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Cushing's Syndrome

Cushing's syndrome

Definition

Cushing's syndrome is a relatively rare endocrine (hormonal) disorder resulting from excessive exposure to the hormone cortisol. The disorder, which leads to a variety of symptoms and physical abnormalities, is most commonly caused by taking medications containing the hormone over a long period of time. A more rare form of the disorder occurs when the body itself produces an excessive amount of cortisol.

Description

The adrenals are two glands, each of which is perched on the upper part of the two kidneys. The outer part of the gland is known as the cortex; the inner part is known as the medulla. Each of these parts of the adrenal gland is responsible for producing different types of hormones. Regulation of hormone production and release from the adrenal cortex involves the pituitary gland, a small gland located at the base of the brain. After the hypothalamus (the part of the brain containing secretions important to metabolic activities) sends "releasing hormones" to the pituitary gland, the pituitary secretes a hormone called adrenocorticotropic hormone (ACTH). The ACTH then travels through the bloodstream to the adrenal cortex, where it encourages the production and release of cortisol (sometimes called the "stress" hormone) and other adrenocortical hormones.

Cortisol, a very potent glucocorticoida group of adrenocortical hormones that protects the body from stress and affect protein and carbohydrate metabolism is involved in regulating the functioning of nearly every type of organ and tissue in the body, and is considered to be one of the few hormones absolutely necessary for life. Cortisol is involved in:

  • complex processing and utilization of many nutrients, including sugars (carbohydrates), fats, and proteins
  • normal functioning of the circulatory system and the heart
  • functioning of muscles
  • normal kidney function
  • production of blood cells
  • normal processes involved in maintaining the skeletal system
  • proper functioning of the brain and nerves
  • normal responses of the immune system

Cushing's syndrome, also called hypercortisolism, has an adverse effect on all of the processes described above. The syndrome occurs in approximately 10 to 15 out of every one million people per year, usually striking adults between the ages of 20 and 50.

Causes and symptoms

The most common cause of Cushing's syndrome is the long-term use of glucocorticoid hormones in medications. Medications such as prednisone are used in a number of inflammatory conditions. Such conditions include rheumatoid arthritis, asthma, vasculitis, lupus, and a variety of other autoimmune disorders in which the body's immune cells accidentally attack some part of the body itself. In these disorders, the glucocorticoids are used to dampen the immune response , thereby decreasing damage to the body.

Cushing's syndrome can also be caused by three different categories of disease:

  • a pituitary tumor producing abnormally large quantities of ACTH
  • the abnormal production of ACTH by some source other than the pituitary
  • a tumor within the adrenal gland overproducing cortisol

Although it is rare, about two-thirds of endogenous (occurring within the body rather than from a source outside the body, like a medication) Cushing's syndrome is a result of Cushing's disease. The term "Cushing's disease" refers to Cushing's syndrome, which is caused by excessive secretion of ACTH by a pituitary tumor, usually an adenoma (noncancerous tumor). The pituitary tumor causes increased growth of the adrenal cortex (hyperplasia) and increased cortisol production. Cushing's disease affects women more often than men.

Tumors in locations other than the pituitary can also produce ACTH. This is called ectopic ACTH syndrome ("ectopic" refers to something existing out of its normal place). Tumors in the lung account for more than half of all cases of ectopic ACTH syndrome. Other types of tumors which may produce ACTH include tumors of the thymus, the pancreas, the thyroid, and the adrenal gland. In each case, the secreting part of the tumor may be in the primary tumor, part of the primary tumor, or may be a small, difficult-to-find, metastatic lesion (s). Nearly all adrenal gland tumors are benign (noncancerous), although in rare instances a tumor may actually be cancerous.

Symptoms of cortisol excess (resulting from medication or from the body's excess production of the hormone) include:

  • weight gain
  • an abnormal accumulation of fatty pads in the face (creating the distinctive "moon face" of Cushing's syndrome); in the trunk (termed "truncal obesity"); and over the upper back and the back of the neck (giving the individual what has been called a "buffalo hump")
  • purple and pink stretch marks across the abdomen and flanks
  • high blood pressure
  • weak, thinning bones (osteoporosis)
  • weak muscles
  • low energy
  • thin, fragile skin, with a tendency toward both bruising and slow healing
  • abnormalities in the processing of sugars (glucose), with occasional development of actual diabetes
  • kidney stones
  • increased risk of infections
  • emotional disturbances, including mood swings, depression , irritability, confusion, or even a complete break with reality (psychosis)
  • irregular menstrual periods in women
  • decreased sex drive in men and difficulty maintaining an erection
  • abormal hair growth in women (in a male pattern, such as in the beard and mustache area), as well as loss of hair from the head (receding hair line).

Diagnosis

Diagnosing Cushing's syndrome can be complex. Diagnosis must not only identify the cortisol excess but also locate its source. Many of the symptoms listed above can be attributed to numerous other diseases. Although a number of these symptoms seen together would certainly suggest Cushing's syndrome, the symptoms are still not specific to Cushing's syndrome. Following a review of the patient's medical history, physical examination, and routine blood tests, a series of more sophisticated tests is available to achieve a diagnosis.

24-hour free cortisol test

This is the most specific diagnostic test for identifying Cushing's syndrome. It involves measuring the amount of cortisol present in the urine over a 24-hour period. When excess cortisol is present in the bloodstream, it is processed by the kidneys and removed as waste in the urine. This 24-hour free cortisol test requires that an individual collect exactly 24-hours' worth of urine in a single container. The urine is then analyzed in a laboratory to determine the quantity of cortisol present. This technique can also be paired with the administration of dexamethasone , which in a normal individual would cause urine cortisol to be very low. Once a diagnosis has been made using the 24-hour free cortisol test, other tests are used to find the exact location of the abnormality causing excess cortisol production.

Dexamethasone suppression test

This test is useful in distinguishing individuals with excess ACTH production due to a pituitary adenoma from those with ectopic ACTH-producing tumors. Patients are given dexamethasone (a synthetic glucocorticoid) orally every six hours for four days. Low doses of dexamethasone are given during the first two days; for the last two days, higher doses are administered. Before dexamethasone is administered, as well as on each day of the test, 24-hour urine collections are obtained.

Because cortisol and other glucocorticoids signal the pituitary to decrease ACTH, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Thus, the cortisol response to dexamethasone differs depending on whether the cause of Cushing's syndrome is a pituitary adenoma or an ectopic ACTH-producing tumor.

However, the dexamethasone suppression test may produce false-positive results in patients with conditions such as depression, alcohol abuse, high estrogen levels, acute illness, and stress. On the other hand, drugs such as phenytoin and phenobarbital may produce false-negative results. Thus, patients are usually advised to stop taking these drugs at least one week prior to the test.

Corticotropin-releasing hormone (CRH) stimulation test

The CRH stimulation test is given to help distinguish between patients with pituitary adenomas and those with either ectopic ACTH syndrome or cortisol-secreting adrenal tumors . In this test, patients are given an injection of CRH, the corticotropin-releasing hormone that causes the pituitary to secrete ACTH. In patients with pituitary adenomas, blood levels of ACTH and cortisol usually rise. However, in patients with ectopic ACTH syndrome, this rise is rarely seen. In patients with cortisol-secreting adrenal tumors, this rise almost never occurs.

Petrosal sinus sampling

Although this test is not always necessary, it may be used to distinguish between a pituitary adenoma and an ectopic source of ACTH. Petrosal sinus sampling involves drawing blood directly from veins that drain the pituitary. This test, which is usually performed with local anesthesia and mild sedation, requires inserting tiny, flexible tubes (catheters) through a vein in the upper thigh or groin area. The catheters are then threaded up slowly until they reach veins in an area of the skull known as the petrosal sinuses. X rays are typically used to confirm the correct position of the catheters. Often CRH is also given during the test to increase the accuracy of results.

When blood tested from the petrosal sinuses reveals a higher ACTH level than blood drawn from a vein in the forearm, the likely diagnosis is a pituitary adenoma. When the two samples show similar levels of ACTH, the diagnosis indicates ectopic ACTH syndrome.

Radiologic imaging tests

Imaging tests such as computed tomography scans (CT) and magnetic resonance imaging (MRI) are only used to look at the pituitary and adrenal glands after a firm diagnosis has already been made. The presence of a pituitary or adrenal tumor does not necessarily guarantee that it is the source of increased ACTH production. Many healthy people with no symptoms or disease whatsoever have noncancerous tumors in the pituitary and adrenal glands. Thus, CT and MRI is often used to image the pituitary and adrenal glands in preparation for surgery.

Treatment

The choice of a specific treatment depends on the type of problem causing the cortisol excess. Pituitary and adrenal adenomas are usually removed surgically. Malignant adrenal tumors always require surgical removal.

Treatment of ectopic ACTH syndrome also involves removing all of the cancerous cells which are producing ACTH. This may be done through surgery, chemotherapy (using combinations of cancer-killing drugs), or radiation therapy (using x rays to kill cancer cells), depending on the type of cancer and how far it has spread. Radiation therapy may also be used on the pituitary (with or without surgery), for patients who cannot undergo surgery, or for patients whose surgery did not successfully decrease pituitary release of ACTH.

There are a number of drugs that are effective in decreasing adrenal production of cortisol. These medications include mitotane , ketoconazole, metyrapone, trilostane, aminoglutethimide , and mifepristone. These drugs are sometimes given prior to surgery in an effort to reverse the problems brought on by cortisol excess. However, the drugs may also need to be administered after surgery (sometimes along with radiation treatments) in patients who continue to have excess pituitary production of ACTH.

Because pituitary surgery can cause ACTH levels to drop too low, some patients require short-term treatment with a cortisol-like medication after surgery. Patients who need adrenal surgery may also require glucocorticoid replacement. If the entire adrenal gland has been removed, the patient must take oral glucocorticoids for the rest of his or her life.

Prognosis

Prognosis depends on the source of the problem. When pituitary adenomas are identified as the source of increased ACTH leading to cortisol excess, about 80% of patients are cured by surgery. When cortisol excess is due to some other form of cancer, the prognosis depends on the type of cancer and the extent of its spread.

Resources

BOOKS

Brickner, Colleen. Inside Out: An Autobiography. Spokane, WA: A.H. Clark Co., 1992.

DeGroot, Leslie J., ed., et al. "Cushing's syndrome." InEndocrinology, Vol. 2. Philadelphia: W.B. Saunders Co., 1995, 1741-69.

Williams, Gordon H., and Robert G. Dluhy. "Hyperfunction of the Adrenal Cortex." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

PERIODICALS

Boscaro, Marco, Luisa Barzon, Francesco Fallo, and Nicoletta Sonino. "Cushing's Syndrome." Lancet 357 (2001): 783-91.

Boscaro, Marco, Luisa Barzon, and Nicoletta Sonino. "The Diagnosis of Cushing's Syndrome: Atypical Presentations and Laboratory Shortcomings." Archives of Internal Medicine 160 (2000): 3045-53.

Findlay, C.A., J.F. Macdonald, A.M. Wallace, N. Geddes, and M.D.C. Donaldson. "Childhood Cushing's Syndrome Induced by Betamethasone Nose Drops, and Repeat Prescriptions." British Medical Journal 3, no.17 (12 September, 1998): 739-40.

Kirk, Lawrence F., Robert B. Hash, Harold P. Katner, and Tom Jones. "Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation." American Family Physician 62, no.5 (1 September, 2001): 1119-27.

Newell-Price J., and A. Grossman. "Diagnosis and Management of Cushing's Syndrome." Lancet 353 (1999): 2087-88.

Orth, David N. "Cushing's Syndrome." The New England Journal of Medicine 332, no. 12 (23 March, 1995): 791-803.

Utiger, Robert D. "Treatment, and Retreatment, of Cushing'sDisease." The New England Journal of Medicine 336, no.3 (16 January, 1997): 215-17.

ORGANIZATION

Cushing's Support and Research Foundation, Inc. 65 East India Row, Suite 22B, Boston, MA 02110. (617) 723-3674. <http://www.world.std.com>.

National Adrenal Disease Foundation. 505 Northern Boulevard, Suite 200, Great Neck, NY 11021. (516) 487-4992. <http://www.medhelp.org>.

National Institute of Neurological Disorders and Stroke (NINDS). National Institutes of Health, Bethesda, MD 20892-2560. <http://www.ninds.nih.gov>.

Pituitary Network Association. 16350 Ventura Boulevard, #231, Encino, CA 91436. (805)499-9973. <http://www.pituitary.org>.

Rosalyn Carson-DeWitt, M.D.

KEY TERMS

Adenoma

A type of noncancerous (benign) tumor that often involves the overgrowth of certain cells of the type normally found within glands.

Adrenocorticotropic hormone (ACTH)

A pituitary hormone that stimulates the cortex of the adrenal glands to produce adrenal cortical hormones.

Cortisol

A hormone secreted by the cortex of the adrenal gland. Cortisol regulates the function of nearly every organ and tissue in the body.

Ectopic

In an abnormal position.

Endocrine

Pertaining to a gland that secretes directly into the bloodstream.

Gland

A collection of cells whose function is to release certain chemicals (hormones) that are important to the functioning of other, sometimes distantly located, organs or body systems.

Glucocorticoids

General class of adrenal cortical hormones that are mainly active in protecting against stress and in protein and carbohydrate metabolism.

Hormone

A chemical produced in one part of the body, which travels to another part of the body in order to exert its effect.

Hypothalamus

the part of the brain containing secretions important to metabolic activities.

Pituitary

A gland located at the base of the brain, the pituitary produces a number of hormones, including hormones which regulate growth and reproductive function.

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Cushing's Syndrome

Cushing's Syndrome

Definition

Cushing's syndrome is a relatively rare endocrine (hormonal) disorder resulting from excessive exposure to the hormone cortisol. The disorder, which leads to a variety of symptoms and physical abnormalities, is most commonly caused by taking medications containing the hormone over a long period of time. A more rare form of the disorder occurs when the body itself produces an excessive amount of cortisol.

Description

The adrenals are two glands, each of which is perched on the upper part of the two kidneys. The outer part of the gland is known as the cortex; the inner part is known as the medulla. Each of these parts of the adrenal gland is responsible for producing different types of hormones. Regulation of hormone production and release from the adrenal cortex involves the pituitary gland, a small gland located at the base of the brain. After the hypothalamus (the part of the brain containing secretions important to metabolic activities) sends "releasing hormones" to the pituitary gland, the pituitary secretes a hormone called adrenocorticotropic hormone (ACTH). The ACTH then travels through the bloodstream to the adrenal cortex, where it encourages the production and release of cortisol (sometimes called the "stress" hormone) and other adrenocortical hormones.

Cortisol, a very potent glucocorticoida group of adrenocortical hormones that protects the body from stress and affect protein and carbohydrate metabolismis involved in regulating the functioning of nearly every type of organ and tissue in the body, and is considered to be one of the few hormones absolutely necessary for life. Cortisol is involved in:

  • complex processing and utilization of many nutrients, including sugars (carbohydrates), fats, and proteins
  • normal functioning of the circulatory system and the heart
  • functioning of muscles
  • normal kidney function
  • production of blood cells
  • normal processes involved in maintaining the skeletal system
  • proper functioning of the brain and nerves
  • normal responses of the immune system

Cushing's syndrome, also called hypercortisolism, has an adverse effect on all of the processes described above. The syndrome occurs in approximately 10 to 15 out of every one million people per year, usually striking adults between the ages of 20 and 50.

Causes and symptoms

The most common cause of Cushing's syndrome is the long-term use of glucocorticoid hormones in medications. Medications such as prednisone are used in a number of inflammatory conditions. Such conditions include rheumatoid arthritis, asthma, vasculitis, lupus, and a variety of other autoimmune disorders in which the body's immune cells accidentally attack some part of the body itself. In these disorders, the glucocorticoids are used to dampen the immune response, thereby decreasing damage to the body.

Cushing's syndrome can also be caused by three different categories of disease:

  • a pituitary tumor producing abnormally large quantities of ACTH
  • the abnormal production of ACTH by some source other than the pituitary
  • a tumor within the adrenal gland overproducing cortisol

Although it is rare, about two-thirds of endogenous (occurring within the body rather than from a source outside the body, like a medication) Cushing's syndrome which is caused by excessive secretion of ACTH by a pituitary tumor, usually an adenoma (noncancerous tumor). The pituitary tumor causes increased growth of the adrenal cortex (hyperplasia) and increased cortisol production. Cushing's disease affects women more often than men.

Tumors in locations other than the pituitary can also produce ACTH. This is called ectopic ACTH syndrome ("ectopic" refers to something existing out of its normal place). Tumors in the lung account for more than half of all cases of ectopic ACTH syndrome. Other types of tumors that may produce ACTH include tumors of the thymus, the pancreas, the thyroid, and the adrenal gland. Nearly all adrenal gland tumors are benign (noncancerous), although in rare instances a tumor may actually be cancerous.

Symptoms of cortisol excess (resulting from medication or from the body's excess production of the hormone) include:

  • weight gain
  • an abnormal accumulation of fatty pads in the face (creating the distinctive "moon face" of Cushing's syndrome); in the trunk (termed "truncal obesity"); and over the upper back and the back of the neck (giving the individual what has been called a "buffalo hump")
  • purple and pink stretch marks across the abdomen and flanks
  • high blood pressure
  • weak, thinning bones (osteoporosis)
  • weak muscles
  • low energy
  • thin, fragile skin, with a tendency toward both bruising and slow healing
  • abnormalities in the processing of sugars (glucose), with occasional development of actual diabetes
  • kidney stones
  • increased risk of infections
  • emotional disturbances, including mood swings, depression, irritability, confusion, or even a complete break with reality (psychosis)
  • irregular menstrual periods in women
  • decreased sex drive in men and difficulty maintaining an erection
  • abormal hair growth in women (in a male pattern, such as in the beard and mustache area), as well as loss of hair from the head (receding hair line).

Diagnosis

Diagnosing Cushing's syndrome can be complex. Diagnosis must not only identify the cortisol excess, but also locate its source. Many of the symptoms listed above can be attributed to numerous other diseases. Although a number of these symptoms seen together would certainly suggest Cushing's syndrome, the symptoms are still not specific to Cushing's syndrome. Following a review of the patient's medical history, physical examination, and routine blood tests, a series of more sophisticated tests is available to achieve a diagnosis.

24-hour free cortisol test

This is the most specific diagnostic test for identifying Cushing's syndrome. It involves measuring the amount of cortisol present in the urine over a 24-hour period. When excess cortisol is present in the bloodstream, it is processed by the kidneys and removed as waste in the urine. This 24-hour free cortisol test requires that an individual collect exactly 24-hours' worth of urine in a single container. The urine is then analyzed in a laboratory to determine the quantity of cortisol present. This technique can also be paired with the administration of dexamethasone, which in a normal individual would cause urine cortisol to be very low. Once a diagnosis has been made using the 24-hour free cortisol test, other tests are used to find the exact location of the abnormality causing excess cortisol production.

Dexamethasone suppression test

This test is useful in distinguishing individuals with excess ACTH production due to a pituitary adenoma from those with ectopic ACTH-producing tumors. Patients are given dexamethasone (a synthetic glucocorticoid) orally every six hours for four days. Low doses of dexamethasone are given during the first two days; for the last two days, higher doses are administered. Before dexamethasone is administered, as well as on each day of the test, 24-hour urine collections are obtained.

Because cortisol and other glucocorticoids signal the pituitary to decrease ACTH, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Thus, the cortisol response to dexamethasone differs depending on whether the cause of Cushing's syndrome is a pituitary adenoma or an ectopic ACTH-producing tumor.

However, the dexamethasone suppression test may produce false-positive results in patients with conditions such as depression, alcohol abuse, high estrogen levels, acute illness, and stress. On the other hand, drugs such as phenytoin and phenobarbital may produce false-negative results. Thus, patients are usually advised to stop taking these drugs at least one week prior to the test.

Corticotropin-releasing hormone (CRH) stimulation test

The CRH stimulation test is given to help distinguish between patients with pituitary adenomas and those with either ectopic ACTH syndrome or cortisol-secreting adrenal tumors. In this test, patients are given an injection of CRH, the corticotropin-releasing hormone that causes the pituitary to secrete ACTH. In patients with pituitary adenomas, blood levels of ACTH and cortisol usually rise. However, in patients with ectopic ACTH syndrome, this rise is rarely seen. In patients with cortisol-secreting adrenal tumors, this rise almost never occurs.

Petrosal sinus sampling

Although this test is not always necessary, it may be used to distinguish between a pituitary adenoma and an ectopic source of ACTH. Petrosal sinus sampling involves drawing blood directly from veins that drain the pituitary. This test, which is usually performed with local anesthesia and mild sedation, requires inserting tiny, flexible tubes (catheters) through a vein in the upper thigh or groin area. The catheters are then threaded up slowly until they reach veins in an area of the skull known as the petrosal sinuses. X rays are typically used to confirm the correct position of the catheters. Often CRH is also given during the test to increase the accuracy of results.

When blood tested from the petrosal sinuses reveals a higher ACTH level than blood drawn from a vein in the forearm, the likely diagnosis is a pituitary adenoma. When the two samples show similar levels of ACTH, the diagnosis indicates ectopic ACTH syndrome.

Radiologic imaging tests

Imaging tests such as computed tomography scans (CT) and magnetic resonance imaging (MRI) are only used to look at the pituitary and adrenal glands after a firm diagnosis has already been made. The presence of a pituitary or adrenal tumor does not necessarily guarantee that it is the source of increased ACTH production. Many healthy people with no symptoms or disease whatsoever have noncancerous tumors in the pituitary and adrenal glands. Thus, CT and MRI is often used to image the pituitary and adrenal glands in preparation for surgery.

Treatment

The choice of a specific treatment depends on the type of problem causing the cortisol excess. Pituitary and adrenal adenomas are usually removed surgically. Malignant adrenal tumors always require surgical removal.

Treatment of ectopic ACTH syndrome also involves removing all of the cancerous cells that are producing ACTH. This may be done through surgery, chemotherapy (using combinations of cancer-killing drugs), or radiation therapy (using x rays to kill cancer cells), depending on the type of cancer and how far it has spread. Radiation therapy may also be used on the pituitary (with or without surgery) for patients who cannot undergo surgery, or for patients whose surgery did not successfully decrease pituitary release of ACTH.

There are a number of drugs that are effective in decreasing adrenal production of cortisol. These medications include mitotane, ketoconazole, metyrapone, trilostane, aminoglutethimide, and mifepristone. These drugs are sometimes given prior to surgery in an effort to reverse the problems brought on by cortisol excess. However, the drugs may also need to be administered after surgery (sometimes along with radiation treatments) in patients who continue to have excess pituitary production of ACTH.

Because pituitary surgery can cause ACTH levels to drop too low, some patients require short-term treatment with a cortisol-like medication after surgery. Patients who need adrenal surgery may also require glucocorticoid replacement. If the entire adrenal gland has been removed, the patient must take oral glucocorticoids for the rest of his or her life.

Prognosis

Prognosis depends on the source of the problem. When pituitary adenomas are identified as the source of increased ACTH leading to cortisol excess, about 80% of patients are cured by surgery. When cortisol excess is due to some other form of cancer, the prognosis depends on the type of cancer and the extent of its spread.

KEY TERMS

Adenoma A type of noncancerous (benign) tumor that often involves the overgrowth of certain cells of the type normally found within glands.

Adrenocorticotropic hormone (ACTH) A pituitary hormone that stimulates the cortex of the adrenal glands to produce adrenal cortical hormones.

Cortisol A hormone secreted by the cortex of the adrenal gland. Cortisol regulates the function of nearly every organ and tissue in the body.

Ectopic In an abnormal position.

Endocrine Pertaining to a gland that secretes directly into the bloodstream.

Gland A collection of cells whose function is to release certain chemicals (hormones) that are important to the functioning of other, sometimes distantly located, organs or body systems.

Glucocorticoids General class of adrenal cortical hormones that are mainly active in protecting against stress and in protein and carbohydrate metabolism.

Hormone A chemical produced in one part of the body that travels to another part of the body in order to exert its effect.

Hypothalamus the part of the brain containing secretions important to metabolic activities.

Pituitary A gland located at the base of the brain, the pituitary produces a number of hormones, including hormones that regulate growth and reproductive function.

Resources

BOOKS

Williams, Gordon H., and Robert G. Dluhy. "Hyperfunction of the Adrenal Cortex." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

PERIODICALS

Boscaro, Marco, Luisa Barzon, and Nicoletta Sonino. "The Diagnosis of Cushing's Syndrome: Atypical Presentations and Laboratory Shortcomings." Archives of Internal Medicine 160 (2000): 3045-53.

Boscaro, Marco, Luisa Barzon, Francesco Fallo, and Nicoletta Sonino. "Cushing's Syndrome." Lancet 357 (2001): 783-91.

Kirk, Lawrence F., Robert B. Hash, Harold P. Katner, and Tom Jones. "Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation." American Family Physician 62, no. 5 (September 1, 2001): 1119-27.

Newell-Price J., and A. Grossman. "Diagnosis and Management of Cushing's Syndrome." Lancet 353 (1999): 2087-88.

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Carson-DeWitt, Rosalyn. "Cushing's Syndrome." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Encyclopedia.com. 28 Jun. 2016 <http://www.encyclopedia.com>.

Carson-DeWitt, Rosalyn. "Cushing's Syndrome." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Encyclopedia.com. (June 28, 2016). http://www.encyclopedia.com/doc/1G2-3451600468.html

Carson-DeWitt, Rosalyn. "Cushing's Syndrome." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Retrieved June 28, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3451600468.html

Cushing's syndrome

Cushing's syndrome (kuush-ingz) n. the condition resulting from excess amounts of corticosteroid hormones in the body. Symptoms include weight gain, reddening of the face and neck, excess growth of body and facial hair, raised blood pressure, loss of mineral from the bones (osteoporosis), raised blood glucose levels, and sometimes mental disturbances. The syndrome may be due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumour of the pituitary gland (Cushing's disease) or by a malignant tumour in the lung or elsewhere. [ H. W. Cushing (1869–1939), US surgeon]

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"Cushing's syndrome." A Dictionary of Nursing. 2008. Encyclopedia.com. 28 Jun. 2016 <http://www.encyclopedia.com>.

"Cushing's syndrome." A Dictionary of Nursing. 2008. Encyclopedia.com. (June 28, 2016). http://www.encyclopedia.com/doc/1O62-Cushingssyndrome.html

"Cushing's syndrome." A Dictionary of Nursing. 2008. Retrieved June 28, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O62-Cushingssyndrome.html

Cushing’s Syndrome

Cushings Syndrome

What Is Cushings Syndrome?

What Are the Signs and Symptoms of Cushings Syndrome?

How Is Cushings Syndrome Diagnosed and Treated?

Resources

Cushings syndrome is a condition that occurs when the body is exposed to high levels of the hormone Cortisol. Symptoms may include muscle weakness, extra body fat, excess hair, and emotional problems.

KEYWORDS

for searching the Internet and other reference sources

Adrenocorticotropin (ACTH)

Corticotropin-releasing hormone (CRH)

Cortisol

Endocrine system

Hormones

What Is Cushings Syndrome?

Cushings syndrome is an endocrine, or hormone*, condition. It occurs when the body is exposed to high levels of the hormone Cortisol for long periods of time.

* hormones
are chemicals that are produced by different glands in the body. Hormones are like the bodys ambassadors: they are created in one place but are sent through the body to have specific regulatory effects in different places.

Cortisol and the endocrine system

Cortisol is a hormone essential for life. It is involved in maintaining blood pressure and the immune system and in the bodys handling of proteins, carbohydrates, and fats. It also helps the body respond to stress. However, too much Cortisol has negative effects on the body.

Usually, Cortisol production is tightly regulated by the interactions of three parts of the endocrine system:

  1. A part of the brain called the hypothalamus (hy-po-THAL-mus) secretes corticotropin-releasing hormone (CRH).
  2. CRH signals gland attached to the brain, the pituitary gland, to release adrenocorticotropin (ACTH).
  3. ACTH signals the adrenal glands to make Cortisol and release it into the bloodstream. The adrenal glands are a pair of organs located just above the kidneys in the abdominal cavity.

If something goes wrong with any of these glands or with the signaling system, the body may produce too much Cortisol.

Tumors

Certain tumors, either cancerous or noncancerous, can cause Cushings syndrome. For example, noncancerous pituitary tumors that secrete ACTH are a cause of the condition. Tumors elsewhere in the body, such as in the lungs, also can produce ACTH, and tumors of the adrenal glands can cause overproduction of Cortisol. Most cases of Cushings syndrome are not inherited, but the tendency to develop tumors can be inherited.

Cortisone-based therapies

Treatment with high doses of cortisone-based hormone medications for asthma, rheumatoid arthritis, lupus, and other inflammatory diseases is the most common reason people develop Cushings syndrome.

What Are the Signs and Symptoms of Cushings Syndrome?

In 1932, the American neurosurgeon Harvey Williams Cushing (1869 1939) described eight patients with symptoms of what later was named Cushings syndrome. Dr. Cushing described how too much Cortisol led to:

  • obesity, especially of the face, neck, and upper body
  • purplish stretch marks associated with weight gain
  • thin and fragile skin that bruises easily
  • slow wound healing
  • weakened bones (osteoporosis)
  • fatigue and weak muscles
  • problems with sugar metabolism, which may lead to diabetes
  • menstrual irregularities
  • growth of excess hair
  • high blood pressure
  • irritability and depression.

How Is Cushings Syndrome Diagnosed and Treated?

Diagnosis

A doctor who sees a patient with symptoms suggestive of Cushings syndrome will ask questions about the persons medical history and perform a physical exam. Laboratory tests, such as analysis of blood and urine, are used to measure Cortisol levels. If Cortisol levels are high, other tests are done to find out why. For example, imaging techniques for looking inside the body (such as CT scans* and MRIs*) can be used to look for tumors.

* CT scans
or CAT scans are the shortened names for computerized axial tomography, which uses computers to view cross sections inside the body.
* MRI
means magnetic resonance imaging, which uses magnets to view inside the body.

Treatment

Treatment of tumors varies depending on the type. A tumor may be removed surgically, or it may be treated with radiation or chemotherapy. Sometimes Cushings syndrome is treated with drugs to inhibit Cortisol production. If Cushings syndrome occurs as a side effect of hormone therapy, doctors can alter the dosage to minimize the side effects of the medication.

Altering hormone dosage and removal of tumors can lead to a full recovery, although sometimes the tumors come back. Because Cushings syndrome can be difficult to diagnose, affected people sometimes live with the condition for years before it is diagnosed and treated.

See also

Hypertension

Metabolic Disease

Obesity

Osteoporosis

Resources

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) posts a fact sheet about Cushings syndrome at its website.

http://www.niddk.nih.gov/health/endo/pubs/cushings/cushings.htm

Cushings Support and Research Foundation, Inc., 65 East India Row 22B, Boston, MA 02110.

Telephone 617-723-3824
http://world.std.com/~csrf/

Pituitary Tumor Network Association, 16350 Ventura Boulevard,
Number 231, Encino, CA 91436.
Telephone 805-499-9973
http://www.pituitary.com

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