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| | __NOTOC__ |
| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = Addison's disease | | | Name = {{PAGENAME}} | |
| Image = | | | Image = Addisons hyperpigmentation.jpg| |
| Caption = | | | Caption = Classic hyperpigmentation of Addison's disease; |
| DiseasesDB = 222 | | | Source:By FlatOut - Dermatology Online Journal http://dermatology.cdlib.org/, CC0, https://commons.wikimedia.org/w/index.php?curid=25847348| |
| ICD10 = {{ICD10|E|27|1|e|20}}-{{ICD10|E|27|2|e|20}} | | | DiseasesDB = 76715008 | |
| ICD9 = {{ICD9|255.4}} | | | ICD10 = {{ICD10|E|27.1}}| |
| | ICD9 = {{ICD9|255.41}} | |
| ICDO = | | | ICDO = | |
| OMIM = | | | OMIM = | |
| MedlinePlus = 000378| | | MedlinePlus = | |
| eMedicineSubj = med | | | eMedicineSubj = | |
| eMedicineTopic = 42 | | | eMedicineTopic = | |
| MeshID = D000224 |
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| }} | | }} |
| {{SI}} | | {{Addison's disease}} |
| __NOTOC__
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| {{GS}}
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| {{Editor Join}}
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| ==Overview==
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| '''Addison's disease''' (also known as '''chronic [[adrenal insufficiency]]''', [[cortisol|'''hypocortisolism''' or '''hypocorticism]]''') is a rare [[endocrine]] disorder in which the [[adrenal gland]] produces insufficient amounts of [[steroid hormone]]s ([[glucocorticoid]]s and often [[mineralocorticoid]]s). It may develop in children as well as adults, and may occur as the result of a large number of underlying causes. <ref>[http://www.niddk.nih.gov/health/endo/pubs/addison/addison.htm NIH Publication No. 04–3054: Addison's disease. A work by Endocrine and Metabolic Diseases Information Service. National Institute for Health. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 2004 June]</ref>
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| The condition is named after Dr [[Thomas Addison]], the British [[physician]] who first described the condition in his 1855 ''On the Constitutional and Local Effects of Disease of the Suprarenal Capsules''.<ref>{{cite book | author = Thomas Addison | authorlink = Thomas Addison | title = On The Constitutional And Local Effects Of Disease Of The Supra-Renal Capsules | origyear = 1855 | url = http://www.wehner.org/addison/x1.htm | format = HTML reprint | publisher = Samuel Highley | location = London}}</ref> The adjective "Addisonian" is used for features of the condition, as well as patients with Addison's disease.<ref name=Ten>{{cite journal |author=Ten S, New M, Maclaren N |title=Clinical review 130: Addison's disease 2001 |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=7 |pages=2909-22 |year=2001 |pmid=11443143 |url=http://jcem.endojournals.org/cgi/content/full/86/7/2909}}</ref>
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| The condition is generally diagnosed with [[blood test]]s, [[medical imaging]] and additional investigations.<ref name=Ten/> Treatment is with replacement of the hormones (oral [[hydrocortisone]] and [[fludrocortisone]]). If the disease is caused by an underlying problem, this is addressed. Regular follow-up and monitoring for other health problems is necessary.<ref name=Ten/>
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| == Epidemiology ==
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| The frequency rate of Addison's disease in the human population is sometimes estimated at roughly 1 in 100,000.<ref>{{cite web |url=http://www.medicinenet.com/addison_disease/article.htm |title=Addison Disease � Health information regarding this hormonal (endocrine) disorder on MedicineNet.com |format= |work=}}</ref> Some research and information sites put the number closer to 40-60 cases per 1 million population. (1/25,000-1/16,600)<ref name="emedicinemed42">{{cite web |url=http://www.emedicine.com/med/topic42.htm |title=eMedicine - Addison Disease : Article by Sylvester Odeke|format= |work=}}</ref>
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| (Determining accurate numbers for Addison's is problematic at best and some incidence figures are thought to be underestimates.<ref>{{cite web |url=http://www.medhelp.org/www/nadf3.htm |title=medhelp |format= |work=}}</ref>)
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| Addison's can afflict persons of any age, gender, or ethnicity, but typically presents in adults between 30 and 50 years of age. Women are slightly more likely to develop Addison's according to some studies. Research has shown no significant predispositions based on ethnicity.<ref name="emedicinemed42"> </ref>
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| == Etiology and Pathophysiology of Addison's Disease==
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| Causes of adrenal insufficiency can be grouped by the way in which they cause the adrenals to produce insufficient cortisol. These are ''adrenal dysgenesis'' (the gland has not formed adequately during development), ''impaired steroidogenesis'' (the gland is present but is biochemically unable to produce cortisol) or ''adrenal destruction'' (disease processes leading to the gland being damaged).<ref name=Ten/>
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| ===Adrenal dysgenesis===
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| All causes in this category are genetic, and generally very rare. These include [[genetic mutation|mutations]] to the ''SF1'' [[transcription factor]], [[X-linked adrenal hypoplasia congenita|congenital adrenal hypoplasia]] (AHC) due to ''DAX-1'' gene mutations and mutations to the [[ACTH receptor]] gene (or related genes, such as in the [[Triple A syndrome|Triple A]] or Allgrove syndrome). ''DAX-1'' mutations may cluster in a syndrome with [[glycerol kinase]] deficiency with a number of other symptoms when ''DAX-1'' is deleted together with a number of other genes.<ref name=Ten/>
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| ===Impaired steroidogenesis===
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| To form cortisol, the adrenal gland requires [[cholesterol]], which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include [[Smith-Lemli-Opitz syndrome]] and [[abetalipoproteinemia]]. Of the synthesis problems, [[congenital adrenal hyperplasia]] is the most common (in various forms: [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency|21-hydroxylase]], [[Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency|17α-hydroxylase]], [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency|11β-hydroxylase]] and [[Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency|3β-hydroxysteroid dehydrogenase]]), [[Lipoid congenital adrenal hyperplasia|lipod CAH]] due to deficiency of [[steroidogenic acute regulatory protein|StAR]] and [[mitochondrial DNA]] mutations.<ref name=Ten/>
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| ===Adrenal destruction===
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| [[Autoimmunity|Autoimmune]] destruction of the adrenal cortex (often due to antibodies against the enzyme [[21-Hydroxylase]]) is a common cause of Addison's in teenagers and adults. This may be isolated or in the context of [[autoimmune polyendocrine syndrome]] (APS type 1 or 2). Adrenal destruction is also a feature of [[adrenoleukodystrophy]] (ALD), and when the adrenal glands are involved in [[metastasis]] (seeding of [[cancer]] cells from elsewhere in the body), [[hemorrhage]] (e.g. in [[Waterhouse-Friderichsen syndrome]] or [[antiphospholipid syndrome]]), particular [[infection]]s ([[tuberculosis]], [[histoplasmosis]], [[coccidioidomycosis]]), deposition of abnormal protein in [[amyloidosis]]. Some medications interfere with steroid synthesis enzymes (e.g. [[ketoconazole]]), while others accelerate the normal breakdown of hormones by the [[liver]] (e.g. [[rifampicin]], [[phenytoin]]).<ref name=Ten/>
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| == Complete differential diagnosis of causes of Addison's disease classified by Primary and Secondary causes <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:14-15</ref> ==
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| === Primary Adrenocoritcal Insufficiency (Addison's disease) ===
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| * Autoimmune/idiopathic
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| * Congenital
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| *:* [[Congenital adrenal hyperplasia]]
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| *:* [[Glucocorticoid deficiency 1]]
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| *:* [[Adrenal aplasia]] / hypoplasia
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| * Iatrogenic
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| *:* [[Radiation]] (therapy)
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| *:* Bilateral [[adrenalectomy]]
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| * Fungal
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| *:* [[Cryptococcosis]]
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| *:*:* [[Histoplasmosis]]
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| *:* [[Blastomycosis]]
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| *:* [[Syphilis]]
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| *:* [[Coccidiomycosis]]
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| *:* [[Tuberculosis]] (20% of all Addison's)
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| * Hemorrhage, infarction
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| *:* [[Trauma]]
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| *:* Surgery
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| *:* [[Sepsis]]
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| *:*:* [[Waterhouse-Friderichson syndrome]]
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| *:* [[Embolus]]
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| *:* Anticoagulation
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| *:* [[Arteritis]]
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| *:* [[Hypotension]]
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| *:* Neonatal
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| *:* Thrombosis
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| *:* [[Coagulopathy]]
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| * Infections
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| *:* [[AIDS]]
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| *:*:* [[Toxoplasmosis]]
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| *:*:* [[Kaposi's sarcoma]]
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| *:*:* [[CMV]]
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| *:*:* [[Mycobacterium avium intracellulaire]] ([[MAI]])
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| *:*:* [[Cryptococcosis]]
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| * Neoplasm
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| *:* [[Adrenal metastases]]
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| *:* [[Leukemia]]
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| *:* [[Lymphoma]]
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| * [[Uremia]]
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| * [[Coma]]
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| * Infiltrative
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| *:* [[Amyloidosis]]
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| *:* [[Sarcoidosis]]
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| *:* [[Hemochromatosis]]
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| * Volume / electrolyte disorders
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| * [[Drugs]]
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| === Secondary (pituitary) or Tertiary (hypothalamic) Adrenocortical Insufficiency ===
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| * Drug withdrawal
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| * After surgery of [[cortisol]]-secreting tumor
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| ==Signs and symptoms==
| | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| ===Symptoms===
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| The symptoms of Addison's disease develop insidiously, and it may take some time to be recognized. The most common symptoms are [[fatigue (medical)|fatigue]], [[muscle weakness]], weight loss, [[vomiting]], [[diarrhea]], [[headache]], [[sweating]], changes in mood and personality and [[arthralgia|joint]] and [[myalgia|muscle pains]]. Some have marked cravings for salty foods due to the urinary losses of sodium.<ref name=Ten/>
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| === Clinical signs===
| | {{CMG}}; {{AE}} {{ADG}} |
| On examination, the following may be noticed:<ref name=Ten/>
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| * [[Hypotension|Low blood pressure]] that falls further when standing ([[orthostatic hypotension]])
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| * Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipples, and the inside of the cheek (buccal mucosa), also old scars may darken.
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| * Signs of conditions that often occur together with Addison's: [[goiter]] and [[vitiligo]]
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| === Addisonian crisis ===
| | {{SK}} Autoimmune adrenalitis; Addison disease; primary adrenal insufficiency; chronic adrenocortical insufficiency; Addisonian crisis, acquired primary adrenal insufficiency, adrenocortical insufficiency, chronic adrenal insufficiency, corticoadrenal insufficiency, hypocortisolism, primary adrenal insufficiency, primary adrenocortical insufficiency |
| An "Addisonian crisis" or "adrenal crisis" is a constellation of symptoms that indicate severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as [[adrenal hemorrhage]]), or an intercurrent problem (e.g. infection, trauma) in the setting of known Addison's disease. Additionally, this situation may develop in those on long-term oral [[glucocorticoid]]s who have suddenly ceased taking their medication. It is also a concern in the setting of [[myxedema coma]]; [[thyroxine]] given in that setting without [[glucocorticoid]]s may precipitate a crisis.
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| Untreated, an Addisonian crisis can be fatal. It is a [[medical emergency]], usually requiring hospitalization. Characteristic symptoms are:<ref>[http://www.endocrine.niddk.nih.gov/pubs/addison/addison.htm#symptoms Addison's Disease] National Endocrine and Metabolic Diseases Information Service. Retrieved on 26 October, 2007.</ref>
| | ==[[Addison's disease overview|Overview]]== |
| * Sudden penetrating pain in the legs, lower back or abdomen
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| * Severe vomiting and diarrhea, resulting in [[dehydration]]
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| * [[Hypotension|Low blood pressure]]
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| * [[Fainting|Loss of consciousness/Syncope]]
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| * [[Hypoglycemia]]
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| * [[Confusion]], [[psychosis]]
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| * [[Seizure|Convulsions]]
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| == Diagnosis == | | ==[[Addison's disease historical perspective|Historical Perspective]]== |
| === Suggestive features===
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| Routine investigations may show:<ref name=Ten/>
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| * [[Hypoglycemia]], low blood sugar (worse in children)
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| * [[Hyponatraemia]] (low blood sodium levels)
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| * [[Hyperkalemia]] (raised blood [[potassium]] levels), due to loss of production of the hormone [[aldosterone]]
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| * [[Eosinophilia]] and [[lymphocytosis]] (increased number of [[eosinophil]]s or [[lymphocyte]]s, two types of [[white blood cell]]s)
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| ===Testing=== | | ==[[Addison's disease pathophysiology|Pathophysiology]]== |
| [[Image:Cortisol-2D-skeletal.png|thumb|[[Cortisol]]]][[Image:Aldosterone-2D-skeletal.png|thumb|[[Aldosterone]]]]
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| In suspected cases of Addison's disease, one needs to demonstrate that adrenal hormone levels are low even after appropriate stimulation with synthetic pituitary hormone [[tetracosactide]]. Two tests are performed, the short and the long test.
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| The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (IM/IV) is given.
| | ==[[Addison's disease causes|Causes]]== |
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| If, one hour later, [[plasma]] cortisol exceeds 170 nmol/L and has risen by at least 330 nmol/L to at least 690 nmol/L, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal failure and secondary adrenocortical failure.
| | ==[[Addison's disease differential diagnosis|Differentiating Addison's disease from other Diseases]]== |
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| The long test uses 1 mg tetracosactide (IM). Blood is taken 1, 4, 8, and 24 hours later.
| | ==[[Addison's disease epidemiology and demographics|Epidemiology and Demographics]]== |
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| Normal plasma cortisol level should reach 1000 nmol/L by 4 hours. In primary Addison's disease, the cortisol level is reduced at all stages whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.
| | ==[[Addison's disease risk factors|Risk Factors]]== |
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| Other tests that may be performed to distinguish between various causes of hypoadrenalism are [[renin]] and [[adrenocorticotropic hormone]] levels, as well as [[medical imaging]] - usually in the form of [[medical ultrasonography|ultrasound]], [[computed tomography]] or [[magnetic resonance imaging]] (MRI).
| | ==[[Addison's disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| == Treatment == | | ==Diagnosis== |
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| === Maintenance treatment===
| | [[Addison's disease history and symptoms|History and Symptoms]] | [[ Addison's disease physical examination|Physical Examination]] | [[Addison's disease laboratory findings|Laboratory Findings]] | [[Addison's disease electrocardiogram|Electrocardiogram]] | [[Addison's disease chest x ray|Chest X Ray]] | [[Addison's disease CT|CT]] | [[Addison's disease MRI|MRI]] | [[Addison's disease ultrasound|Ultrasound]] | [[Addison's disease other diagnostic studies|Other Diagnostic Studies]] |
| Treatment for Addison's disease involves replacing the missing cortisol (usually in the form of [[hydrocortisone]] tablets) in a dosing regimen that mimics the physiological concentrations of cortisol. Treatment must usually be continued for life. In addition, many patients require [[fludrocortisone]] as replacement for the missing aldosterone. Caution must be exercised when the person with Addison's disease becomes unwell, has [[surgery]] or becomes [[pregnant]]. Medication may need to be increased during times of stress, infection, or injury.
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| ===Addisonian crisis=== | | ==Treatment== |
| | [[Addison's disease medical therapy|Medical Therapy]] | [[Addison's disease surgery |Surgery]] | [[Addison's disease secondary prevention|Secondary Prevention]] | [[Addison's disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Addison's disease future or investigational therapies|Future or Investigational Therapies]] |
| | ==Case Studies== |
| | [[Addison's disease case study one|Case #1]] |
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| Treatment for an acute attack, an Addisonian crisis, usually involves intravenous (into blood veins) injections of:
| | ==Related Chapter== |
| * Cortisone ([[cortisol]])
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| * Saline solution (basically a salt water, same clear [[Intravenous therapy#Infusion equipment|IV bag]] as used to treat dehydration)
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| * [[Glucose]]
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| === Surgery === | |
| Surgeries may require significant adjustments to medication regimens prior to, during, and following any surgical procedure. The best preparation for any surgery, regardless of how minor or routine it may normally be, is to speak to one's primary physician about the procedure and medication implications well in advance of the surgery.
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| === Pregnancy ===
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| Many women with Addison's have given birth successfully and without complication, both through natural labor and through cesarean delivery. Both of these methods will require different preventative measures relating to Addison's medications and dosages. As is always the case, thorough communication with one's primary physician is the best course of action. Occasionally, oral intake of medications will cause debilitating nausea and vomiting, and thus the woman may be switched to injected medications until delivery. <ref>{{cite web |url=http://www.seekwellness.com/conditions/addisons.htm#pregnancy |title=addison's disease |format= |work=}}</ref>
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| Addison's treatment courses by the mother are generally considered safe for baby during pregnancy.
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| == Prognosis ==
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| While treatment solutions for Addison's disease are far from precise, overall long-term prognosis is typically good. Because of individual physiological differences, each person with Addison's must work closely with their physician to adjust their medication dosage and schedule to find the most effective routine. Once this is accomplished (and occasional adjustments must be made from time to time, especially during periods of travel, stress, or other medical conditions), symptomology is usually greatly reduced or occasionally eliminated so long as the person continues their dosage schedule.
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| == See also ==
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| * [[Cushing's syndrome]] | | * [[Cushing's syndrome]] |
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| == References ==
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| <references/>
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| == External links ==
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| * [http://www.mayoclinic.com/health/addisons-disease/DS00361 Overview of Addison's Disease] from the [[Mayo Clinic]]
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| * [http://addisonsdisease.researchtoday.net Addison's Disease Research Today] - monthly online journal summarizing recent primary literature on Addison's disease
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| * [http://www.MedHelp.org/nadf National Adrenal Diseases Foundation]
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| * [http://www.medicinenet.com/addison_disease/article.htm Addison's information from MedicineNet]
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| * [http://www.medhelp.org/www/nadf3.htm "Addison's Disease: The Facts You Need to Know (MedHelp.org)]
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| * [http://www.nvacp.nl/page.php?main=5 The Addison & Cushing International Federation (ACIF)]
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| * [http://www.seekwellness.com/conditions/addisons.htm Addison's disease info from SeekWellness.com]
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| * [http://www.marvistavet.com/html/body_addison_s_disease.html Information about Addison's disease in canines (dogs)]
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| * [http://www.antibodypatterns.com/adrenal.php Antibodies to adrenal gland]
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| * [http://www.ii.bham.ac.uk/clinicalimmunology/CISimagelibrary/Adrenal.htm Immunofluorescence images]
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| * [http://www.endocrine.niddk.nih.gov/ Endocrine and Metabolic Diseases Information Service]
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| === Support groups ===
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| * [http://www.addisons.org.uk Addison's Disease Self Help Group (ADSHG)] - UK support group
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| * [http://www.addisons.org.au Australian Addison's Disease Association] - Australian support and information group
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| * [http://www.nvacp.nl/ Nederlandse Vereniging voor Addison en Cushing Patiënten] - Dutch support and information group with information and documentation in English
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| * [http://www.nvacp.nl/page.php?main=5&sub=58 Addresses of patient organisations and support groups around the world]
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |
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| [[Category:Endocrinology]]
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| [[Category:Medical emergencies]]
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| [[bg:Адисонова болест]] | | [[bg:Адисонова болест]] |
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