Editing Cushing's syndrome

{{Short description|Symptoms from excessive exposure to glucocorticoids such as cortisol}}
{{Hatnote|Not to be confused with [[Cushing's triad]], which is due to increased intracranial pressure.}}
{{About|the disease in humans|the disease in animals|Cushing's syndrome (veterinary)}}
{{Infobox medical condition (new)
| name            = Cushing's syndrome
| synonyms        = Hypercortisolism, Itsenko-Cushing syndrome, hyperadrenocorticism
| image           = CushingsFace.jpg
| caption         = [[Moon face|Facial appearance]] of a 30 year old female patient with iatrogenic Cushing's syndrome<ref name=Cel2012>{{cite journal | vauthors = Celik O, Niyazoglu M, Soylu H, Kadioglu P | title = Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs | journal = Multidisciplinary Respiratory Medicine | volume = 7 | issue = 1 | pages = 26 | date = August 2012 | pmid = 22958272 | pmc = 3436715 | doi = 10.1186/2049-6958-7-26 | doi-access = free }}</ref>
| field           = [[Endocrinology]]
| symptoms        = [[hypertension|High blood pressure]], [[abdominal obesity]] with thin arms and legs, reddish [[stretch mark]]s, [[moon facies|round face]], often reddened due to facial plethora, [[Lipodystrophy|fat lump between the shoulders]], [[Muscle weakness|weak muscles]], [[acne]], fragile skin<ref name=NIH2012Sym/>
| complications   = High blood pressure (hypertension), Type 2 diabetes, Frequent or unusual infections, Loss of muscle mass and strength, Bone loss (osteoporosis).<ref>{{cite web |title=Cushing syndrome |url=https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/syc-20351310 |website=mayoclinic.org |publisher=Mayo Clinic |access-date=June 5, 2022}}</ref>
| onset           = 20–50 years<ref name=NIH2008/>
| duration        =
| causes          = Prolonged exposure to [[cortisol]]<ref name=NIH2008/>
| risks           =
| diagnosis       = Requires a number of steps<ref name=NIH2012Diag/>
| differential    =
| prevention      =
| treatment       = Based on underlying cause<ref name=NIH2012Tx2/>
| medication      =
| prognosis       = Generally good with treatment<ref name=NIH2012Tx/>
| frequency       = 2–3 per million people per year<ref name=NIH2012Epi/> (from 1/333,333 to 1/500,000 people)
| deaths          =
}}

<!-- Definition and symptoms -->
'''Cushing's syndrome''' is a collection of signs and symptoms due to prolonged exposure to [[glucocorticoids]] such as [[cortisol]].<ref name="NIH2008">{{cite web|title=Cushing's Syndrome|url=http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#1|publisher=National Endocrine and Metabolic Diseases Information Service (NEMDIS)|access-date=16 March 2015|date=July 2008|url-status=dead|archive-url=https://web.archive.org/web/20150210104139/http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#1|archive-date=10 February 2015}}</ref><ref>{{cite book| vauthors = Forbis P |title=Stedman's medical eponyms|date=2005|publisher=Lippincott Williams & Wilkins|location=Baltimore, Md.|isbn=9780781754439|page=167|edition=2nd|url=https://books.google.com/books?id=isqcnR6ryz0C&pg=PA167|url-status=live|archive-url=https://web.archive.org/web/20170908153203/https://books.google.com/books?id=isqcnR6ryz0C&pg=PA167|archive-date=2017-09-08}}</ref><ref name="Shar2011">{{cite journal | vauthors = Sharma ST, Nieman LK | title = Cushing's syndrome: all variants, detection, and treatment | journal = Endocrinology and Metabolism Clinics of North America | volume = 40 | issue = 2 | pages = 379–91, viii–ix | date = June 2011 | pmid = 21565673 | pmc = 3095520 | doi = 10.1016/j.ecl.2011.01.006 }}</ref> Signs and symptoms may include [[hypertension|high blood pressure]], [[abdominal obesity]] but with thin arms and legs, reddish [[stretch mark]]s, a [[moon face|round red face]] due to [[Plethora (medicine)#Facial plethora|facial plethora]],<ref name="Afshari">{{cite journal |last1=Afshari |first1=A |last2=Ardeshirpour |first2=Y |last3=Lodish |first3=MB |title=Facial Plethora: Modern Technology for Quantifying an Ancient Clinical Sign and Its Use in Cushing Syndrome. |journal=The Journal of Clinical Endocrinology and Metabolism |date=October 2015 |volume=100 |issue=10 |pages=3928–33 |doi=10.1210/jc.2015-2497 |pmid=26301943|pmc=4596033 }}</ref> a [[Lipodystrophy|fat lump between the shoulders]], [[Muscle weakness|weak muscles]], [[osteoporosis|weak bones]], [[acne]], and fragile skin that heals poorly.<ref>{{Cite journal |last1=Patel |first1=Reema |last2=Sherf |first2=Sahar |last3=Lai |first3=Ngan Betty |last4=Yu |first4=Run |date=2022-11-01 |title=Exogenous Cushing Syndrome Caused by a "Herbal" Supplement |url=https://www.aaceclinicalcasereports.com/article/S2376-0605(22)00051-7/abstract |journal=AACE Clinical Case Reports |language=English |volume=8 |issue=6 |pages=239–242 |doi=10.1016/j.aace.2022.08.001 |pmid=36447831 |pmc=9701910 |issn=2376-0605}}</ref><ref name="NIH2012Sym" /> Women may have [[hirsutism|more hair]] and irregular menstruation or loss of menses, with the exact mechanisms of why still unknown.<ref>{{cite journal | pmc=11301536 | date=2024 | last1=Alhajeri | first1=A. | last2=Hajji | first2=S. | last3=Aljenaee | first3=K. | title=Amenorrhea as a presentation of Cushing's syndrome | journal=Endocrinology, Diabetes & Metabolism Case Reports | issue=3 | pages=23–0152 | doi=10.1530/EDM-23-0152 | pmid=39042723 }}</ref><ref name="NIH2012Sym" /> Occasionally there may be changes in mood, [[headache]]s, and a [[fatigue (medical)|chronic feeling of tiredness]].<ref name="NIH2012Sym">{{cite web|title=What are the symptoms of Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/symptoms.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402183051/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/symptoms.aspx|archive-date=2 April 2015}}</ref>

<!-- Cause and diagnosis -->
Cushing's syndrome is caused by either excessive cortisol-like medication, such as [[prednisone]], or a [[tumor]] that either produces or results in the production of excessive cortisol by the [[adrenal gland]]s.<ref name=NIH2012Cause>{{cite web|title=What causes Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/causes.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402193822/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/causes.aspx|archive-date=2 April 2015}}</ref> Cases due to a [[pituitary adenoma]] are known as [[Cushing's disease]], which is the second most common cause of Cushing's syndrome after medication.<ref name=NIH2008/> A number of other tumors, often referred to as ectopic due to their placement outside the pituitary, may also cause Cushing's.<ref name=NIH2008/><ref>{{cite journal | vauthors = Nieman LK, Ilias I | title = Evaluation and treatment of Cushing's syndrome | journal = The American Journal of Medicine | volume = 118 | issue = 12 | pages = 1340–1346 | date = December 2005 | pmid = 16378774 | doi = 10.1016/j.amjmed.2005.01.059 | url = https://zenodo.org/record/1258724 }}</ref> Some of these are associated with [[hereditary|inherited]] disorders such as [[multiple endocrine neoplasia type 1]] and [[Carney complex]].<ref name=NIH2012Epi/> Diagnosis requires a number of steps.<ref name=NIH2012Diag>{{cite web|title=How do health care providers diagnose Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/diagnosed.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402162423/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/diagnosed.aspx|archive-date=2 April 2015}}</ref> The first step is to check the medications a person takes.<ref name=NIH2012Diag/> The second step is to measure levels of cortisol in the [[urine]], [[saliva]] or in the [[blood]] after taking [[dexamethasone suppression test|dexamethasone]].<ref name=NIH2012Diag/> If this test is abnormal, the cortisol may be measured late at night.<ref name=NIH2012Diag/> If the cortisol remains high, a blood test for [[ACTH]] may be done.<ref name=NIH2012Diag/>

<!-- Treatment -->
Most cases can be treated and cured.<ref name="NIH2012Tx">{{cite web|title=Is there a cure for Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/cure.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150327103924/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/cure.aspx|archive-date=27 March 2015}}</ref> If brought on by medications, these can often be slowly decreased if still required or slowly stopped.<ref name="NIH2012Tx2">{{cite web|title=What are the treatments for Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/treatments.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402102535/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/treatments.aspx|archive-date=2 April 2015}}</ref><ref name=Mayo2019>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/diagnosis-treatment/drc-20351314|title=Cushing syndrome - Diagnosis and treatment - Mayo Clinic|website=www.mayoclinic.org|access-date=2019-04-21}}</ref> If caused by a tumor, it may be treated by a combination of surgery, [[chemotherapy]], and/or [[radiation therapy|radiation]].<ref name="NIH2012Tx2" /> If the pituitary was affected, other medications may be required to replace its lost function.<ref name="NIH2012Tx2" /> With treatment, life expectancy is usually normal.<ref name="NIH2012Tx" /> Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.<ref>{{cite journal | vauthors = Graversen D, Vestergaard P, Stochholm K, Gravholt CH, Jørgensen JO | title = Mortality in Cushing's syndrome: a systematic review and meta-analysis | journal = European Journal of Internal Medicine | volume = 23 | issue = 3 | pages = 278–282 | date = April 2012 | pmid = 22385888 | doi = 10.1016/j.ejim.2011.10.013 }}</ref>

<!-- Epidemiology, history, and other animals -->
About two to three cases per million persons are caused overtly by a tumor.<ref name=NIH2012Epi/> It most commonly affects people who are 20 to 50 years of age.<ref name=NIH2008/> Women are affected three times more often than men.<ref name=NIH2012Epi>{{cite web|title=How many people are affected by or at risk for Cushing's syndrome?|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/risk.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402220131/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/risk.aspx|archive-date=2 April 2015}}</ref> A mild degree of overproduction of cortisol without obvious symptoms, however, is more common.<ref>{{cite journal | vauthors = Steffensen C, Bak AM, Rubeck KZ, Jørgensen JO | title = Epidemiology of Cushing's syndrome | journal = Neuroendocrinology | volume = 92 | pages = 1–5 | date = 2010 | issue = Suppl 1 | pmid = 20829610 | doi = 10.1159/000314297 | doi-access = free }}</ref> Cushing's syndrome was first described by American neurosurgeon [[Harvey Cushing]] in 1932.<ref>{{cite web|title=Cushing Syndrome: Condition Information|url=http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/Pages/default.aspx|access-date=16 March 2015|date=2012-11-30|url-status=live|archive-url=https://web.archive.org/web/20150402193912/http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/Pages/default.aspx|archive-date=2 April 2015}}</ref> Cushing's syndrome may also occur in other animals including cats, dogs, and horses.<ref>{{cite book|author1=Etienne Cote|title=Clinical Veterinary Advisor: Dogs and Cats|date=2014|publisher=Elsevier Health Sciences|isbn=9780323240741|page=502|edition=3|url=https://books.google.com/books?id=NmziBQAAQBAJ&pg=PA502|url-status=live|archive-url=https://web.archive.org/web/20170908153203/https://books.google.com/books?id=NmziBQAAQBAJ&pg=PA502|archive-date=2017-09-08}}</ref><ref>{{cite journal | vauthors = McCue PM | title = Equine Cushing's disease | journal = The Veterinary Clinics of North America: Equine Practice | volume = 18 | issue = 3 | pages = 533–43, viii | date = December 2002 | pmid = 12516933 | doi = 10.1016/s0749-0739(02)00038-x }}</ref>

==Signs and symptoms==
[[File:Cushing syndrome svg hariadhi.svg|thumb|300px|upright=1.4|Symptoms of Cushing's syndrome<ref>{{cite web|url=http://www.mayoclinic.org/diseases-conditions/cushing-syndrome/basics/symptoms/con-20032115|title=Cushing syndrome|publisher=[[Mayo Clinic]]|date=March 28, 2013|access-date=2015-05-25|url-status=live|archive-url=https://web.archive.org/web/20150525104806/http://www.mayoclinic.org/diseases-conditions/cushing-syndrome/basics/symptoms/con-20032115|archive-date=May 25, 2015}}</ref>]] [[File:CushingsBody.jpg|thumb|[[Hirsutism|Increased hair]] and [[stria]] in a 30-year-old female patient with iatrogenic Cushing's syndrome<ref name=Cel2012/>]]
[[File:BabyCushing.png|thumb|Features of Cushing syndrome including a round face, acne, reddish skin, central obesity, and poor muscle tone<ref>{{cite journal | vauthors = Fudge EB, von Allmen D, Volmar KE, Calikoglu AS | title = Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor | journal = International Journal of Pediatric Endocrinology | volume = 2009 | pages = 168749 | date = 2009 | pmid = 20049152 | pmc = 2798106 | doi = 10.1155/2009/168749 | doi-access = free }}</ref>]]

Symptoms include rapid [[obesity|weight gain]], particularly of the trunk and face with sparing of the limbs ([[central obesity]]). Common signs include the growth of fat pads along the [[clavicle|collarbone]], on the back of the neck ("buffalo hump" or [[lipodystrophy]]), and on the face ("[[moon face]]"). Other symptoms include [[hyperhidrosis|excess sweating]], [[telangiectasia|dilation of capillaries]], thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red [[Stretch marks|striae]] (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and [[hirsutism]] (facial male-pattern hair growth), [[baldness]] and/or extremely dry and brittle hair. In rare cases, Cushing's can cause [[hypocalcemia]]. The excess cortisol may also affect other endocrine systems and cause, for example, [[insomnia]], inhibited [[aromatase]], reduced [[libido]], [[impotence]] in men, and [[amenorrhoea]], [[oligomenorrhea]] and [[infertility]] in women due to elevations in [[androgens]]. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of [[GnRH]] release.<ref name="pmid9745407">{{cite journal | vauthors = Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, Perry LA, Grossman AB, Besser GM, Trainer PJ | title = Menstrual abnormalities in women with Cushing's disease are correlated with hypercortisolemia rather than raised circulating androgen levels | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 83 | issue = 9 | pages = 3083–3088 | date = September 1998 | pmid = 9745407 | doi = 10.1210/jcem.83.9.5084 | doi-access = free }}</ref>

Many of the features of Cushing's are those seen in [[metabolic syndrome]], including [[insulin resistance]], [[hypertension]], [[obesity]], and elevated blood levels of [[triglyceride]]s.<ref name="pmid20829625 ">{{cite journal | vauthors = Arnaldi G, Scandali VM, Trementino L, Cardinaletti M, Appolloni G, Boscaro M | title = Pathophysiology of dyslipidemia in Cushing's syndrome | journal = Neuroendocrinology | volume = 92 | issue = Suppl 1 | pages = 86–90 | year = 2010 | pmid = 20829625 | doi = 10.1159/000314213 | doi-access = free | hdl = 10447/620731 | hdl-access = free }}</ref>

Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol,<ref>{{cite journal | vauthors = Belanoff JK, Gross K, Yager A, Schatzberg AF | title = Corticosteroids and cognition | journal = Journal of Psychiatric Research | volume = 35 | issue = 3 | pages = 127–145 | year = 2001 | pmid = 11461709 | doi = 10.1016/s0022-3956(01)00018-8 }}</ref> and may be early indicators of exogenous or endogenous Cushing's. [[clinical depression|Depression]] and [[anxiety disorders]] are also common.<ref>{{cite book |title=The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences | vauthors = Yudofsky SC, Hales RE |edition=5th |year=2007 |publisher=American Psychiatric Pub, Inc. |isbn=978-1-58562-239-9 }}</ref>

Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial fungus ([[dermatophyte]] and [[malassezia]]) infections, and the characteristic purplish, atrophic striae on the abdomen.<ref name="Andrews">{{cite book | vauthors = James W, Berger T, Elston D | date = 2005 | title = Andrews' Diseases of the Skin: Clinical Dermatology | edition = 10th | publisher = Saunders | isbn = 0-7216-2921-0 }}</ref>{{rp|500}}

Other signs include [[polyuria|increased urination]] (and accompanying [[polydipsia|increased thirst]]), persistent [[hypertension|high blood pressure]] (due to cortisol's enhancement of [[epinephrine]]'s vasoconstrictive effect) and [[insulin resistance]] (especially common with ACTH production outside the pituitary), leading to [[hyperglycemia|high blood sugar]] and insulin resistance which can lead to [[diabetes mellitus]].  Insulin resistance is accompanied by skin changes such as [[acanthosis nigricans]] in the [[axilla]] and around the neck, as well as [[skin tag]]s in the axilla. Untreated Cushing's syndrome can lead to [[heart disease]] and increased [[death|mortality]]. Cortisol can also exhibit [[mineralocorticoid]] activity in high concentrations, worsening the hypertension and leading to [[hypokalemia]] (common in ectopic ACTH secretion) and [[hypernatremia]] (increased Na+ ions concentration in plasma). Furthermore, excessive cortisol may lead to [[Human gastrointestinal tract|gastrointestinal]] disturbances, opportunistic infections, and impaired wound healing related to cortisol's suppression of the immune and inflammatory responses. [[Osteoporosis]] is also an issue in Cushing's syndrome since osteoblast activity is inhibited. Additionally, Cushing's syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back.{{citation needed|date=August 2020}}

Brain changes such as cerebral atrophy may occur.<ref>{{cite journal | vauthors = Andela CD, van Haalen FM, Ragnarsson O, Papakokkinou E, Johannsson G, Santos A, Webb SM, Biermasz NR, van der Wee NJ, Pereira AM | display-authors = 6 | title = MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies | journal = European Journal of Endocrinology | volume = 173 | issue = 1 | pages = R1-14 | date = July 2015 | pmid = 25650405 | doi = 10.1530/EJE-14-1101 | doi-access = free | hdl = 1887/118098 | hdl-access = free }}</ref> This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and correlates highly with psychopathological personality changes.<ref name="DornBurgess1997">{{cite journal | vauthors = Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP | title = The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 82 | issue = 3 | pages = 912–919 | date = March 1997 | pmid = 9062506 | doi = 10.1210/jcem.82.3.3834 | doi-access = free }}</ref><ref name="CopeShane2012">{{cite journal | vauthors = Cope LM, Shane MS, Segall JM, Nyalakanti PK, Stevens MC, Pearlson GD, Calhoun VD, Kiehl KA | display-authors = 6 | title = Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample | journal = Psychiatry Research | volume = 204 | issue = 2–3 | pages = 91–100 | date = November 2012 | pmid = 23217577 | pmc = 3536442 | doi = 10.1016/j.pscychresns.2012.10.004 }}</ref><ref name="WolkowitzLupien2007">{{cite journal | vauthors = Wolkowitz OM, Lupien SJ, Bigler ED | title = The "steroid dementia syndrome": a possible model of human glucocorticoid neurotoxicity | journal = Neurocase | volume = 13 | issue = 3 | pages = 189–200 | date = June 2007 | pmid = 17786779 | doi = 10.1080/13554790701475468 | s2cid = 39340010 }}</ref><ref name="WeberHabel2008">{{cite journal | vauthors = Weber S, Habel U, Amunts K, Schneider F | title = Structural brain abnormalities in psychopaths-a review | journal = Behavioral Sciences & the Law | volume = 26 | issue = 1 | pages = 7–28 | year = 2008 | pmid = 18327824 | doi = 10.1002/bsl.802 }}</ref>

Additional symptoms may include:

* Rapid weight gain
* Moodiness, irritability, or depression
* Muscle and bone weakness
* Memory and attention dysfunction
* [[Osteoporosis]]
* [[Diabetes mellitus]]
* [[Hypertension]]
* Immune suppression
* Sleep disturbances
* Menstrual disorders such as [[amenorrhea]] in women
* [[Infertility]] in women
* [[Impotence]] in men
* [[Hirsutism]]
* [[Baldness]]
* [[Hypercholesterolemia]]

=== Hyperpigmentation ===
Cushing's syndrome due to excess [[ACTH]] may also result in [[hyperpigmentation]]. This is due to [[melanocyte-stimulating hormone]] production as a byproduct of ACTH synthesis from pro-opiomelanocortin (POMC). Alternatively, it is proposed that the high levels of ACTH, [[β-lipotropin]], and [[lipotropin|γ-lipotropin]], which contain weak MSH function, can act on the [[melanocortin 1 receptor]]. A variant of Cushing's disease can be caused by ectopic, i.e. extra pituitary, ACTH production from, for example, a small-cell lung cancer.<ref name="auto">{{cite web |url=https://www.lecturio.com/concepts/cushings-syndrome/| title=Cushing's Syndrome
|website=The Lecturio Medical Concept Library |access-date= 11 July 2021}}</ref>

When Cushing's syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), [[negative feedback]] ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops.<ref name="auto"/>

==Causes==
Cushing's syndrome may result from any cause of increased glucocorticoid levels, whether due to medication or internal processes.<ref name=Shar2011/><ref name = "Chaudhry_2019">{{cite book | vauthors = Chaudhry HS, Singh G | chapter =Cushing Syndrome|date=2019|chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK470218/| title = StatPearls|publisher=StatPearls Publishing|pmid=29261900|access-date=2019-04-20 }}</ref> Some sources however do not consider the glucocorticoid medication-induced condition as "Cushing's syndrome" proper, instead using the term "Cushingoid" to describe the medication's side effects which mimic the endogenous condition.<ref name=":0">{{cite journal | vauthors = Baek JH, Kim SK, Jung JH, Hahm JR, Jung J | title = Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency | journal = Endocrinology and Metabolism | volume = 31 | issue = 1 | pages = 153–160 | date = March 2016 | pmid = 26676337 | pmc = 4803552 | doi = 10.3803/EnM.2016.31.1.153 }}</ref><ref name = "Chaudhry_2019" /><ref>{{cite journal | vauthors = Nieman LK | title = Cushing's syndrome: update on signs, symptoms and biochemical screening | journal = European Journal of Endocrinology | volume = 173 | issue = 4 | pages = M33–M38 | date = October 2015 | pmid = 26156970 | pmc = 4553096 | doi = 10.1530/EJE-15-0464 }}</ref>

[[Cushing's disease]] is a specific type of Cushing's syndrome caused by a pituitary tumor leading to excessive production of [[ACTH]] (adrenocorticotropic hormone). Excessive ACTH stimulates the [[adrenal cortex]] to produce high levels of cortisol, producing the disease state. While all Cushing's disease gives Cushing's syndrome, not all Cushing's syndrome is due to Cushing's disease.<ref>Lynnette K. Nieman, Beverly M. K. Biller, James W. Findling, John Newell-Price, Martin O. Savage, Paul M. Stewart, Victor M. Montori,  The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline, ''The Journal of Clinical Endocrinology & Metabolism'', Volume 93, Issue 5, 1 May 2008, Pages 1526–1540,</ref> Several possible causes of Cushing's syndrome are known including the taking of herbal supplements over-the-counter that do not list glucocorticoids in their ingredients.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2022-10-31 |title=Public Notification: Artri King contains hidden drug ingredients |url=https://www.fda.gov/drugs/medication-health-fraud/public-notification-artri-king-contains-hidden-drug-ingredients |journal=FDA |language=en}}</ref><ref>{{Cite journal |last1=Patel |first1=Reema |last2=Sherf |first2=Sahar |last3=Lai |first3=Ngan Betty |last4=Yu |first4=Run |date=2022-11-01 |title=Exogenous Cushing Syndrome Caused by a "Herbal" Supplement |url=https://www.aaceclinicalcasereports.com/article/S2376-0605(22)00051-7/abstract |journal=AACE Clinical Case Reports |language=English |volume=8 |issue=6 |pages=239–242 |doi=10.1016/j.aace.2022.08.001 |pmid=36447831 |pmc=9701910 |issn=2376-0605}}</ref>

===Exogenous===
The most common cause of Cushing's syndrome is the use of prescribed [[glucocorticoid]]s to treat other diseases ([[iatrogenesis|iatrogenic]] Cushing's syndrome). Glucocorticoids are used in treatment of a variety of disorders, including [[asthma]] and [[rheumatoid arthritis]], and also used for [[immunosuppression]] after organ transplants. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Rarely, Cushing's syndrome can also be due to the use of [[medroxyprogesterone acetate]].<ref name="pmid2552887">{{cite journal | vauthors = Siminoski K, Goss P, Drucker DJ | title = The Cushing syndrome induced by medroxyprogesterone acetate | journal = Annals of Internal Medicine | volume = 111 | issue = 9 | pages = 758–760 | date = November 1989 | pmid = 2552887 | doi = 10.7326/0003-4819-111-9-758 }}</ref><ref>{{cite journal | vauthors = Merrin PK, Alexander WD | title = Cushing's syndrome induced by medroxyprogesterone | journal = BMJ | volume = 301 | issue = 6747 | pages = 345 | date = August 1990 | pmid = 2144198 | pmc = 1663616 | doi = 10.1136/bmj.301.6747.345-a }}</ref> In exogenous Cushing's, the adrenal glands may often gradually atrophy due to lack of stimulation by ACTH, the production of which is suppressed by glucocorticoid medication. Abruptly stopping the medication can thus result in acute and potentially life-threatening [[adrenal insufficiency]] and the dose must hence be slowly and carefully tapered off to allow internal cortisol production to pick up. In some cases, patients never recover sufficient levels of internal production and must continue taking glucocorticoids at physiological doses for life.<ref name=":0" /><ref>{{cite journal | vauthors = Broersen LH, Pereira AM, Jørgensen JO, Dekkers OM | title = Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 6 | pages = 2171–2180 | date = June 2015 | pmid = 25844620 | doi = 10.1210/jc.2015-1218 | doi-access = free }}</ref>

Cushing's syndrome in childhood is especially rare; it usually results from use of glucocorticoid medication.<ref name="pmid23099271">{{cite journal | vauthors = Stratakis CA | title = Cushing syndrome in pediatrics | journal = Endocrinology and Metabolism Clinics of North America | volume = 41 | issue = 4 | pages = 793–803 | date = December 2012 | pmid = 23099271 | pmc = 3594781 | doi = 10.1016/j.ecl.2012.08.002 }}</ref>

=== Endogenous ===
[[Endogeny|Endogenous]] Cushing's syndrome results from some derangement of the body's own system of cortisol secretion. Normally, [[ACTH]] is released from the [[pituitary gland]] when necessary to stimulate the release of cortisol from the [[adrenal gland]]s.{{cn|date=October 2021}}

* In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This is also known as [[Cushing's disease]] and is responsible for 70% of endogenous Cushing's syndrome.<ref name="endocrine.niddk">[http://endocrine.niddk.nih.gov/pubs/cushings/cushings.htm#1 Cushing's Syndrome] {{webarchive|url=https://web.archive.org/web/20110410084418/http://endocrine.niddk.nih.gov/pubs/cushings/cushings.htm |date=2011-04-10 }} at The National Endocrine and Metabolic Diseases Information Service. July 2008. Citing: * {{cite journal | vauthors = Nieman LK, Ilias I | title = Evaluation and treatment of Cushing's syndrome | journal = The American Journal of Medicine | volume = 118 | issue = 12 | pages = 1340–1346 | date = December 2005 | pmid = 16378774 | doi = 10.1016/j.amjmed.2005.01.059 | url = https://zenodo.org/record/1258724 }}</ref>
* In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.
* Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or [[paraneoplasia|paraneoplastic]] Cushing's disease and is seen in diseases such as [[small cell carcinoma|small cell]] [[lung cancer]].<ref name="pmid3525603">{{cite journal | vauthors = Schteingart DE, Lloyd RV, Akil H, Chandler WF, Ibarra-Perez G, Rosen SG, Ogletree R | title = Cushing's syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 63 | issue = 3 | pages = 770–775 | date = September 1986 | pmid = 3525603 | doi = 10.1210/jcem-63-3-770 }}</ref>
* Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.<ref name="Voyadzis JM, Guttman-Bauman I, Santi M, Cogen P. 2004 212–6">{{cite journal | vauthors = Voyadzis JM, Guttman-Bauman I, Santi M, Cogen P | title = Hypothalamic hamartoma secreting corticotropin-releasing hormone. Case report | journal = Journal of Neurosurgery | volume = 100 | issue = 2 Suppl Pediatrics | pages = 212–216 | date = February 2004 | pmid = 14758953 | doi = 10.3171/ped.2004.100.2.0212 }}</ref>

===Pseudo-Cushing's syndrome===
Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone, leading to [[pseudo-Cushing's syndrome]]. Estrogen can cause an increase of [[transcortin|cortisol-binding globulin]] and thereby cause the total cortisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24-hour urine collection for urinary free cortisol, is normal.<ref>{{cite journal | vauthors = Katz J | title = Motive to sin | journal = Nature | volume = 359 | issue = 6398 | pages = 769 | date = October 1992 | pmid = 1436049 | pmc = 1436049 | doi = 10.1136/jcp.s1-3.1.11 | bibcode = 1992Natur.359..769K }}</ref>

==Pathophysiology==
The [[hypothalamus]] is in the brain and the [[pituitary gland]] sits just below it. The paraventricular nucleus (PVN) of the hypothalamus releases [[corticotropin-releasing hormone]] (CRH), which stimulates the pituitary gland to release adrenocorticotropin ([[ACTH]]).  ACTH travels via the blood to the adrenal gland, where it stimulates the release of [[cortisol]]. Cortisol is secreted by the cortex of the [[adrenal gland]] from a region called the [[zona fasciculata]] in response to ACTH. Elevated levels of cortisol exert [[negative feedback]] on CRH in the hypothalamus, which decreases the amount of ACTH released from the anterior pituitary gland.{{citation needed|date=August 2020}}

Strictly, Cushing's syndrome refers to excess cortisol of any etiology (as [[syndrome]] means a group of symptoms). One of the causes of Cushing's syndrome is a cortisol-secreting adenoma in the cortex of the adrenal gland (primary hypercortisolism/hypercorticism). The adenoma causes cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low.{{citation needed|date=August 2020}}

[[Cushing's disease]] refers only to hypercortisolism secondary to excess production of ACTH from a corticotroph [[pituitary adenoma]] (secondary hypercortisolism/hypercorticism) or due to excess production of hypothalamus CRH ([[Corticotropin releasing hormone]]) (tertiary hypercortisolism/hypercorticism). This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because the tumor is unresponsive to negative feedback from high cortisol levels.{{cn|date=October 2021}}

When Cushing's syndrome is due to extra [[ACTH]] it is known as ectopic Cushing syndrome.<ref>[https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001443/ Ectopic Cushing syndrome] {{webarchive|url=https://web.archive.org/web/20131002064759/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001443/ |date=2013-10-02 }} at A.D.A.M. Medical Encyclopedia, PubMedHealth, National Institute of Health</ref> This may be seen in a [[paraneoplastic syndrome]].

When Cushing's syndrome is suspected, either a [[dexamethasone suppression test]] (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offers equal detection rates.<ref name="pmid12809455">{{cite journal | vauthors = Raff H, Findling JW | title = A physiologic approach to diagnosis of the Cushing syndrome | journal = Annals of Internal Medicine | volume = 138 | issue = 12 | pages = 980–991 | date = June 2003 | pmid = 12809455 | doi = 10.7326/0003-4819-138-12-200306170-00010 | s2cid = 14930007 }}</ref> Dexamethasone is a [[glucocorticoid]] and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, cortisol levels >50 nmol/L (1.81&nbsp;μg/dL) would be indicative of Cushing's syndrome because an ectopic source of cortisol or ACTH (such as adrenal adenoma) exists which is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in [[saliva]] over 24 hours, which may be equally sensitive, as late-night levels of salivary cortisol are high in cushingoid patients. Other pituitary hormone levels may need to be ascertained.  Performing a [[physical examination]] to determine any [[visual field]] defect may be necessary if a pituitary lesion is suspected, which may compress the [[optic chiasm]], causing typical [[bitemporal hemianopia]].{{citation needed|date=August 2020}}

When any of these tests is positive, [[CT scan]]ning of the adrenal gland and [[MRI]] of the [[pituitary gland]] are performed to detect the presence of any adrenal or pituitary adenomas or [[incidentaloma]]s (the incidental discovery of harmless lesions). [[Scintigraphy]] of the adrenal gland with [[iodocholesterol]] scan is occasionally necessary. Occasionally, determining the ACTH levels in various veins in the body by venous catheterization, working towards the pituitary ([[Inferior petrosal sinus|petrosal sinus]] sampling) is necessary. In many cases, the tumors causing Cushing's disease are less than 2&nbsp;mm in size and difficult to detect using MRI or CT imaging. In one study of 261 patients with confirmed pituitary Cushing's disease, only 48% of pituitary lesions were identified using MRI prior to surgery.<ref>{{cite journal | vauthors = Jagannathan J, Smith R, DeVroom HL, Vortmeyer AO, Stratakis CA, Nieman LK, Oldfield EH | title = Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease | journal = Journal of Neurosurgery | volume = 111 | issue = 3 | pages = 531–539 | date = September 2009 | pmid = 19267526 | pmc = 2945523 | doi = 10.3171/2008.8.JNS08339 }}</ref>

Plasma CRH levels are inadequate at diagnosis (with the possible exception of tumors secreting CRH) because of peripheral dilution and binding to [[CRHBP]].<ref>{{cite book| veditors = Blevins LS |title=Cushing's syndrome|year=2002|publisher=Kluwer Academic|location=Boston|isbn=978-1-4020-7131-7|page=115}}</ref>

==Diagnosis==
[[File:Diagnostic algorithm of suspected Cushing's syndrome.png|thumb|upright|Diagnostic algorithm of suspected Cushing's syndrome:<ref name=Fleseriu2021>{{cite journal |vauthors=Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR | display-authors=etal| title=Consensus on diagnosis and management of Cushing's disease: a guideline update. | journal=Lancet Diabetes Endocrinol | year= 2021 | volume= 9 | issue= 12 | pages= 847–875 | pmid=34687601 | doi=10.1016/S2213-8587(21)00235-7 | pmc=8743006 }}</ref><br>ACTH=adrenocorticotropic hormone.<br>CBG=corticosteroid-binding globulin.<br>CRH=corticotropin-releasing hormone.<br>DST=dexamethasone suppression test.<br>IPSS=inferior petrosal sinus sampling.<br>UFC=urinary free cortisol.<br>*There is consensus that all patients with lesions smaller than 6 mm in diameter should have IPSS and those with lesions of ≥10 mm do not need IPSS, but expert opinions differed for lesions 6–9 mm in diameter.<br>†This alternative option does not have clear consensus and needs further research, and this is indicated by darker boxes.<br>Green boxes indicate points to consider<br>Darker colors indicate less
validated testing pathways.]]

The 24-hour urine-free cortisol test, the low-dose dexamethasone suppression test, and the measurement of midnight plasma cortisol or late-night salivary cortisol are the three primary tests used to diagnose Cushing's syndrome.<ref name="Lancet 2006">{{cite journal | last1=Newell-Price | first1=John | last2=Bertagna | first2=Xavier | last3=Grossman | first3=Ashley B | last4=Nieman | first4=Lynnette K | title=Cushing's syndrome | journal=The Lancet | publisher=Elsevier BV | volume=367 | issue=9522 | year=2006 | issn=0140-6736 | doi=10.1016/s0140-6736(06)68699-6 | pages=1605–1617| pmid=16698415 }}</ref>

Hypercortisolism is related with routine chemistry abnormalities such as neutrophilic leucocytosis, hyperglycemia, hypokalaemia, hypercholesterolemia, and hypercoagulability.<ref name="Lancet 2001">{{cite journal | last1=Boscaro | first1=Marco | last2=Barzon | first2=Luisa | last3=Fallo | first3=Francesco | last4=Sonino | first4=Nicoletta | title=Cushing's syndrome | journal=The Lancet | publisher=Elsevier BV | volume=357 | issue=9258 | year=2001 | issn=0140-6736 | doi=10.1016/s0140-6736(00)04172-6 | pages=783–791| pmid=11253984 }}</ref>

Urinary cortisol levels directly reflect circulating free cortisol.<ref name="Lancet 2006"/> Excess cortisol saturates binding proteins and is eliminated in urine as free cortisol, making it a helpful diagnostic for hypercortisolemia.<ref name="Diagnostic Tests">{{cite journal | last=Kaye | first=Todd B. | title=The Cushing Syndrome: An Update on Diagnostic Tests | journal=Annals of Internal Medicine | publisher=American College of Physicians | volume=112 | issue=6 | date=1990-03-15 | pages=434–444 | issn=0003-4819 | doi=10.7326/0003-4819-76-3-112-6-434 | pmid=2178536 }}</ref> Values four times higher than the top range of normal are uncommon, especially in Cushing's disease.<ref name="Glucocorticoid Action">{{cite journal | last1=Yanovski | first1=Jack A. | last2=Cutler | first2=Gordon B. | title=Glucocorticoid Action and the Clinical Features of Cushing's Syndrome | journal=Endocrinology and Metabolism Clinics of North America | publisher=Elsevier BV | volume=23 | issue=3 | year=1994 | issn=0889-8529 | doi=10.1016/s0889-8529(18)30080-x | pages=487–509| pmid=7805650 }}</ref> A single measurement lacks sensitivity for people with intermittent hypercortisolemia.<ref name="Arnaldi Angeli Atkinson Bertagna 2003 pp. 5593–5602">{{cite journal | last1=Arnaldi | first1=G. | last2=Angeli | first2=A. | last3=Atkinson | first3=A. B. | last4=Bertagna | first4=X. | last5=Cavagnini | first5=F. | last6=Chrousos | first6=G. P. | last7=Fava | first7=G. A. | last8=Findling | first8=J. W. | last9=Gaillard | first9=R. C. | last10=Grossman | first10=A. B. | last11=Kola | first11=B. | last12=Lacroix | first12=A. | last13=Mancini | first13=T. | last14=Mantero | first14=F. | last15=Newell-Price | first15=J. | last16=Nieman | first16=L. K. | last17=Sonino | first17=N. | last18=Vance | first18=M. L. | last19=Giustina | first19=A. | last20=Boscaro | first20=M. | title=Diagnosis and Complications of Cushing's Syndrome: A Consensus Statement | journal=The Journal of Clinical Endocrinology & Metabolism | publisher=The Endocrine Society | volume=88 | issue=12 | year=2003 | issn=0021-972X | doi=10.1210/jc.2003-030871 | pages=5593–5602| pmid=14671138 }}</ref>

==Treatment==
[[File:Management algorithm of Cushing's disease.png|thumb|Management algorithm of Cushing's disease:<ref name=Fleseriu2021/><br>DST=dexamethasone suppression test.<br>IPSS=inferior petrosal sinus sampling.<br>ACTH=adrenocorticotropic hormone.<br>*Pituitary surgery should be performed by an experienced surgeon.<br>†Absence of ACTH-staining adenoma.<br>‡See table 2 and panel 3 for considerations regarding selection of medical therapy.<br>§Lifelong monitoring for hypopituitarism and secondary neoplasia in the radiation field required.<br>¶On maximum tolerated dose of the drug.]]

Most cases of Cushingoid symptoms are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions.  Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms.{{citation needed|date=August 2020}}

If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic [[pituitary adenoma]] should be removed after diagnosis. Regardless of the adenoma's location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with [[hydrocortisone]] or [[prednisolone]] is imperative.{{citation needed|date=August 2020}}

In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. [[ketoconazole]], [[metyrapone]]) but they are of limited efficacy.{{Citation needed|date=July 2013}} [[Mifepristone]] is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostasis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushing's syndrome.<ref>{{cite journal | vauthors = Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF | title = Rapid reversal of psychotic depression using mifepristone | journal = Journal of Clinical Psychopharmacology | volume = 21 | issue = 5 | pages = 516–521 | date = October 2001 | pmid = 11593077 | doi = 10.1097/00004714-200110000-00009 | s2cid = 3067889 }}</ref> However, the medication faces considerable controversy due to its use as an [[abortifacient]]. In February 2012, the FDA approved mifepristone to control high blood sugar levels ([[hyperglycemia]]) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women—although pregnancy is extremely rare during the course of Cushing's Syndrome.<ref>{{cite journal | vauthors = Parksook WW, Porntharukchareon T, Sunthornyothin S | title = Desmopressin Stimulation Test in a Pregnant Patient with Cushing's Disease | journal = AACE Clinical Case Reports | volume = 8 | issue = 3 | pages = 105–108 | date = 2022-05-30 | pmid = 35602876 | pmc = 9123553 | doi = 10.1016/j.aace.2021.11.005 }}</ref><ref>{{cite journal | vauthors = Caimari F, Valassi E, Garbayo P, Steffensen C, Santos A, Corcoy R, Webb SM | title = Cushing's syndrome and pregnancy outcomes: a systematic review of published cases | journal = Endocrine | volume = 55 | issue = 2 | pages = 555–563 | date = February 2017 | pmid = 27704478 | doi = 10.1007/s12020-016-1117-0 | s2cid = 19349163 }}</ref><ref>{{cite journal | vauthors = Lindsay JR, Jonklaas J, Oldfield EH, Nieman LK | title = Cushing's syndrome during pregnancy: personal experience and review of the literature | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 5 | pages = 3077–3083 | date = May 2005 | pmid = 15705919 | doi = 10.1210/jc.2004-2361 | s2cid = 37344210 | doi-access = free }}</ref><ref>{{cite web |url=http://www.salutedomani.com/il_weblog_di_antonio/2012/02/fda-approves-mifepristone-korlym-for-patients-with-endogenous-cushing-s-syndrome.html |title=FDA approves mifepristone (Korlym*) for patients with endogenous Cushing' s syndrome |date=February 18, 2012 |url-status=dead |archive-url=https://archive.today/20120909132942/http://www.salutedomani.com/il_weblog_di_antonio/2012/02/fda-approves-mifepristone-korlym-for-patients-with-endogenous-cushing-s-syndrome.html |archive-date=September 9, 2012 }}</ref> In March 2020, Isturisa ([[osilodrostat]]) oral tablets a 11-beta-hydroxylase enzyme inhibitor was approved by FDA for treating those patients who cannot undergo pituitary surgery or for patients who underwent surgery but continue to have the disease.<ref>{{Cite web | author = Office of the Commissioner|date=2020-03-24|title=FDA Approves New Treatment for Adults with Cushing's Disease|url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-cushings-disease|access-date=2020-06-21|website=FDA|language=en}}</ref>

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol.<ref>{{cite journal | vauthors = Aggarwal S, Yadav K, Sharma AP, Sethi V | title = Laparoscopic bilateral transperitoneal adrenalectomy for Cushing syndrome: surgical challenges and lessons learnt | journal = Surgical Laparoscopy, Endoscopy & Percutaneous Techniques | volume = 23 | issue = 3 | pages = 324–328 | date = June 2013 | pmid = 23752002 | doi = 10.1097/SLE.0b013e318290126d | s2cid = 34513590 }}</ref> In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as [[Nelson's syndrome]].<ref name="pmid14426442">{{cite journal | vauthors = Nelson DH, Meakin JW, Thorn GW | title = ACTH-producing pituitary tumors following adrenalectomy for Cushing's syndrome | journal = Annals of Internal Medicine | volume = 52 | issue = 3 | pages = 560–569 | date = March 1960 | pmid = 14426442 | doi = 10.7326/0003-4819-52-3-560 }}</ref>

==Epidemiology==
Cushing's syndrome caused by treatment with [[corticosteroid]]s is the most common form. Cushing's disease is rare; a Danish study found an incidence of less than one case per million people per year.<ref name="pmid11231987">{{cite journal | vauthors = Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jørgensen J, Kosteljanetz M, Kristensen L, Laurberg P, Schmidt K, Weeke J | display-authors = 6 | title = Incidence and late prognosis of cushing's syndrome: a population-based study | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 1 | pages = 117–123 | date = January 2001 | pmid = 11231987 | doi = 10.1210/jcem.86.1.7093 | doi-access = free }}</ref> However, asymptomatic microadenomas (less than 10&nbsp;mm in size) of the pituitary are found in about one in six individuals.<ref name="pmid15274075">{{cite journal | vauthors = Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE | title = The prevalence of pituitary adenomas: a systematic review | journal = Cancer | volume = 101 | issue = 3 | pages = 613–619 | date = August 2004 | pmid = 15274075 | doi = 10.1002/cncr.20412 | s2cid = 16595581 | author-link3 = William Couldwell | doi-access = free }}</ref>

About 0.9 to 1% of those with Cushing's syndrome have a tendency to develop [[venous thrombosis]]. Other factors such as surgery and obesity also increase the chance of getting thrombosis.<ref name="pmid19454584">{{cite journal | vauthors = Van Zaane B, Nur E, Squizzato A, Dekkers OM, Twickler MT, Fliers E, Gerdes VE, Büller HR, Brandjes DP | display-authors = 6 | title = Hypercoagulable state in Cushing's syndrome: a systematic review | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 94 | issue = 8 | pages = 2743–2750 | date = August 2009 | pmid = 19454584 | doi = 10.1210/jc.2009-0290 }}</ref>

==Persons known with Cushing's==
In February 2024, [[Amy Schumer]] announced that she had been diagnosed with Cushing's syndrome.<ref>{{cite news|url=https://www.bbc.com/news/entertainment-arts-68401132|title=Amy Schumer: Actress reveals she has Cushing's Syndrome|publisher=BBC News|first=Helen|last=Bushby|date=February 26, 2024|access-date=February 27, 2024}}</ref>

[[Jeongyeon]] from [[Korean Wave|Korean]] [[girl group]] [[Twice]] has been diagnosed with Cushing's Syndrome after taking steroid drugs for a [[Disc herniation|herniated disc]] in her neck in 2020.<ref>{{Cite web |last=기자 |first=최지혜 |date=2024-07-25 |title=Twice Jeongyeon's Sudden Weight Gain: Caused by Steroids? |url=https://kormedi.com/1708289/#:~:text=Cushing's%20syndrome%20which%20Jeongyeon%20experienced,endocrine%20system,%20produce%20various%20hormones. |access-date=2025-03-03 |website=코메디닷컴 |language=ko-KR}}</ref>

== See also ==
* [[Addison's disease]]
* [[Adrenal insufficiency]] (hypocortisolism)
* [[Corticosteroid-induced lipodystrophy]]
* [[Pituitary pars intermedia dysfunction]]
{{Clear}}

== References ==
{{Reflist}}

== External links ==
* {{cite web | url = https://medlineplus.gov/cushingssyndrome.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Cushing's Syndrome }}

{{Medical condition classification and resources
 | DiseasesDB     =
 | ICD11          = {{ICD11|5A70}}
 | ICD10          = {{ICD10|E|24||e|20}}
 | ICD9           = {{ICD9|255.0}}
 | ICDO           =
 | OMIM           =
 | MedlinePlus    = 000410
 | eMedicineSubj  = article
 | eMedicineTopic = 117365
 | MeshID         = D003480
}}
{{Adrenal gland disorder}}
{{Paraneoplastic syndromes}}
{{Authority control}}

{{DEFAULTSORT:Cushing's Syndrome}}
[[Category:Adrenal gland disorders]]
[[Category:Medical conditions related to obesity]]
[[Category:Syndromes affecting the endocrine system]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Wikipedia medicine articles ready to translate]]