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{{Infobox_Disease |
{{Infobox_Disease |
   Name          = Addison's disease |
   Name          = {{PAGENAME}} |
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   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}} |
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   OMIM          = |
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   eMedicineSubj  = |
   eMedicineTopic = 42 |
   eMedicineTopic = |
  MeshID        = D000224 |
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{{Addison's disease}}
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{{Editor Join}}
 
==Overview==
 
'''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.
 
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>
 
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/>
 
== Causes ==
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/>
 
;Adrenal dysgenesis
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/>
 
;Impaired steroidogenesis
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/>
 
;Adrenal destruction
[[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/>
 
== Complete differential diagnosis of causes of Addison's disease <ref>Sailer, Christian, Wasner, Susanne.  Differential Diagnosis Pocket.  Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:14-15</ref> ==
=== Primary Adrenocoritcal Insufficiency (Addison's disease) ===
* Autoimmune/idiopathic
* Congenital
*:* [[Congenital adrenal hyperplasia]]
*:* Familial glucocorticoid deficiency
*:* Adrenal leukodystrophy
*:* Adrenal aplasia/hypoplasia
* Iatrogenic
*:* [[Radiation]] (therapy)
*:* Bilateral adrenalectomy
* Fungal
*:* [[Cryptococcosis]]
*:*:*  [[Histoplasmosis]]
*:* [[Blastomycosis]]
*:* [[Syphilis]]
*:* [[Coccidiomycosis]]
*:* [[Tuberculosis]] (20% of all Addison's)
* Hemorrhage, infarction
*:* [[Trauma]]
*:* Surgery
*:* [[Sepsis]]
*:*:*  [[Waterhouse-Friderichson syndrome]]
*:* [[Embolus]]
*:* Anticoagulation
*:* [[Arteritis]]
*:* [[Hypotension]]
*:* Neonatal
*:* Thrombosis
*:* [[Coagulopathy]]
* Infections
*:* [[AIDS]]
*:*:*  [[Toxoplasmosis]]
*:*:*  [[Kaposi's sarcoma]]
*:*:*  [[CMV]]
*:*:*  [[Mycobacterium avium intracellulaire]] ([[MAI]])
*:*:*  [[Cryptococcosis]]
* Neoplasm
*:* [[Metastases]]
*:* [[Leukemia]]
*:* [[Lymphoma]]
* [[Uremia]]
* [[Coma]]
* Infiltrative
*:* [[Amyloidosis]]
*:* [[Sarcoidosis]]
*:* [[Hemochromatosis]]
* Volume/electrolyte disorders
* [[Drugs]]
 
=== Secondary (pituitary) or Tertiary (hypothalamic) Adrenocortical Insufficiency ===
* Drug withdrawal
* After surgery of [[cortisol]]-secreting tumor
 
==Signs and symptoms==
===Symptoms===
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/>
 
=== Clinical signs===
On examination, the following may be noticed:<ref name=Ten/>
* [[Hypotension|Low blood pressure]] that falls further when standing ([[orthostatic hypotension]])
* 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.
* Signs of conditions that often occur together with Addison's: [[goiter]] and [[vitiligo]]
 
=== Addisonian crisis ===
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.
 
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>
* Sudden penetrating pain in the legs, lower back or abdomen
* Severe vomiting and diarrhea, resulting in [[dehydration]]
* [[Hypotension|Low blood pressure]]
* [[Fainting|Loss of consciousness/Syncope]]
* [[Hypoglycemia]]
* Confusion, psychosis
* [[Seizure|Convulsions]]
 


== Diagnosis ==
'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
=== Suggestive features===
Routine investigations may show:<ref name=Ten/>
* [[Hypoglycemia]], low blood sugar (worse in children)
* [[Hyponatraemia]] (low blood sodium levels)
* [[Hyperkalemia]] (raised blood [[potassium]] levels), due to loss of production of the hormone [[aldosterone]]
* [[Eosinophilia]] and [[lymphocytosis]] (increased number of [[eosinophil]]s or [[lymphocyte]]s, two types of [[white blood cell]]s)


===Testing===
{{CMG}}; {{AE}} {{ADG}}
[[Image:Cortisol-2D-skeletal.png|thumb|[[Cortisol]]]][[Image:Aldosterone-2D-skeletal.png|thumb|[[Aldosterone]]]]
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.


The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (IM/IV) is given. 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.
{{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


The long test uses 1 mg tetracosactide (IM). Blood is taken 1, 4, 8, and 24 hours later.  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 overview|Overview]]==


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 historical perspective|Historical Perspective]]==


==[[Addison's disease pathophysiology|Pathophysiology]]==


==[[Addison's disease causes|Causes]]==


== Treatment ==
==[[Addison's disease differential diagnosis|Differentiating Addison's disease from other Diseases]]==
=== Maintenance treatment===
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.


===Addisonian crisis===
==[[Addison's disease epidemiology and demographics|Epidemiology and Demographics]]==
Treatment for an acute attack, an Addisonian crisis, usually involves intravenous (into blood veins) injections of:
* Cortisone ([[cortisol]])
* Saline solution (basically a salt water, same clear [[Intravenous therapy#Infusion equipment|IV bag]] as used to treat dehydration)
* [[Glucose]]


=== Surgery ===
==[[Addison's disease risk factors|Risk Factors]]==
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.


=== Pregnancy ===
==[[Addison's disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
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>
Addison's treatment courses by the mother are generally considered safe for baby during pregnancy.


== Epidemiology ==
==Diagnosis==
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>
(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>)
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>


== Prognosis ==
[[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]]
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.


== Canine hypoadrenocorticism ==
==Treatment==
The condition is relatively rare, but has been diagnosed in all breeds of dogs. In general, it is underdiagnosed, and one has to have a clinical suspicion of it as an underlying disorder for many presenting complaints. Females are overrepresented, and the disease often appears in middle age (4-7 years), although any age or gender may be affected.
[[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]]


Hypoadrenocorticism is treated with prednisolone and/or fludrocortisone (Florinef (r)) or a monthly injection called Percorten V (desoxycorticosterone pivlate (DOCP)).  Routine blood work is necessary periodically to assess therapy.
==Related Chapter==
 
Most of the medications used in the therapy of hypoadrenocorticism cause excessive thirst and urination. It is absolutely vital to provide fresh drinking water for the canine sufferer.
 
If the owner knows about an upcoming stressful situation (shows, traveling etc.), patients generally need an increased dose of prednisone to help deal with the added stress.  Avoidance of stress is important for dogs with hypoadrenocorticism.
 
== Famous Addisonians ==
* President John F. Kennedy was one of the best-known Addison's disease sufferers.
* Popular singer Helen Reddy.<ref>{{cite web |url=http://www.addisons.org.au/core.htm?page=/awareness/awarenessweek.htm |title=The Australian Addison's Disease Association|format= |work=}}</ref> 
* Scientist Eugene Merle Shoemaker Co-discoverer of the Comet Shoemaker-Levy 9.<ref>{{cite web |url=http://www2.jpl.nasa.gov/sl9/news81.html |title=Eugene Shoemaker (1928-1997)|format= |work=}}</ref>
* French Carmelite nun and religious writer Blessed Elizabeth of the Trinity <ref>{{cite web |url=http://www.catholic-forum.com/saintS/sainte46.htm |title=catholic-forum.com |format= |work=}}</ref>
* Some have suggested that Jane Austen was an ''avant la lettre'' case, but others have disputed this.<ref>{{cite journal |author=Upfal A |title=Jane Austen’s lifelong health problems and final illness: New evidence points to a fatal Hodgkin’s disease and excludes the widely accepted Addison's |journal=J Med Ethics Med Humanities | volume=31 |year=2005 |pages=3-11|url=http://mh.bmj.com/cgi/content/full/31/1/3}}</ref>
* According to Dr. Carl Abbott, a Canadian medical researcher, Charles Dickens may also have been afflicted.<ref name="dickens">{{cite journal | author=L. Williams ''et al.'' | title=The Nineteenth Century: Victorian Period | journal=The Year's Work in English Studies | year=1991 | volume=72 | issue=1 | pages= 314–360 | | url = http://ywes.oxfordjournals.org/cgi/content/long/72/1/314 | doi = 10.1093/ywes/72.1.314 | publisher = Oxford University Press}}</ref>
* Osama bin-Laden - may be an Addisonian: Lawrence Wright (''The Looming Tower'', 2006, p. 139) notes that bin-Laden manifests all the key symptoms: "low blood pressure, weight loss, muscle fatigue, stomach irritability, sharp back pains, dehydration, and an abnormal craving for salt".  Bin-Laden is known to have been consuming large amounts of the drug [[Arcalion]] to treat his symptoms.
 
== See also ==
* [[Cushing's syndrome]]
* [[Cushing's syndrome]]
== References ==
<references/>
* {{cite web | author=National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
| year = 2004 | month =June | url=http://www.niddk.nih.gov/health/endo/pubs/addison/addison.htm  | title =NIH Publication No. 04–3054: Addison's disease | work =Endocrine and Metabolic Diseases Information Service | publisher =National Institute for Health}}
== External links ==
* [http://www.mayoclinic.com/health/addisons-disease/DS00361 Overview of Addison's Disease] from the [[Mayo Clinic]]
* [http://addisonsdisease.researchtoday.net Addison's Disease Research Today] - monthly online journal summarizing recent primary literature on Addison's disease
* [http://www.MedHelp.org/nadf National Adrenal Diseases Foundation]
* [http://www.medicinenet.com/addison_disease/article.htm Addison's information from MedicineNet]
* [http://www.medhelp.org/www/nadf3.htm "Addison's Disease: The Facts You Need to Know (MedHelp.org)]
* [http://www.nvacp.nl/page.php?main=5 The Addison & Cushing International Federation (ACIF)]
* [http://www.seekwellness.com/conditions/addisons.htm Addison's disease info from SeekWellness.com]
* [http://www.marvistavet.com/html/body_addison_s_disease.html Information about Addison's disease in canines (dogs)]
*[http://www.antibodypatterns.com/adrenal.php Antibodies to adrenal gland]
*[http://www.ii.bham.ac.uk/clinicalimmunology/CISimagelibrary/Adrenal.htm Immunofluorescence images]
*[http://www.endocrine.niddk.nih.gov/ Endocrine and Metabolic Diseases Information Service]
=== Support groups ===
* [http://www.addisons.org.uk Addison's Disease Self Help Group (ADSHG)] - UK support group
* [http://www.addisons.org.au Australian Addison's Disease Association] - Australian support and information group
* [http://www.nvacp.nl/ Nederlandse Vereniging voor Addison en Cushing Patiënten] - Dutch support and information group with information and documentation in English
* [http://www.nvacp.nl/page.php?main=5&sub=58 Addresses of patient organisations and support groups around the world]




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Latest revision as of 13:14, 2 October 2017

Addison's disease
Classic hyperpigmentation of Addison's disease;

Source:By FlatOut - Dermatology Online Journal http://dermatology.cdlib.org/, CC0, https://commons.wikimedia.org/w/index.php?curid=25847348

ICD-10 E27.1
ICD-9 255.41
DiseasesDB 76715008

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Synonyms and keywords: 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

Overview

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bg:Адисонова болест cs:Addisonova choroba da:Addisons sygdom de:Nebennierenrindeninsuffizienz it:Morbo di Addison he:מחלת אדיסון ms:Penyakit Addison nl:Ziekte van Addison sk:Addisonova choroba fi:Addisonin tauti sv:Addisons sjukdom

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