to physical stress, such as an injury, infection, or illness. This is a serious condition that can be life threatening.
Symptoms are the same for primary and secondary adrenal insufficiency that cause Addison's disease. Symptoms typically develop slowly, often over several months. Physical stress, such as injury, infection, or illness, can cause symptoms to appear suddenly. Common symptoms include muscle weakness and fatigue, weight loss and decreased appetite, darkening of the skin, low blood pressure, fainting, cravings for salt, low blood sugar levels, irritability, depression, diarrhea, nausea, and vomiting.
Symptoms of acute adrenal failure (Addisonian crisis) may also include lower back pain, abdominal pain, leg pain, low blood pressure, loss of consciousness, and severe vomiting and diarrhea that can lead to dehydration.
General: If it is suspected that a patient has Addison's disease, a healthcare provider may measure the cortisol levels of the patient's blood in the morning (usually between 6 and 8:00 a.m.). Healthy individuals typically have plasma cortisol levels that range from 5-23 micrograms/deciliter. Plasma cortisol levels less than 10 micrograms/deciliter are suggestive of Addison's disease.
However, the standard diagnostic test for Addison's disease is the adrenocorticotropic hormone (ACTH) stimulation test. If a patient tests positive for Addison's disease, a healthcare provider may then perform a corticotropin releasing hormone (CRH) stimulation test and/or imaging studies (scans that take pictures of the body's internal organs) to determine the cause of the disease.
Adrenocorticotropic hormone(ACTH) stimulation test: The adrenocorticotropic hormone (ACTH) test measures the level of cortisol in the blood and urine before and 30-60 minutes after an injection of man-made ACTH. Individuals who do not have adrenal damage will begin producing cortisol in response to the injection. Patients with Addison's disease will produce minimal or no cortisol in response to the injection.
Corticotropin releasing hormone (CRH) stimulation test: If the patient tests positive to the ACTH test, a corticotropin releasing hormone (CRH) stimulation test is conducted to determine the cause of adrenal insufficiency. The patient's cortisol levels are measured in the urine and blood before the test. Then, a man-made CRH is injected intravenously into the patient. Cortisol levels in the blood and urine are then measured 30, 60, 90, and 120 minutes after the injection. Patients with primary adrenal insufficiency have high levels of ACTH but do not produce cortisol. Patients with secondary adrenal insufficiency have will have very low cortisol levels in response to the injection and absent or delayed ACTH responses. Absent ACTH response indicate that the pituitary gland is causing the disease. A delayed ACTH response indicates that the hypothalamus (part of the brain that controls the release of hormones from the pituitary gland) is the cause.
Imaging tests: Imaging studies, including computerized tomography (CT) and magnetic resonance imaging (MRI) scans, may be conducted at the hospital after a patient shows low levels of cortisol in response to the ACTH stimulation test. During these procedures, which are generally noninvasive and painless, pictures of the internal organs are taken with machines that use X-rays and magnetic waves. The healthcare provider will check the size of the adrenal glands and pituitary glands. If the adrenal glands are smaller than normal, this indicates that primary adrenal insufficiency is the cause. If the pituitary gland is smaller than normal, this indicates that secondary adrenal insufficiency is the cause.
General: Since patients with Addison's disease do not produce enough hormones, treatment may include one or more hormones to replace the deficiency. Corticosteroids like hydrocortisone are used to replace cortisol. Mineralocorticoids like fludrocortisone (Florinef®) are used to replace aldosterone.
When signs and symptoms of the disease begin to subside, this indicates that the treatment is working. However, it can be challenging to obtain the appropriate dosing for the patient. If the dose is too low, the patient will experience continued adrenal insufficiency. Children may suffer from nocturnal hypoglycemia (low blood sugar levels at night), which can result in seizures. If the dose is too high, patients may experience weight gain, increased blood pressure, and osteoporosis (hollow, brittle bones).
Corticosteroids: Corticosteroids, such as hydrocotisone (Cortef® or Hydrocortone®), prednisone, cortisone, and dexamethasone (Decadron® Baldex® or Dexone®), are used to replace low levels of cortisol. These medications are taken once or twice a day to control hormone levels. Corticosteroids may increase blood glucose levels and should be used cautiously in diabetics.
Mineralocorticoids: Patients who also have low levels of aldosterone typically receive daily doses of fludrocortisone acetate (Florinef®). Patients with secondary adrenal insufficiency normally maintain aldosterone production, so they do not need aldosterone replacement therapy.
Emergency care: An Addisonian crisis (acute adrenal failure) is a life-threatening condition that causes low blood pressure, low blood sugar levels, and high levels of potassium in the blood. This condition requires immediate medical care. Treatment generally includes intravenous injections of hydrocortisone, saline solution, or sugar (dextrose).
Management: Patients should consider carrying a medical alert card and/or wearing a medical alert bracelet. Patients should carry extra medication with them because missing even one dose of medication may cause symptoms to return.
Some healthcare providers may prescribe an injectable form of corticosteroids for patients to carry with them, in case of an emergency.
Since stress can exacerbate symptoms of Addison's disease, patients should find ways to manage their stress. Patients should maintain a positive outlook and avoid triggers of stress. Regular exercise may help decrease stress levels. Also, good scientific evidence suggests that music therapy, aromatherapy, art therapy, relaxation therapy, and yoga may help relieve symptoms of stress. Patients may also benefit from classes that teach individuals how to manage their time, stress, and anger.
Patients with Addison's disease should visit their healthcare providers regularly to monitor their hormone levels.
DHEA: DHEA (dehydroepiandrosterone) is a hormone that is produced by the adrenal glands. Several studies suggest that DHEA may improve well-being, quality of life, exercise capacity, sex drive, and hormone levels in people with adrenal insufficiency. Though promising, additional study is needed to make a strong recommendation. Adrenal insufficiency is a serious medical condition and should be treated under the supervision of a qualified health care professional, including a pharmacist.
Avoid if allergic to DHEA. Avoid with a history of seizures. Use with cautiously with adrenal or thyroid disorders. Use cautiously if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizures, or stroke. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risk. Avoid if pregnant or breastfeeding.
Unclear or conflicting scientific evidence:
Licorice: Licorice is harvested from the root and dried rhizomes of the low-growing shrub Glycyrrhiza glabra. Licorice has been used historically for adrenal insufficiency. In theory, there may be some benefits of licorice for high potassium levels resulting from abnormally low aldosterone levels. There is early evidence in humans in support of this use. However, research is preliminary and a qualified healthcare provider should supervise treatment.
Avoid licorice if allergic to licorice, any component of licorice, or any member of the Fabaceae (Leguminosae) plant family. Avoid with congestive heart failure, coronary heart disease, kidney disease, liver disease, fluid retention, high blood pressure, or hormonal abnormalities. Avoid if taking diuretics. Licorice can cause abnormally low testosterone levels in men or high prolactin or estrogen levels in women. This may make it difficult to become pregnant and may cause menstrual abnormalities.
Traditional or theoretical uses lacking sufficient evidence:
Astragalus: Preliminary research reports that Astragalus containing herbal formulas may protect adrenal function, however the effect of Astragalus on adrenal insufficiency is currently unknown. Additional research is needed.
Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant or autoimmune diseases (like HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
Ginseng: Ginseng has been traditionally used as an adrenal tonic, and in laboratory study has demonstrated adrenal stimulating effects. High quality clinical study is warranted to better understand ginseng's effect on adrenal function.
Avoid ginseng with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.
Patients who are taking corticosteroids should not discontinue medication abruptly. Instead, patients should slowly taper off the medication under the supervision of their healthcare providers.
Patients can take precautions to avoid contracting infections that may lead to secondary adrenal insufficiency. Avoiding close contact with individuals who have contagious illnesses may help reduce the risk of acquiring infections.
Practicing good hygiene and regularly washing the hands with soap and water may also help reduce the risk of acquiring infections.
Since stress can exacerbate symptoms of Addison's disease, patients should find ways to manage their stress. Patients should maintain a positive outlook and avoid triggers of stress. Regular exercise may help decrease stress levels. Also, good scientific evidence suggests that music therapy, aromatherapy, art therapy, relaxation therapy and yoga may help relieve symptoms of stress. Patients may also benefit from classes that teach individuals how to manage their time, stress, and anger.
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.