Cushing's syndrome: Difference between revisions

Latest revision as of 19:53, 5 November 2025

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Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol.^[1]^[2]^[3] Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora,^[4] a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly.^[5]^[6] Women may have more hair and irregular menstruation or loss of menses, with the exact mechanisms of why still unknown.^[7]^[6] Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.^[6]

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 glands.^[8] 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.^[1] A number of other tumors, often referred to as ectopic due to their placement outside the pituitary, may also cause Cushing's.^[1]^[9] Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex.^[10] Diagnosis requires a number of steps.^[11] The first step is to check the medications a person takes.^[11] The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone.^[11] If this test is abnormal, the cortisol may be measured late at night.^[11] If the cortisol remains high, a blood test for ACTH may be done.^[11]

Most cases can be treated and cured.^[12] If brought on by medications, these can often be slowly decreased if still required or slowly stopped.^[13]^[14] If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation.^[13] If the pituitary was affected, other medications may be required to replace its lost function.^[13] With treatment, life expectancy is usually normal.^[12] Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.^[15]

About two to three cases per million persons are caused overtly by a tumor.^[10] It most commonly affects people who are 20 to 50 years of age.^[1] Women are affected three times more often than men.^[10] A mild degree of overproduction of cortisol without obvious symptoms, however, is more common.^[16] Cushing's syndrome was first described by American neurosurgeon Harvey Cushing in 1932.^[17] Cushing's syndrome may also occur in other animals including cats, dogs, and horses.^[18]^[19]

Signs and symptoms

File:Cushing syndrome svg hariadhi.svg

Symptoms of Cushing's syndrome^[20]

File:CushingsBody.jpg

Increased hair and stria in a 30-year-old female patient with iatrogenic Cushing's syndrome^[21]

File:BabyCushing.png

Features of Cushing syndrome including a round face, acne, reddish skin, central obesity, and poor muscle tone^[22]

Symptoms include rapid 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 collarbone, on the back of the neck ("buffalo hump" or lipodystrophy), and on the face ("moon face"). Other symptoms include excess sweating, dilation of capillaries, thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red 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.^[23]

Many of the features of Cushing's are those seen in metabolic syndrome, including insulin resistance, hypertension, obesity, and elevated blood levels of triglycerides.^[24]

Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol,^[25] and may be early indicators of exogenous or endogenous Cushing's. Depression and anxiety disorders are also common.^[26]

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.^[27]Template:Rp

Other signs include increased urination (and accompanying increased thirst), persistent 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 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 tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased 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 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.Script error: No such module "Unsubst".

Brain changes such as cerebral atrophy may occur.^[28] This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and correlates highly with psychopathological personality changes.^[29]^[30]^[31]^[32]

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 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.^[33]

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.^[33]

Causes

Cushing's syndrome may result from any cause of increased glucocorticoid levels, whether due to medication or internal processes.^[3]^[34] 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.^[35]^[34]^[36]

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.^[37] 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.^[38]^[39]

Exogenous

The most common cause of Cushing's syndrome is the use of prescribed glucocorticoids to treat other diseases (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.^[40]^[41] 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.^[35]^[42]

Cushing's syndrome in childhood is especially rare; it usually results from use of glucocorticoid medication.^[43]

Endogenous

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 glands.^[44]

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.^[45]
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 paraneoplastic Cushing's disease and is seen in diseases such as small cell lung cancer.^[46]
Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.^[47]

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 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.^[48]

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.Script error: No such module "Unsubst".

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.Script error: No such module "Unsubst".

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.Script error: No such module "Unsubst".

When Cushing's syndrome is due to extra ACTH it is known as ectopic Cushing syndrome.^[49] 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.^[50] 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 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.Script error: No such module "Unsubst".

When any of these tests is positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (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 (petrosal sinus sampling) is necessary. In many cases, the tumors causing Cushing's disease are less than 2 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.^[51]

Plasma CRH levels are inadequate at diagnosis (with the possible exception of tumors secreting CRH) because of peripheral dilution and binding to CRHBP.^[52]

Diagnosis

File:Diagnostic algorithm of suspected Cushing's syndrome.png

Diagnostic algorithm of suspected Cushing's syndrome:^[53]
ACTH=adrenocorticotropic hormone.
CBG=corticosteroid-binding globulin.
CRH=corticotropin-releasing hormone.
DST=dexamethasone suppression test.
IPSS=inferior petrosal sinus sampling.
UFC=urinary free cortisol.
*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.
†This alternative option does not have clear consensus and needs further research, and this is indicated by darker boxes.
Green boxes indicate points to consider
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.^[54]

Hypercortisolism is related with routine chemistry abnormalities such as neutrophilic leucocytosis, hyperglycemia, hypokalaemia, hypercholesterolemia, and hypercoagulability.^[55]

Urinary cortisol levels directly reflect circulating free cortisol.^[54] Excess cortisol saturates binding proteins and is eliminated in urine as free cortisol, making it a helpful diagnostic for hypercortisolemia.^[56] Values four times higher than the top range of normal are uncommon, especially in Cushing's disease.^[57] A single measurement lacks sensitivity for people with intermittent hypercortisolemia.^[58]

Treatment

File:Management algorithm of Cushing's disease.png

Management algorithm of Cushing's disease:^[53]
DST=dexamethasone suppression test.
IPSS=inferior petrosal sinus sampling.
ACTH=adrenocorticotropic hormone.
*Pituitary surgery should be performed by an experienced surgeon.
†Absence of ACTH-staining adenoma.
‡See table 2 and panel 3 for considerations regarding selection of medical therapy.
§Lifelong monitoring for hypopituitarism and secondary neoplasia in the radiation field required.
¶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.Script error: No such module "Unsubst".

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.Script error: No such module "Unsubst".

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.Script error: No such module "Unsubst". 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.^[59] 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.^[60]^[61]^[62]^[63] 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.^[64]

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol.^[65] 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.^[66]

For cushoid animals, the condition can be treated with the medication Pergolide.

Epidemiology

Cushing's syndrome caused by treatment with corticosteroids 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.^[67] However, asymptomatic microadenomas (less than 10 mm in size) of the pituitary are found in about one in six individuals.^[68]

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.^[69]

Persons with Cushing's

In February 2024, Amy Schumer announced that she had been diagnosed with Cushing's syndrome.^[70]

Jeongyeon from Korean girl group Twice has been diagnosed with Cushing's Syndrome after taking steroid drugs for a herniated disc in her neck in 2020.^[71]

References

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External links

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↑ 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,
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↑ Le Tissier, P.R; Hodson, D.J; Lafont C; Fontanaud P; Schaeffer, M; Mollard, P. (2012) Anterior pituitary cell networks. Front Neuroendocrinol. Aug; 33(3):252-66
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[37] 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,

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@@ Line 6: / Line 6: @@
 | 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>
+| 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 | page = 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/>
@@ Line 25: / Line 25: @@
 <!-- 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>
+'''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|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=978-0-7817-5443-9|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=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/symptoms|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/>
+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=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/causes|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=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/diagnosis|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>
+Most cases can be treated and cured.<ref name="NIH2012Tx">{{cite web|title=Is there a cure for Cushing's syndrome?|url=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/cure|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=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/treatments|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>
+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|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=https://www.nichd.nih.gov/health/topics/cushing/conditioninfo|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=978-0-323-24074-1|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>]]
+[[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 | article-number = 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>
@@ Line 74: / Line 74: @@
 |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"/>
+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 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=https://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>
+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 | page = 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}}
+[[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.<ref>Le Tissier, P.R; Hodson, D.J; Lafont C; Fontanaud P; Schaeffer, M; Mollard, P. (2012) Anterior pituitary cell networks. Front Neuroendocrinol. Aug; 33(3):252-66</ref>
 * 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>
@@ Line 95: / Line 95: @@
 ===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>
+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 | page = 769 | date = October 1992 | pmid = 1436049 | pmc = 1436049 | doi = 10.1136/jcp.s1-3.1.11 | bibcode = 1992Natur.359..769K }}</ref>
 ==Pathophysiology==
@@ Line 113: / Line 113: @@
 ==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
+[[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.]]
@@ Line 123: / Line 123: @@
 ==Treatment==
-[[File:Management algorithm of Cushing's disease.png|thumb|left|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.]]
+[[File:Management algorithm of Cushing's disease.png|thumb|left|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}}
@@ Line 129: / Line 129: @@
 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}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref>
+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 |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}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</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>
+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 | url = https://archive.org/details/sim_annals-of-internal-medicine_1960-03_52_3/page/560 | 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>
+For cushoid animals, the condition can be treated with the medication Pergolide.
 ==Epidemiology==
@@ Line 138: / Line 140: @@
 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==
+==Persons 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>
@@ Line 176: / Line 178: @@
 [[Category:Medical conditions related to obesity]]
 [[Category:Syndromes affecting the endocrine system]]
+[[Category:Syndromes with craniofacial abnormalities]]
 [[Category:Wikipedia emergency medicine articles ready to translate]]
 [[Category:Wikipedia medicine articles ready to translate]]

Cushing's syndrome: Difference between revisions

Latest revision as of 19:53, 5 November 2025

Contents

Signs and symptoms

Hyperpigmentation

Causes

Exogenous

Endogenous

Pseudo-Cushing's syndrome

Pathophysiology

Diagnosis

Treatment

Epidemiology

Persons with Cushing's

See also

References

External links

Navigation menu

Cushing's syndrome: Difference between revisions

Latest revision as of 19:53, 5 November 2025

Signs and symptoms

Hyperpigmentation

Causes

Exogenous

Endogenous

Pseudo-Cushing's syndrome

Pathophysiology

Diagnosis

Treatment

Epidemiology

Persons with Cushing's

See also

References

External links

Navigation menu

Search