Editing Cushing's syndrome (section)

==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"/>