Adrenal Insufficiency and Addisons Disease


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Adrenal Insufficiency and Addisons Disease

  1. 1. Adrenal Insufficiency and Addison’s Disease National Endocrine and Metabolic Diseases Information Service What is adrenal • slow the immune system’s inflammatory response insufficiency? • maintain levels of glucose—a form of sugar Adrenal insufficiency is an endocrine—or used for energy—in the blood hormonal—disorder that occurs when the adrenal U.S. Department of Health and glands do not produce enough of certain hor- • regulate the metabolism of proteins, carbo- Human Services mones. The adrenal glands are located just above hydrates, and fats the kidneys. Adrenal insufficiency can be primary The amount of cortisol produced by the adrenals NATIONAL or secondary. INSTITUTES is precisely balanced. Like many other hormones, OF HEALTH Primary adrenal insufficiency, also called Addi- cortisol is regulated by the brain’s hypothalamus son’s disease, occurs when the adrenal glands and the pituitary gland. First, the hypothalamus are damaged and cannot produce enough of the releases a “trigger” hormone called corticotropin- hormone cortisol and often the hormone aldos- releasing hormone (CRH) that signals the pitui- terone. Addison’s disease affects one to four of tary gland. The pituitary responds by sending every 100,000 people, in all age groups and both out ACTH, which in turn stimulates the adrenal sexes.1 glands. The adrenal glands respond by producing cortisol. Completing the cycle, cortisol then sig- Secondary adrenal insufficiency occurs when the nals back to both the pituitary and hypothalamus pituitary gland—a bean-sized organ in the brain— to decrease these trigger hormones. fails to produce enough adrenocorticotropin (ACTH), a hormone that stimulates the adrenal glands to produce cortisol. If ACTH output is too low, cortisol production drops. Eventually, the Hypothalamus adrenal glands can shrink due to lack of ACTH Pituitary stimulation. Secondary adrenal insufficiency is CRH much more common than Addison’s disease. ACTH What do adrenal hormones do? Cortisol Adrenal glands Cortisol belongs to a class of hormones called glucocorticoids, which affect almost every organ Cortisol and tissue in the body. Cortisol’s most important job is to help the body respond to stress. Among its many vital tasks, cortisol helps • maintain blood pressure and cardiovascular function Kidneys The hypothalamus sends CRH to the pituitary, which responds by sending out ACTH. ACTH then causes 1MunverR, Volfson IA. Adrenal insufficiency: diagnosis the adrenals to release cortisol into the bloodstream. and management. Current Urology Reports. 2006;7:80–85.
  2. 2. Aldosterone Hyperpigmentation, or darkening of the skin, can occur in Addison’s disease but not in secondary Aldosterone belongs to a class of hormones adrenal insufficiency. This darkening is most called mineralocorticoids, also produced by the visible on scars; skin folds; pressure points such adrenal glands. Aldosterone helps maintain as the elbows, knees, knuckles, and toes; lips; blood pressure and water and salt balance in the and mucous membranes such as the lining of the body by helping the kidneys retain sodium and cheek. excrete potassium. When aldosterone produc­ tion falls too low, the kidneys are not able to Because the symptoms progress slowly, they regulate water and salt balance, leading to a drop are often ignored until a stressful event like an in both blood volume and blood pressure. illness or accident causes them to worsen. Sud­ den, severe worsening of symptoms is called an What are the symptoms of Addisonian crisis, or acute adrenal insufficiency. In most cases, symptoms of adrenal insufficiency adrenal insufficiency? become serious enough that people seek medi­ The symptoms of adrenal insufficiency usually cal treatment before a crisis occurs. However, begin gradually. The most common symptoms are sometimes symptoms first appear during an • chronic, worsening fatigue Addisonian crisis. • muscle weakness Symptoms of an Addisonian or “adrenal” crisis include • loss of appetite • sudden, penetrating pain in the lower back, • weight loss abdomen, or legs Other symptoms can include • severe vomiting and diarrhea • nausea • dehydration • vomiting • low blood pressure • diarrhea • loss of consciousness • low blood pressure that falls further when If not treated, an Addisonian crisis can be fatal. standing, causing dizziness or fainting • irritability and depression What causes Addison’s • a craving for salty foods due to salt loss disease? • hypoglycemia, or low blood glucose Autoimmune Disorders • headache The gradual destruction of the adrenal cortex, the outer layer of the adrenal glands, by the • sweating body’s immune system causes up to 80 percent • in women, irregular or absent menstrual of Addison’s disease cases.2 In autoimmune periods disorders, the immune system makes antibodies that attack the body’s own tissues or organs and slowly destroy them. 2MartorellPM, Roep BO, Smit JWA. Autoimmunity in Addison’s disease. The Netherlands Journal of Medicine. 2002;60(7):269–275. 2 Adrenal Insufficiency and Addison’s Disease
  3. 3. Adrenal insufficiency occurs when at least Other Causes 90 percent of the adrenal cortex has been Less common causes of Addison’s disease are destroyed. As a result, often both cortisol and aldosterone are lacking. Sometimes only the • chronic infection, mainly fungal infections adrenal glands are affected. Sometimes other • cancer cells spreading from other parts of endocrine glands are affected as well, as in poly- the body to the adrenal glands endocrine deficiency syndrome. • amyloidosis, a disease that causes abnormal Polyendocrine deficiency syndrome is classified protein buildup in, and damage to, various into two separate forms, type 1 and type 2. Type 1 organs is inherited and occurs in children. In addition to adrenal insufficiency, these children may have • surgical removal of the adrenal glands • underactive parathyroid glands, which pro­ • AIDS-associated infections duce a hormone that regulates calcium and • bleeding into the adrenal glands phosphorus balance in the body • genetic defects including abnormal adrenal • slow sexual development gland development, an inability of the adre­ • pernicious anemia, a severe type of anemia nal gland to respond to ACTH, or a defect in adrenal hormone production • chronic candida infections, a type of fungal infection What causes secondary • chronic active hepatitis, a liver disease adrenal insufficiency? Type 2, sometimes called Schmidt’s syndrome, Secondary adrenal insufficiency can be traced to usually affects young adults and may include a lack of ACTH. Without ACTH to stimulate • an underactive thyroid gland, which pro­ the adrenal glands, the adrenals’ production of duces hormones that regulate metabolism cortisol drops. Aldosterone production is not usually affected. • slow sexual development A temporary form of secondary adrenal insuf­ • diabetes ficiency may occur when a person who has been • vitiligo, a loss of pigment on areas of the taking a synthetic glucocorticoid hormone such skin as prednisone for a long time stops taking the medication, either abruptly or gradually. Glu­ Scientists think type 2 polyendocrine deficiency cocorticoid hormones, which are often used to syndrome is also inherited because often more treat inflammatory illnesses such as rheumatoid than one family member has one or more endo­ arthritis, asthma, and ulcerative colitis, block the crine deficiencies. release of both CRH and ACTH. As a result, Tuberculosis the adrenals may begin to atrophy—or shrink— from lack of ACTH stimulation and then fail to Tuberculosis (TB), an infection that can destroy secrete sufficient levels of cortisol. the adrenal glands, accounts for less than 20 per­ cent of cases of Addison’s disease in developed A person who stops taking a synthetic gluco­ countries.3 When adrenal insufficiency was first corticoid hormone may have enough ACTH to identified by Dr. Thomas Addison in 1849, TB function when healthy. However, when a person was the most common cause of the disease. As is under the stress of an illness, accident, or TB treatment improved, the incidence of adrenal surgery, the person’s body may not have enough insufficiency due to TB of the adrenal glands ACTH to stimulate the adrenal glands to pro­ greatly decreased. duce cortisol. Another cause of secondary adrenal insuffi­ 3MunverR, Volfson IA. Adrenal insufficiency: diagnosis ciency is surgical removal of the noncancerous, and management. Current Urology Reports. 2006;7:80–85. ACTH-producing tumors of the pituitary gland 3 Adrenal Insufficiency and Addison’s Disease
  4. 4. that cause Cushing’s disease. Cushing’s disease Both low- and high-dose ACTH stimulation tests is another disorder that leads to excess cortisol may be used depending on the suspected cause of in the body. In this case, the source of ACTH adrenal insufficiency. For example, if secondary is suddenly removed and replacement hormone adrenal insufficiency is mild or of recent onset, must be taken until normal ACTH and cortisol the adrenal glands may still respond to ACTH production resumes. because they have not yet atrophied. Some stud­ ies suggest a low dose—1 microgram—may be Less commonly, adrenal insufficiency occurs more effective in detecting secondary adrenal when the pituitary gland either decreases in size insufficiency because the low dose is still enough or stops producing ACTH. These events can to raise cortisol levels in healthy people but not result from in people with mild or recent secondary adrenal • tumors or infections of the area insufficiency. • loss of blood flow to the pituitary CRH Stimulation Test • radiation for the treatment of pituitary When the response to the ACTH test is abnor­ tumors mal, a CRH stimulation test can help determine • surgical removal of parts of the the cause of adrenal insufficiency. In this test, hypothalamus synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90, • surgical removal of the pituitary gland and 120 minutes after the injection. People with Addison’s disease respond by producing high lev­ How is adrenal insufficiency els of ACTH but no cortisol. People with second­ diagnosed? ary adrenal insufficiency have absent or delayed ACTH responses. CRH will not stimulate ACTH In its early stages, adrenal insufficiency can be secretion if the pituitary is damaged, so an absent difficult to diagnose. A review of a patient’s ACTH response points to the pituitary as the medical history and symptoms may lead a doctor cause. A delayed ACTH response points to the to suspect Addison’s disease. hypothalamus as the cause. A diagnosis of adrenal insufficiency is confirmed through laboratory tests. The aim of these tests Diagnosis during an Emergency is first to determine whether levels of cortisol In patients suspected of having an Addisonian are insufficient and then to establish the cause. crisis, health professionals must begin treatment Radiologic exams of the adrenal and pituitary with injections of salt, glucose-containing flu­ glands also are useful in helping to establish the ids, and glucocorticoid hormones immediately. cause. Although a reliable diagnosis is not possible during crisis treatment, measurement of blood ACTH Stimulation Test ACTH and cortisol during the crisis—before The ACTH stimulation test is the most com­ glucocorticoids are given—is enough to make a monly used test for diagnosing adrenal insuffi­ preliminary diagnosis. Low blood sodium, low ciency. In this test, blood cortisol, urine cortisol, blood glucose, and high blood potassium are also or both are measured before and after a synthetic usually present at the time of an adrenal crisis. form of ACTH is given by injection. The nor­ Once the crisis is controlled, an ACTH stimula­ mal response after an ACTH injection is a rise tion test can be performed to obtain the specific in blood and urine cortisol levels. People with diagnosis. More complex laboratory tests are Addison’s disease or long-standing secondary sometimes used if the diagnosis remains unclear. adrenal insufficiency have little or no increase in cortisol levels. 4 Adrenal Insufficiency and Addison’s Disease
  5. 5. Other Tests solution with dextrose, a type of sugar. This Once a diagnosis of Addison’s disease is made, treatment usually brings rapid improvement. radiologic studies such as an x ray or an ultra­ When the patient can take fluids and medica­ sound of the abdomen may be taken to see if tions by mouth, the amount of glucocorticoids is the adrenals have any signs of calcium deposits. decreased until a maintenance dose is reached. Calcium deposits may indicate bleeding in the If aldosterone is deficient, maintenance therapy adrenal gland or TB, for which a tuberculin skin also includes oral doses of fludrocortisone test also may be used. Blood tests can detect acetate. antibodies associated with autoimmune Addi­ son’s disease. What special problems If secondary adrenal insufficiency is diagnosed, can occur with adrenal doctors may use different imaging tools to reveal insufficiency? the size and shape of the pituitary gland. The most common is the computerized tomography Surgery (CT) scan, which produces a series of x-ray pic­ Because cortisol is a “stress hormone,” people tures giving cross-sectional images. A magnetic with chronic adrenal insufficiency who need any resonance imaging (MRI) scan may also be used type of surgery requiring general anesthesia must to produce a three-dimensional image of this be treated with intravenous glucocorticoids and region. The function of the pituitary and its abil­ saline. Intravenous treatment begins before ity to produce other hormones also are assessed surgery and continues until the patient is fully with blood tests. awake after surgery and able to take medication by mouth. The “stress” dosage is adjusted as How is adrenal insufficiency the patient recovers until the presurgery mainte­ nance dose is reached. treated? In addition, people who are not currently taking Treatment of adrenal insufficiency involves glucocorticoids but who have taken long-term replacing, or substituting, the hormones that glucocorticoids in the past year should tell their the adrenal glands are not making. Cortisol is doctor before surgery. These people may have replaced with a synthetic glucocorticoid such sufficient ACTH for normal events, but they as hydrocortisone, prednisone, or dexametha­ may need intravenous treatment for the stress of sone, taken orally once to three times each day, surgery. depending on which medication is chosen. If aldosterone is also deficient, it is replaced with Illness oral doses of a mineralocorticoid, called fludro­ cortisone acetate (Florinef), taken once or twice During illness, oral dosing of glucocorticoid a day. Doctors usually advise patients receiving may be adjusted to mimic the normal response aldosterone replacement therapy to increase of the adrenal glands to this stress on the body. their salt intake. Because people with secondary Significant fever or injury may require triple oral adrenal insufficiency normally maintain aldos­ dosing. Once recovery from the stress event is terone production, they do not require aldos­ achieved, dosing is then returned to maintenance terone replacement therapy. The doses of each levels. People with adrenal insufficiency should medication are adjusted to meet the needs of the know how to increase medication during such individual. periods of stress. Immediate medical attention is needed if severe infections, vomiting, or diar­ During an Addisonian crisis, low blood pressure, rhea occur. These conditions can precipitate an low blood glucose, and high levels of potas­ Addisonian crisis. sium can be life threatening. Standard therapy involves intravenous injections of glucocorti­ coids and large volumes of intravenous saline 5 Adrenal Insufficiency and Addison’s Disease
  6. 6. Pregnancy Women with adrenal insufficiency who become pregnant are treated with standard replacement Points to Remember therapy. If nausea and vomiting in early preg­ • Adrenal insufficiency is a disorder that nancy interfere with taking medication by mouth, occurs when the adrenal glands do not injections of the hormone may be necessary. produce enough of certain hormones. During delivery, treatment is similar to that of • Primary adrenal insufficiency, also people needing surgery. Following delivery, the called Addison’s disease, occurs when dose is gradually tapered and the usual mainte­ the adrenal glands are damaged and nance doses of oral hydrocortisone and fludro­ cannot produce enough of the hor­ cortisone acetate are reached about 10 days after mone cortisol and often the hormone childbirth. aldosterone. • Secondary adrenal insufficiency occurs How can someone with when the pituitary gland fails to adrenal insufficiency produce enough adrenocorticotropin prepare for an emergency? (ACTH), a hormone that stimulates the adrenals to produce cortisol. If People with adrenal insufficiency should always ACTH output is too low, cortisol pro­ carry identification stating their condition in case duction drops. of an emergency. A card or medical alert tag should notify emergency health care providers of • The most common symptoms of adre­ the need to inject cortisol if the person is found nal insufficiency are chronic, worsen­ severely injured or unable to answer questions. ing fatigue; muscle weakness; loss of The card or tag should also include the name and appetite; and weight loss. telephone number of the person’s doctor and the • Adrenal insufficiency is most often name and telephone number of a family mem­ diagnosed through blood or urine ber to be notified. The dose of hydrocortisone tests. Imaging studies such as x rays, needed may vary with a person’s age or size. For ultrasound, computerized tomography example, a child younger than 2 years of age can (CT), and magnetic resonance imaging receive 25 milligrams (mg), a child between 2 and (MRI) may also be used. 8 years of age can receive 50 mg, and a child older than 8 years should receive the adult dose • Treatment of adrenal insufficiency of 100 mg. When traveling, people with adrenal involves replacing, or substituting, the insufficiency should carry a needle, syringe, and hormones that the adrenal glands are an injectable form of cortisol for emergencies. not making. • People with adrenal insufficiency should always carry identification stating their condition in case of an emergency. 6 Adrenal Insufficiency and Addison’s Disease
  7. 7. Hope through Research The following organizations might also be able to assist with certain types of information: Researchers are evaluating the use of another adrenal hormone, dehydroepiandrosterone, in American Autoimmune Related Diseases improving the health-related quality of life in Association people with adrenal insufficiency. Scientists are National Office also studying the occurrence of “relative” adrenal 22100 Gratiot Avenue insufficiency—below normal production of adre­ East Detroit, MI 48021 nal hormones during critical illness—to further Phone: 586–776–3900 define this type of adrenal insufficiency, develop Email: diagnostic tests, and identify the best treatment Internet: options. National Adrenal Diseases Foundation Participants in clinical trials can play a more 505 Northern Boulevard, Suite 200 active role in their own health care, gain access Great Neck, NY 11021 to new research treatments before they are Phone: 516–487–4992 widely available, and help others by contributing Email: to medical research. For information about cur­ Internet: rent studies, visit Acknowledgments For More Information Publications produced by the NIDDK are care­ The following articles about Addison’s disease fully reviewed by both NIDDK scientists and can be found in medical libraries, some college outside experts. This publication was reviewed and university libraries, and through interlibrary by Karen Loechner, M.D., Ph.D., University of loan in most public libraries. North Carolina at Chapel Hill. Chrousos GP. Glucocorticoid therapy. In: Felig P, Frohman L, eds. Endocrinology and You may also find additional information about this Metabolism. 4th ed. New York: McGraw-Hill; topic by 2001:609–632. • searching the NIDDK Reference Collection at Munver R, Volfson IA. Adrenal insufficiency: diagnosis and management. Current Urology • visiting MedlinePlus at Reports. 2006;7:80–85. This publication may contain information about med­ Nieman LK, Chanco Turner ML. ications. When prepared, this publication included the most current information available. For updates Addison’s disease. Clinics in Dermatology. or for questions about any medications, contact 2006;24(4):276–280. the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–888–463–6332) or visit Stewart PM. The adrenal cortex. In: Larsen P, Consult your doctor for more ed. Williams Textbook of Endocrinology. 10th ed. information. Philadelphia: Saunders; 2003:491–551. Ten S, New M, Maclaren N. Clinical Review 130: Addison’s disease 2001. Journal The U.S. Government does not endorse or favor any of Clinical Endocrinology & Metabolism. specific commercial product or company. Trade, 2001;86(7):2909–2922. proprietary, or company names appearing in this document are used only because they are considered Williams GH, Dluhy RC. Disorders of necessary in the context of the information provided. the adrenal cortex. In: Braunwald E, ed. If a product is not mentioned, the omission does not Harrison’s Principles of Internal Medicine. mean or imply that the product is unsatisfactory. 17th ed. New York: McGraw-Hill Professional; 2008:2247–2268. 7 Adrenal Insufficiency and Addison’s Disease
  8. 8. National Endocrine and Metabolic Diseases Information Service 6 Information Way Bethesda, MD 20892–3569 Phone: 1–888–828–0904 TTY: 1–866–569–1162 Fax: 703–738–4929 Email: Internet: The National Endocrine and Metabolic Diseases Information Service is an information dissemination service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health, which is part of the U.S. Department of Health and Human Services. The NIDDK conducts and supports biomedical research. As a public service, the NIDDK has established information services to increase knowledge and understanding about health and disease among patients, health care professionals, and the public. This publication is not copyrighted. The NIDDK encourages users of this fact sheet to duplicate and distribute as many copies as desired. This fact sheet is also available at U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIH Publication No. 09–3054 May 2009