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Cushing Syndrome

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What is Cushing syndrome?

Cushing syndrome is a group of signs and symptoms caused by abnormally high levels of cortisol (hypercortisolism). Cortisol is produced by the outer layer of the adrenal glands, called the cortex. Cortisol is a steroid hormone that breaks down fat and protein and stimulates liver glucose production. It helps the body react to physical and emotional stress, helps to regulate blood pressure, to control inflammation, and can affect cardiovascular function. The adrenal glands are located at the top of each kidney and are part of the endocrine system, a network of glands that produce hormones. The adrenal cortex produces the steroid hormones cortisol, aldosterone and the adrenal androgens, primarily dehydroepiandrosterone (DHEA).

Feedback system between hypothalamus, pituitary and adrenal glandsProduction of cortisol is controlled through a feedback system in the endocrine system involving the adrenal glands, the pituitary gland, and the hypothalamus, a gland in the lower part of the brain. When the cortisol level is low, the hypothalamus produces corticotropin-releasing hormone (CRH). This stimulates the pituitary gland, located below it, to produce adrenocorticotropic hormone (ACTH), also called corticotropin, which then stimulates the adrenal glands to produce and release cortisol. When the cortisol level is high, production of CRH and ACTH decrease.

Common causes of this relatively rare condition are:

  • Prolonged glucocorticoid therapy (iatrogenic Cushing syndrome) -- a result of taking glucocorticoids-steroid hormones that are chemically similar to natural cortisol, such as anti-inflammatory medications like prednisone prescribed for asthma, rheumatoid arthritis, lupus, and other inflammatory diseases. Such hormones may also be taken after an organ transplant to suppress the immune system and prevent organ rejection.
  • Cushing disease -- caused by a pituitary gland that produces too much of the hormone ACTH, which then signals the adrenal glands to produce cortisol. Cushing disease, a form of Cushing syndrome, occurs in about 40% of cases and is the most common cause of excess endogenous cortisol production by the adrenal glands. It is caused by a pituitary tumor (adenoma) that secretes ACTH.
  • An adrenal gland tumor or adrenal hyperplasia can cause the adrenal gland to overproduce cortisol.
  • A tumor in another part of the body such as the pancreas, lung, or thyroid can produce ACTH (called "ectopic" ACTH production because it is produced somewhere other than the pituitary gland).

Cushing syndrome can affect anyone, but it is most frequently seen in adults between the ages of 20 to 50 years and is 3 times more common in women than men. It is estimated that there are two new cases per million people each year. Rarely, a person may have an inherited gene mutation, such as Multiple Endocrine Neoplasia Type 1 or MEN-1, which increases the risk of developing tumors throughout the endocrine system, including pituitary and adrenal tumors. People who are obese and have type 2 diabetes along with poorly controlled blood glucose are at increased risk for Cushing syndrome.

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