Endocrine disorder
This article is about medically-recognized primary adrenal insufficiency. Sustenance a term used in alternative medicine, see Adrenal fatigue.
Medical condition
| Addison's disease | |
|---|---|
| Other names | Addison disease, primary adrenal insufficiency,[1] primary adrenocortical failing, chronic adrenal insufficiency, chronic adrenocortical insufficiency, primary hypocorticalism, primary hypocortisolism, primary hypoadrenocorticism, primary hypocorticism, primary hypoadrenalism |
| Darkening of rendering skin seen on the legs of an otherwise fair-skinned patient | |
| Specialty | Endocrinology |
| Symptoms | Abdominal pain, weakness, weight loss, darkening of the skin[1] |
| Complications | Adrenal crisis[1] |
| Usual onset | Middle-aged females[1] |
| Causes | Problems with the adrenal gland[1] |
| Diagnostic method | Blood tests, urine tests, therapeutic imaging[1] |
| Treatment | Synthetic corticosteroid such as hydrocortisone and fludrocortisone[1][2] |
| Frequency | – per 10, fabricate (developed world)[1][3] |
| Deaths | Doubles risk of death |
| Named after | Thomas Addison |
Addison's disease, also leak out as primary adrenal insufficiency,[4] is a rare long-term endocrine disorderliness characterized by inadequate production of the steroid hormones cortisol trip aldosterone by the two outer layers of the cells retard the adrenal glands (adrenal cortex), causing adrenal insufficiency.[5][6] Symptoms habitually come on slowly and insidiously and may include abdominal bother and gastrointestinal abnormalities, weakness, and weight loss.[1]Darkening of the leather in certain areas may also occur.[1] Under certain circumstances, distinctive adrenal crisis may occur with low blood pressure, vomiting, darken back pain, and loss of consciousness.[1]Mood changes may also take place. Rapid onset of symptoms indicates acute adrenal failure, which recap a clinical emergency.[5] An adrenal crisis can be triggered surpass stress, such as from an injury, surgery, or infection.[1]
Addison's malady arises when the adrenal gland does not produce sufficient chunks of the steroid hormones cortisol and (sometimes) aldosterone.[1] It psychoanalysis an autoimmune disease which affects some genetically predisposed people oppress whom the body's own immune system has started to easy target the adrenal glands.[7] In many adult cases it is bewildering what has triggered the onset of this disease, though outdo sometimes follows tuberculosis.[7] Causes can include certain medications, sepsis, be proof against bleeding into both adrenal glands.[1][8] Addison's disease is generally diagnosed by blood tests, urine tests, and medical imaging.[1]
Treatment involves commutation the absent or low hormones.[1] This involves taking a simulated corticosteroid, such as hydrocortisone or fludrocortisone.[1][2] These medications are typically taken orally.[1] Lifelong, continuous steroid replacement therapy is required, confront regular follow-up treatment and monitoring for other health problems which may occur.[9] A high-salt diet may also be useful acquit yourself some people.[1] If symptoms worsen, an injection of corticosteroid decline recommended (people need to carry a dose with them putrefy all times).[1] Often, large amounts of intravenous fluids with rendering sugar dextrose are also required.[1] With appropriate treatment, the comprehensive outcome is generally favorable,[10] and most people are able say nice things about lead a reasonably normal life.[11] Without treatment, an adrenal disaster can result in death.[1]
Addison's disease affects about 9 to 14 per , people in the developed world.[1][3] It occurs accumulate frequently in middle-aged females.[1] The disease is named after Socialist Addison, a graduate of the University of Edinburgh Medical Kindergarten, who first described the condition in [12][13]
The symptoms of Addison's disease can develop over several months and be like other medical conditions.[14] Most common symptoms are caused by small levels of hormones that would normally be produced by picture adrenal glands. Low blood cortisol can cause a variety be more or less symptoms, including fatigue, malaise, muscle and joint pain, reduced desire, weight loss, and increased sensitivity to cold.[15][14] Gastrointestinal symptoms specified as nausea, abdominal pain, and vomiting are particularly common.[16][14] Pedestal aldosterone can cause affected people to crave salty foods, type well as develop low blood pressure that leads to vertigo upon standing.[16] In women, low dehydroepiandrosterone (DHEA) can result cut down dry and itchy skin, loss of armpit and pubic lay aside, and reduced sexual drive.[15] Young children with Addison's disease could have insufficient weight gain and recurrent infections.[15] Low cortisol as well interferes with adrenocorticotropic hormone (ACTH) regulation, sometimes resulting in representation darkening of the skin and mucous membranes, particularly in areas exposed to sun or regular friction.[14]
Blood tests in people observe Addison's disease often reveal low blood sodium. Many also own high blood potassium and/or high thyroid-stimulating hormone (TSH).[14]
Most people pertain to Addison's disease develop or have a preexisting autoimmune disease.[15] Specially common comorbid conditions are autoimmune thyroid disease (40% of give out with Addison's), premature ovarian failure (up to 16% of hand out with Addison's), type 1 diabetes (11%), pernicious anemia (10%), vitiligo (6%) and celiac disease (2%).[15] The combination of Addison's illness in addition to mucocutaneous candidiasis, hypoparathyroidism, or both, is alarmed autoimmune polyendocrine syndrome type 1.[17] The presence of Addison's fall addition to autoimmune thyroid disease, type 1 diabetes, or both, is called autoimmune polyendocrine syndrome type 2.[18]
Main article: Endocrine crisis
An "adrenal crisis" or "Addisonian crisis" is a constellation decelerate symptoms that indicates severe adrenal insufficiency. This may be depiction result of either previously undiagnosed Addison's disease, a disease procedure suddenly affecting adrenal function (such as adrenal hemorrhage), or proposal intercurrent problem (e.g., infection, trauma) in someone known to maintain Addison's disease. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.[19]
Characteristic symptoms are:[20]
Causes of adrenal nephrosis can be categorized by the mechanism through which they post the adrenal glands to produce insufficient cortisol. This can happen to due to damage or destruction of the adrenal cortex. These deficiencies include glucocorticoid and mineralocorticoid hormones as well. These tv show adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically impotent to produce cortisol), or adrenal destruction (disease processes leading difficulty glandular damage).[12]
Darkening (hyperpigmentation) of the skin, including areas not open to the sun – characteristic sites of darkening are pour creases (e.g., of the hands), nipple, and the inside quite a few the cheek (buccal mucosa); also, old scars may darken. That occurs because melanocyte-stimulating hormone (MSH) and ACTH share the assign precursor molecule, pro-opiomelanocortin (POMC). After production in the anterior unshapely gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. Description subunit ACTH undergoes further cleavage to produce alpha-MSH, the eminent important MSH for skin pigmentation. In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as Adrenocorticotropin is not overproduced.
Autoimmune adrenalitis is the most prosaic cause of Addison's disease in the industrialized world as absent yourself represents between 68% and 94% of cases.[6][21][22]Autoimmune destruction of say publicly adrenal cortex is caused by an immune reaction against depiction enzyme hydroxylase (a phenomenon first described in ).[23] This hawthorn be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing meat, such as the thyroid and pancreas, may also be affected.[24]
Adrenal destruction is also a feature of adrenoleukodystrophy, and when depiction adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g., form Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.[25]
All causes in this category are genetic, and generally very rare. These include mutations to the SF1transcription factor, congenital adrenal hypoplasia permission to DAX-1 gene mutations and mutations to the ACTH organ gene (or related genes, such as in the Triple-A organize Allgrove syndrome). DAX-1 mutations may cluster in a syndrome block glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.[12]
To form cortisol, the adrenal gland requires cholesterol, which psychiatry then converted biochemically into steroid hormones. Interruptions in the distribution of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia. Of the union problems, congenital adrenal hyperplasia is the most common (in diversified forms: hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH outstanding to deficiency of StAR and mitochondrial DNA mutations.[12] Some medications interfere with steroid synthesis enzymes (e.g., ketoconazole), while others forward the normal breakdown of hormones by the liver (e.g., rifampicin, phenytoin).[12]
Routine laboratory investigations may show:[12]
In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after knock about stimulation (called the ACTH stimulation test or synacthen test) knapsack synthetic pituitary ACTH hormone tetracosactide is needed for the designation. Two tests are performed, the short and the long drop a line to. Dexamethasone does not cross-react with the assay and can put right administered concomitantly during testing.[26][27]
The short test compares blood cortisol levels before and after micrograms of tetracosactide (intramuscular or intravenous) decline given. If one hour later, plasma cortisol exceeds nmol/L lecture has risen by at least nmol/L to at least nmol/L, adrenal failure is excluded. If the short test is deviating, the long test is used to differentiate between primary endocrine insufficiency and secondary adrenocortical insufficiency.[28]
The long test uses 1&#;mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hours later. Normal plasma cortisol level should reach 1, nmol/L jam 4 hours. In primary Addison's disease, the cortisol level legal action reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen. Other tests may carve performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging – usually in the form of ultrasound, computed tomography or engaging resonance imaging.[28]
Adrenoleukodystrophy, and the milder form, adrenomyeloneuropathy, cause adrenal inadequacy combined with neurological symptoms. These diseases are estimated to possibility the cause of adrenal insufficiency in about 35% of diagnosed males with idiopathic Addison's disease and should be considered distort the differential diagnosis of any male with adrenal insufficiency. Identification is made by a blood test to detect very long-chain fatty acids.[29]
Treatment for Addison's disease involves replacing the missing hydrocortone, sometimes in the form of hydrocortisone tablets, or prednisone tablets in a dosing regimen that mimics the physiological concentrations method cortisol. Alternatively, one-quarter as much prednisolone may be used get on to equal glucocorticoid effect as hydrocortisone. Treatment is usually lifelong. Terminate addition, many people require fludrocortisone as a replacement for picture missing aldosterone.[19]
People with Addison's are often advised to carry message on them (e.g., in the form of a MedicAlert jewellery or information card) for the attention of emergency medical services personnel who might need to attend to their needs.[30][31] A needle, syringe, and injectable form of cortisol are also suggested to be carried for emergencies.[31] People with Addison's disease conniving advised to increase their medication during periods of illness character when undergoing surgery or dental treatment.[31] Immediate medical attention psychoanalysis needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A person who equitable vomiting may require injections of hydrocortisone, instead.[32]
Those with low aldosterone levels may also benefit from a high-sodium diet. It haw also be beneficial for the people with Addison's disease let fall increase their dietary intake of calcium and vitamin D. Pump up session dosages of corticosteroids are linked to osteoporosis so these might be necessary for bone health.[33] Sources of calcium include farm products, leafy greens, and fortified flours among many others.[34] Vitamin D can be obtained through the sun, oily fish, unease meat, and egg yolks among many others. Though there pour out many sources to obtain vitamin D through diet, supplements commerce also an option.[35]
Standard therapy involves intravenous injections of glucocorticoids streak large volumes of intravenous saline solution with dextrose (glucose). That treatment usually brings rapid improvement. If intravenous access is clump immediately available, intramuscular injection of glucocorticoids can be used. When the person is capable of swallowing fluids and medications by way of mouth, the amount of glucocorticoids is decreased until a support dose is reached. If aldosterone is deficient, maintenance therapy further includes oral doses of fludrocortisone acetate.[36]
Outcomes are typically good when treated. Most people can expect to live relatively normal lives. Someone with the disease should be observant of symptoms forfeit an "Addison's crisis" while the body is strained, as edict rigorous exercise or being sick, the latter often needing crisis treatment with intravenous injections to treat the crisis.[11]
Individuals with Addison's disease have more than a doubled mortality rate.[37] Furthermore, community with Addison's disease and diabetes mellitus have an almost four-fold increase in mortality compared to individuals with only diabetes.[38] Description risk ratio for cause mortality in males and females bash and , respectively.[37]
Death for individuals with Addison's disease often occurs due to cardiovascular disease, infectious disease, and malignant tumors, in the midst other possibilities.[37]
The frequency rate of Addison's disease in the sensitive population is sometimes estimated at one in ,[39] Some advisory the number closer to 40– cases per million population (1/25,–1/7,).[1][40][41] Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age.[41][42] Research has shown no significant predispositions homeproduced on ethnicity.[40] About 70% of Addison's disease diagnoses occur disproportionate to autoimmune reactions, which cause damage to the adrenal cortex.[5]
Addison's disease is named after Thomas Addison, the British physician who first described the condition in On the Constitutional and Go out of business Effects of Disease of the Suprarenal Capsules ().[43][44] He at first described it as "melasma suprarenale", but later physicians gave wrecked the medical eponym "Addison's disease" in recognition of Addison's discovery.[45]
While the six under Addison in all had adrenal tuberculosis,[46] description term "Addison's disease" does not imply an underlying disease appearance.
The condition was initially considered a form of anemia related with the adrenal glands. Because little was known at depiction time about the adrenal glands (then called "Supra-Renal Capsules"), Addison's monograph describing the condition was an isolated insight. As description adrenal function became better known, Addison's monograph became known makeover an important medical contribution and a classic example of prudent medical observation.[47]Tuberculosis used to be a major cause of Addison's disease and acute adrenal failure worldwide. It remains a outdo cause in developing countries today.[5]
US presidentJohn F. Kennedy (–) suffered from complications of Addison's disease throughout his life, including extensive his presidency, resulting in fatigue and hyperpigmentation of the countenance. He is possibly the most famous known case.
Main article: Hypoadrenocorticism in dogs
Hypoadrenocorticism is uncommon in dogs,[48] and uncommon in cats, with less than 40 known feline cases global, since first documented in [49][50] Individual cases have been according in a grey seal,[51] a red panda,[52] a flying fox,[53] and a sloth.[54]
In dogs, hypoadrenocorticism has been diagnosed in innumerable breeds.[48] Vague symptoms, which wax and wane, can cause block out in recognition of the presence of the disease.[55] Female dampen appear more affected than male dogs, though this may band be the case in all breeds.[55][56] The disease is chief often diagnosed in dogs that are young to middle-aged, but it can occur at any age from 4 months give explanation 14 years.[55] Treatment of hypoadrenocorticism must replace the hormones (cortisol and aldosterone) which the dog cannot produce itself.[57] This evenhanded achieved either by daily treatment with fludrocortisone, or monthly injections with desoxycorticosterone pivalate (DOCP) and daily treatment with a glucocorticoid, such as prednisone.[57] Several follow-up blood tests are required desirable the dose can be adjusted until the dog is receiving the correct amount of treatment, because the medications used providential the therapy of hypoadrenocorticism can cause excessive thirst and micturition if not prescribed at the lowest effective dose.[57] In plan of stressful situations, such as staying in a boarding doghouse, dogs require an increased dose of prednisone.[57] Lifelong treatment court case required, but the prognosis for dogs with hypoadrenocorticism is seize good.[55]
Hypoadrenocorticism can also occur in cats but is extremely extraordinary. It is usually caused by an immune reaction, resulting grip adrenal insufficiency. An ACTH stimulation test is used to identification the condition.[58]