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| {{SK}} Hypercortisolism; hyperadrenocorticism | | {{SK}} Hypercortisolism; hyperadrenocorticism |
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| ==Overview== | | ==[[Cushing's syndrome overview|Overview]]== |
| '''Cushing's Syndrome''' is an [[endocrinology|endocrine disorder]] caused by high levels of [[cortisol]] in the blood from a variety of causes, including primary pituitary adenoma (known as Cushing's disease), primary adrenal hyperplasia or neoplasia, ectopic ACTH production (e.g., from a [[small cell carcinoma|small cell]] [[lung cancer]]), and iatrogenic ([[steroid]] use). Normally, cortisol is released from the [[adrenal gland]] in response to [[ACTH]] being released from the [[pituitary gland]]. Both Cushing's syndrome and Cushing's disease are characterized by elevated levels of cortisol in the blood, but the cause of elevated cortisol differs between the two. Cushing's disease specifically refers to a tumour in the [[pituitary gland]] that stimulates excessive release of cortisol from the adrenal gland by releasing large amounts of ACTH. In Cushing's disease, [[ACTH]] levels do not respond to negative feedback from the high levels of cortisol.
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| Cushing's disease was described by American [[physician]], [[surgery|surgeon]] and [[endocrinologist]] [[Harvey Cushing]] (1869-1939) and reported by him in 1932.<ref>Cushing HW. ''The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism).'' Bull Johns Hopkins Hosp 1932;50:137-195.</ref> | | ==[[Cushing's syndrome pathophysiology|Pathophysiology]]== |
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| Cushing's syndrome--which is also a relatively common condition in domestic dogs and horses--is characterised by abnormal fat deposition. | | ==[[Cushing's syndrome causes|Causes]]== |
| | [[Cushing's syndrome causes#Common causes|Common Causes]] | [[Cushing's syndrome causes#System based|System based]] | [[Cushing's syndrome causes#Alphabetical order|Alphabetical order]] |
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| == Signs and symptoms == | | ==[[Cushing's syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
| Symptoms include rapid [[obesity|weight gain]], particularly of the trunk and face with sparing of the limbs ([[central obesity]]), a round face often referred to as a "[[moon face]]", excess [[sweating]], [[telangiectasia]] (dilation of capillaries), thinning of the skin (which causes easy bruising) and other mucous membranes, purple or red [[striae]] (the weight gain in Cushing's 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). A common sign is the growth of fat pads along the collar bone and on the back of the neck (known as a [[lipodystrophy]]). The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, reduced [[libido]], [[impotence]], [[amenorrhoea]] and [[infertility]]. Patients frequently suffer various psychological disturbances, ranging from [[Euphoria (emotion)|euphoria]] to [[psychosis]]. [[clinical depression|Depression]] and [[anxiety]] are also common.<ref>{{cite book |title=The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences |last=Yudofsky |first=Stuart C. |coauthors=Robert E. Hales |edition=5th |year=2007 |publisher=American Psychiatric Pub, Inc. |isbn=1585622397 }}</ref>
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| Other signs include persistent [[hypertension]] (due to cortisol's enhancement of [[epinephrine]]'s vasoconstrictive effect) and [[insulin resistance]] (especially common in [[ectopic]] ACTH production), leading to [[hyperglycemia]] (high [[blood sugar]]s) which can lead to [[diabetes mellitus]]. Untreated Cushing's syndrome can lead to [[heart disease]] and increased [[death|mortality]]. 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 Proopiomelanocortin (POMC). Cortisol can also exhibit [[mineralcorticoid]] activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, [[gastrointestinal]] disturbances, opportunistic infections and impaired wound healing (cortisol is a stress hormone, so it depresses the immune and inflammatory responses). Osteoporosis is also problem in Cushing's Syndrome, as mentioned before, cortisol evokes a stress-like response. The body's maintenance of bone (and other tissues) is therefore no longer one of its main priorities, so to speak.
| | ==[[Cushing's syndrome risk factors|Risk Factors]]== |
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| '''Moon face''' is a medical sign where the face swells up into a rounded shape. It is often associated with [[Cushing's syndrome]], which has led to it being known as '''Cushingoid facies''' ("Cushings-like face"), or [[steroid]] treatment, which has led to the name '''steroid facies'''.
| | ==[[Cushing's syndrome natural history|Natural History, Complications and Prognosis]]== |
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| ===Exogenous Versus Endogenous===
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| There are two types of Cushing’s syndrome: exogenous and endogenous. In endogenous disease, excess cortisol production ''within'' the body is the cause, whilst in exogenous disease the causal factor is typically steroid medication (i.e. it originates ''outside'' the body) mimicing cortisol's activity. The signs and symptoms are therefore virtually identical, aside from those induced by ACTH in pituitary-dependent disease and ectopic ACTH-producing tumours (such as hyperpigmentation). The exogenous route is ''by far'' the most commonly taken in Cushing’s syndrome (a fact that all too many seem to forget). Examples of such exogenous steroid medications are those used to treat inflammatory disorders such as [[asthma]] and [[rheumatoid arthritis]], or to suppress the immune system after an organ transplant. This type of Cushing’s is temporary and goes away after the patient has finished taking the cortisol-like medications. Endogenous Cushing’s syndrome is unusual, it usually comes on slowly and can be difficult to diagnose.
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| ==Diagnosis== | | ==Diagnosis== |
| When Cushing's 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 offer equal detection rates.<ref>Raff H, Findling JW. ''A physiologic approach to diagnosis of the Cushing's syndrome.'' Ann Intern Med 2003;138:980-91. PMID 12809455</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, high cortisol would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (eg: adrenal adenoma) that 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.
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| When any of these tests are 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 [[adenoma]]s or [[incidentaloma]]s (the incidental discovery of harmless lesions). [[Scintigraphy]] of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the cortisol levels in various veins in the body by venous catheterisation, working towards the pituitary (petrosal sinus sampling) is necessary.
| | [[Cushing's syndrome history and symptoms|History and Symptoms ]] | [[ Cushing's syndrome physical examination|Physical Examination]] | [[Cushing's syndrome laboratory findings|Laboratory Findings]] | [[Cushing's syndrome CT|CT Scan]] | [[Cushing's syndrome MRI|MRI]] | [[Cushing's syndrome other diagnostic studies|Other Diagnostic Studies]] |
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| ==Pathophysiology==
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| Both the [[hypothalamus]] and the [[pituitary gland]] are in the brain. The hypothalamus releases [[corticotropin-releasing hormone]] (CRH), which stimulates the pituitary gland to release corticotropin ([[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 the pituitary, which decreases the amount of ACTH released from the pituitary gland. Strictly, '''Cushing's syndrome''' refers to excess cortisol of any etiology. One of the causes of Cushing's syndrome is a cortisol secreting adenoma in the cortex of the adrenal gland. 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. '''Cushing's disease''' refers only to hypercortisolism secondary to excess production of ACTH from a corticotrophic [[pituitary adenoma]]. This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because a tumor causes the pituitary to be unresponsive to negative feedback from high cortisol levels.
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| ==Treatment== | | ==Treatment== |
| The main point to remember is that the vast majority of cases of Cushing's syndrome are caused by steroid medications (such causes are described as [[iatrogenic]]) so healthcare workers must always remember to check patients' medications first, as stopping or reducing the dose will usually resolve the problem.
| | [[Cushing's syndrome medical therapy|Medical Therapy]] | [[Cushing's syndrome surgery |Surgery]] |
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| 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 will 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.
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| In those patients not suitable 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.
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| Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. 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>Nelson DH, Meakin JW, Thorn GW. ''ACTH-producing tumors following adrenalectomy for Cushing's syndrome.'' Ann Intern Med 1960;52:560–569. PMID 14426442</ref>
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| ==Epidemiology==
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| [[Iatrogenic]] Cushing's (caused by treatment with [[corticosteroid]]s) is the most common form of Cushing's syndrome. The incidence of pituitary tumors may be relatively high, as much as one in five people, <ref name="pmid15274075">{{cite journal |author=Ezzat S, Asa SL, Couldwell WT, ''et al'' |title=The prevalence of pituitary adenomas: a systematic review |journal=Cancer |volume=101 |issue=3 |pages=613–9 |year=2004 |pmid=15274075 |doi=10.1002/cncr.20412}}</ref> but only a minute fraction are active and produce excessive hormones.
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| ==See Also== | | ==See Also== |
| * [[Addison's disease]] | | * [[Addison's disease]] |
| * [[Pseudo-Cushing syndrome]] | | * [[Pseudo-Cushing syndrome]] |
| <!--slowly integrating this:
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| Children and teenagers get
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| * extreme weight gain
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| * growth retardation.
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| * missed periods in teenage girls
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| * excess hair growth
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| * acne
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| * reddish-blue streaks on the skin
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| * high blood pressure
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| * tiredness and weakness
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| * either very early or late puberty
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| Adults with the disease may also have symptoms of extreme weight gain, excess hair growth, high blood pressure, and skin problems. In addition, they may show:
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| * muscle and bone weakness
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| * moodiness, irritability, or depression
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| * sleep disturbances
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| * high blood sugar
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| * menstrual disorders in women and decreased fertility in men
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| Until here PD source -->
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| ==Resources== | | ==Resources== |
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| *[http://www.endocrine.niddk.nih.gov/ Endocrine and Metabolic Diseases Information Service] | | *[http://www.endocrine.niddk.nih.gov/ Endocrine and Metabolic Diseases Information Service] |
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| ==References==
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| {{reflist|2}}
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |
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| [[Category:Mature chapter]] | | [[Category:Mature chapter]] |
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| [[da:Cushings syndrom]]
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| [[de:Cushing-Syndrom]]
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| [[es:Síndrome de Cushing]]
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| [[eo:Cushing-sindromo]]
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| [[fr:Syndrome de Cushing]]
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| [[id:Sindrom Cushing]]
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| [[it:Sindrome di Cushing]]
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| [[he:תסמונת קושינג]]
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| [[ms:Sindrom Cushing]]
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| [[nl:Syndroom van Cushing]]
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| [[ja:クッシング症候群]]
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| [[no:Cushings sykdom]]
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| [[pl:Zespół Cushinga]]
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| [[pt:Síndrome de Cushing]]
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| [[sv:Cushings syndrom]]
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| [[zh:庫興氏症候群]]
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