Cushing's syndrome

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Cushing's syndrome
Classifications and external resources
Cortisol
ICD-10 E24.
ICD-9 255.0
DiseasesDB 3242
MedlinePlus 000410
eMedicine med/485 

Cushing's syndrome or hypercortisolism or hyperadrenocorticism is an endocrine disorder caused by excessive levels of the endogenous corticosteroid hormone cortisol. It may also be induced iatrogenically by treatment with exogenous corticosteroids for other medical conditions. It was discovered by American physician, surgeon and endocrinologist Harvey Cushing (1869-1939) and reported by him in 1932.

Cushing's syndrome is also a relatively common condition in domestic dogs in which causes are the same as the syndrome in humans.

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[edit] Signs and symptoms

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), "moon face", excess sweating, telangiectasia (dilation of capillaries), atrophy of the skin (which gets thin and bruises easily) and other mucous membranes, purple or red striae 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 buffalo hump). The excess cortisol may also affect other endocrine systems and cause, for example, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to frank psychosis. Depression and anxiety, including panic attacks, are common.

Other signs include persistent hypertension (due to the aldosterone-like effects) and insulin resistance, leading to hyperglycemia (high blood sugars) which can lead to diabetes mellitus. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation of the skin, due to its ability to stimulate melanocyte receptors.

[edit] Diagnosis

When Cushing's is suspected, a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH levels) and 24-hour urinary measurement for cortisol have equal detection rates (Raff & Findling 2003). 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 hormones may need to be determined, and performing physical examination directed for any visual field defect may be necessary if a pituitary lesion is suspected (which may compress the optic chiasm causing typical bitemporal hemianopia).

When these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed. These should be performed when other tests are positive, to decrease likelihood of incidentalomas (incidental discovery of harmless lesions in both organs). 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.

[edit] Pathophysiology

Cortisol is secreted by the adrenal glands under regulation by the pituitary gland and hypothalamus. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. Cushing's disease refers only to hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a pituitary gland adenoma.

[edit] Treatment

If an adrenal adenoma is identified it may be removed by surgery. Pituitary ACTH producing 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.

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.

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 (Nelson et al 1960).

In iatrogenic Cushing's, dose adjustment may be sufficient or it may be necessary to change to another type of immunosuppresive medication.

[edit] Epidemiology

Iatrogenic Cushing's syndrome (caused by treatment with corticosteroids) is the most common form of Cushing's syndrome. Endogenous (i.e. non-iatrogenic) Cushing's syndrome is relatively rare.

Incidence of causes of Cushing's syndrome per million person-years:

  • Cushing's disease: 10
  • Primary adrenal: 3
  • Ectopic ACTH: 1.4

[edit] Hyperadrenocorticism in Companion Animals

Hyperadrenalcorticism is an important disease in domestic dogs and domestic ferrets. Most cases in both species are caused by hyperplasia of the adrenal cortex in response to pituitary dysfunction. Hyperadrenalcorticism in pet animals is usually treated with long term drug therapy. In dogs, treatment is accomplished with trilostane or with mitotane. Dogs with pituitary-dependent Cushing's syndrome may be treated by radiation therapy directed against a pituitary adenoma. Dogs productive adrenal tumors may be treated by adrenalectomy.

[edit] See also


[edit] References

  • Cushing HW. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp 1932;50:137-195.
  • Nelson DH, Meakin JW, Thorn GW. ACTH-producing tumors following adrenalectomy for Cushing's syndrome. Ann Intern Med 1960;52:560–569. PMID 14426442.
  • Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med 2003;138:980-91. PMID 12809455.

[edit] External links


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