Difference between revisions of "Cushing's syndrome" - New World Encyclopedia
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| − | '''Cushing's syndrome,''' or ''hypercortisolism,'' is an [[endocrinology|endocrine disorder]] caused by the presence of excessive levels of [[cortisol]] in the body. It is named after the American surgeon Dr. Harvey Cushing, who first described the condition in 1932. Cushing's syndrome is relatively rare and most commonly affects adults | + | '''Cushing's syndrome,''' or ''hypercortisolism,'' is an [[endocrinology|endocrine disorder]] caused by the presence of excessive levels of [[cortisol]] in the body. It is named after the American surgeon Dr. Harvey Cushing, who first described the condition in 1932. Cushing's syndrome is relatively rare and most commonly affects adults between the ages of 20 to 50 years. Approximately 10 to 15 out of every million people are affected each year by Cushing's syndrome. |
| − | Cushing's syndrome is a disorder in the regulation of [[cortisol]] or [[ACTH]] secretion, which can both lead to increased levels of [[cortisol]] in the [[blood]]. Normally, the secretion of [[cortisol]] follows a specific series of events. [[Corticotropin releasing hormone]], or [[CRH]], is released from the [[hypothalamus]], a part of the brain, to the [[pituitary gland]]. [[CRH]] causes the [[anterior pituitary]] to secrete [[ACTH]] (adrenocorticotropin), a hormone that then stimulates | + | Cushing's syndrome is a disorder in the regulation of [[cortisol]] or [[ACTH]] secretion, which can both lead to increased levels of [[cortisol]] in the [[blood]]. Normally, the secretion of [[cortisol]] follows a specific series of events. [[Corticotropin releasing hormone]], or [[CRH]], is released from the [[hypothalamus]], which is a part of the brain, to the [[pituitary gland]]. [[CRH]] causes the [[anterior pituitary]] to secrete [[ACTH]] (adrenocorticotropin), a hormone that then stimulates the [[adrenal glands]], which are located above the [[kidney]]s. When the [[adrenal glands]] receive the [[ACTH]], they respond by releasing [[cortisol]] into the bloodstream. |
| − | Cushing's syndrome has three well established causes. First, adrenocortical tumors can secrete [[cortisol]] autonomously in the absence of [[ACTH]]. Such tumors can be either cancerous or non- cancerous (benign). This cause of Cushing's syndrome is described as ''primary hypersecretion''. Second, some benign or malignant | + | Cushing's syndrome has three well established causes. First, adrenocortical tumors can secrete [[cortisol]] autonomously in the absence of [[ACTH]]. Such tumors can be either cancerous (malignant) or non- cancerous (benign). This cause of Cushing's syndrome is described as ''primary hypersecretion''. Second, some benign or malignant tumors that arise outside the [[anterior pituitary]] can produce [[ACTH]]. This condition is known as ''ectopic [[ACTH]] syndrome''. Lung tumors cause over 50 percent of these such cases. Men are affected three times more frequently than women. Third, [[anterior pituitary]] malfunctions can cause increased [[ACTH]] secretion, which in turn stimulate secretion of [[cortisol]] by the [[adrenal glands]]. This condition is referred to specifically as ''Cushing's disease'' and is called ''secondary hypersecretion''. It affects women five times more frequently than men. |
| − | A common iatrogenic cause of Cushing's syndrome is exogenous administration of corticosteroids to treat various other medical conditions such as inflammation and rheumatoid arthiritis. Family hereditary can also play a part in the onset of the syndrome, although it is quite rare. Some individuals have | + | A common iatrogenic cause of Cushing's syndrome is exogenous administration of corticosteroids to treat various other medical conditions such as inflammation and rheumatoid arthiritis. Family hereditary can also play a part in the onset of the syndrome, although it is quite rare. Some individuals have peculiar causes of Cushing's syndrome due to an inherited disposition to develop tumors of one or more endocrine glands. In ''primary pigmented micronodular adrenal disease'', children or young adults develop small [[cortisol]]-producing tumors of the [[adrenal glands]]. In ''multiple endocrine neoplasia type I (MEN I)'', hormone secreting tumors of the [[parathyroid glands]], [[pancreas]] and [[anterior pituitary]] occur. Cushing's syndrome in ''MEN I'' may be due to [[anterior pituitary]], ectopic and/or adrenal tumors. |
==Signs and Symptoms== | ==Signs and Symptoms== | ||
| − | The majority of signs of Cushing's syndrome can be predicted from the normal range of actions of [[cortisol]]. The hormone [[cortisol]] is essential for life and serves several purposes in the human body. Its main function is to maintain blood glucose levels, which it does throuh a variety of mechanisms. [[Cortisol]] promotes gluconeogenesis (glucose production) in the [[liver]], causes the breakdown of skeletal [[muscle]] proteins to provide [[amino acid]]s for gluconeogenesis, suppresses the immune system by preventing antibody production by white blood cells, causes a negative [[calcium]] balance in the body, and influences [[brain]] function by causing mood swings and changes in memory and learning abilities. | + | The majority of signs of Cushing's syndrome can be predicted from the normal range of actions of [[cortisol]]. The hormone [[cortisol]] is essential for life and serves several purposes in the human body. Its main function is to maintain blood glucose levels, which it does throuh a variety of mechanisms. [[Cortisol]] promotes gluconeogenesis (glucose production) in the [[liver]], causes the breakdown of skeletal [[muscle]] proteins to provide [[amino acid]]s for gluconeogenesis, suppresses the immune system by preventing [[antibody]] production by white blood cells, causes a negative [[calcium]] balance in the body, and influences [[brain]] function by causing mood swings and changes in memory and learning abilities. |
Patients with Cushing's syndrome experience symptoms related to increased gluconeogenesis. Tissue wasting occurs as [[muscle]] protein is broken down for glucose production mimicking diabetes. Interestingly, however, weight gain occurs due to increased appetite with extra fat deposited in the trunk and face of patients, causing the appearance of a plump "moon face." Extremeties are usually thin with central obesity and wide purplish striae, learning and memory become difficult, and an initial mood elevation is followed by depression. Excess sweating, telangiectasia (dilation of the capillaries), and hypertension also are common symptoms of the syndrome. Atropy of the skin occurs as the skin becomes thin, fragile, and easily bruised. Reaction to infections is attenuated. | Patients with Cushing's syndrome experience symptoms related to increased gluconeogenesis. Tissue wasting occurs as [[muscle]] protein is broken down for glucose production mimicking diabetes. Interestingly, however, weight gain occurs due to increased appetite with extra fat deposited in the trunk and face of patients, causing the appearance of a plump "moon face." Extremeties are usually thin with central obesity and wide purplish striae, learning and memory become difficult, and an initial mood elevation is followed by depression. Excess sweating, telangiectasia (dilation of the capillaries), and hypertension also are common symptoms of the syndrome. Atropy of the skin occurs as the skin becomes thin, fragile, and easily bruised. Reaction to infections is attenuated. | ||
| − | Common signs of Cushing's syndrome are growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump), reduced libido (or sex drive), impotence, amenorrhoea (abnormal suppression or absence of menstruation), and infertility. Patients frequently suffer various psychological disturbances as well. Other signs include persistent hypertension, or high blood pressure, due to [[aldosterone]]-like effects and [[insulin resistance]], leading to hyperglycemia (high [[blood]] sugar levels). Increased hair growth, or hirsutism, on | + | Common signs of Cushing's syndrome are growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump), reduced libido (or sex drive), impotence, amenorrhoea (abnormal suppression or absence of menstruation), and infertility. Patients frequently suffer various psychological disturbances as well. Other signs include persistent hypertension, or high blood pressure, due to [[aldosterone]]-like effects, and [[insulin resistance]], leading to hyperglycemia (high [[blood]] sugar levels). Increased hair growth, or hirsutism, on the face, abdomen, chest, and thighs of women may occur because of an excess of [[androgens]] (sex hormones). This excess hair growth may go unnoticed in men. |
Untreated Cushing's syndrome can lead to [[heart]] disease and increased mortality, or death. | Untreated Cushing's syndrome can lead to [[heart]] disease and increased mortality, or death. | ||
Revision as of 16:36, 30 May 2006
Cushing's syndrome, or hypercortisolism, is an endocrine disorder caused by the presence of excessive levels of cortisol in the body. It is named after the American surgeon Dr. Harvey Cushing, who first described the condition in 1932. Cushing's syndrome is relatively rare and most commonly affects adults between the ages of 20 to 50 years. Approximately 10 to 15 out of every million people are affected each year by Cushing's syndrome.
Cushing's syndrome is a disorder in the regulation of cortisol or ACTH secretion, which can both lead to increased levels of cortisol in the blood. Normally, the secretion of cortisol follows a specific series of events. Corticotropin releasing hormone, or CRH, is released from the hypothalamus, which is a part of the brain, to the pituitary gland. CRH causes the anterior pituitary to secrete ACTH (adrenocorticotropin), a hormone that then stimulates the adrenal glands, which are located above the kidneys. When the adrenal glands receive the ACTH, they respond by releasing cortisol into the bloodstream.
Cushing's syndrome has three well established causes. First, adrenocortical tumors can secrete cortisol autonomously in the absence of ACTH. Such tumors can be either cancerous (malignant) or non- cancerous (benign). This cause of Cushing's syndrome is described as primary hypersecretion. Second, some benign or malignant tumors that arise outside the anterior pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause over 50 percent of these such cases. Men are affected three times more frequently than women. Third, anterior pituitary malfunctions can cause increased ACTH secretion, which in turn stimulate secretion of cortisol by the adrenal glands. This condition is referred to specifically as Cushing's disease and is called secondary hypersecretion. It affects women five times more frequently than men.
A common iatrogenic cause of Cushing's syndrome is exogenous administration of corticosteroids to treat various other medical conditions such as inflammation and rheumatoid arthiritis. Family hereditary can also play a part in the onset of the syndrome, although it is quite rare. Some individuals have peculiar causes of Cushing's syndrome due to an inherited disposition to develop tumors of one or more endocrine glands. In primary pigmented micronodular adrenal disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In multiple endocrine neoplasia type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and anterior pituitary occur. Cushing's syndrome in MEN I may be due to anterior pituitary, ectopic and/or adrenal tumors.
Signs and Symptoms
The majority of signs of Cushing's syndrome can be predicted from the normal range of actions of cortisol. The hormone cortisol is essential for life and serves several purposes in the human body. Its main function is to maintain blood glucose levels, which it does throuh a variety of mechanisms. Cortisol promotes gluconeogenesis (glucose production) in the liver, causes the breakdown of skeletal muscle proteins to provide amino acids for gluconeogenesis, suppresses the immune system by preventing antibody production by white blood cells, causes a negative calcium balance in the body, and influences brain function by causing mood swings and changes in memory and learning abilities.
Patients with Cushing's syndrome experience symptoms related to increased gluconeogenesis. Tissue wasting occurs as muscle protein is broken down for glucose production mimicking diabetes. Interestingly, however, weight gain occurs due to increased appetite with extra fat deposited in the trunk and face of patients, causing the appearance of a plump "moon face." Extremeties are usually thin with central obesity and wide purplish striae, learning and memory become difficult, and an initial mood elevation is followed by depression. Excess sweating, telangiectasia (dilation of the capillaries), and hypertension also are common symptoms of the syndrome. Atropy of the skin occurs as the skin becomes thin, fragile, and easily bruised. Reaction to infections is attenuated.
Common signs of Cushing's syndrome are growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump), reduced libido (or sex drive), impotence, amenorrhoea (abnormal suppression or absence of menstruation), and infertility. Patients frequently suffer various psychological disturbances as well. Other signs include persistent hypertension, or high blood pressure, due to aldosterone-like effects, and insulin resistance, leading to hyperglycemia (high blood sugar levels). Increased hair growth, or hirsutism, on the face, abdomen, chest, and thighs of women may occur because of an excess of androgens (sex hormones). This excess hair growth may go unnoticed in men.
Untreated Cushing's syndrome can lead to heart disease and increased mortality, or death.
Diagnosis
Several tests can be employed in order to diagnose Cushing's syndrome. A 24-Hour Urinary Free Cortisol Level test is the most specific diagnostic test available. The patient's urine is collected over a 24 hour period and periodically tested for the amount of cortisol. Levels higher than 50 to 100 micrograms a day for an adult suggest Cushing's syndrome.
The CRH Stimulation Test can be used to distinguish between patients with anterior pituitary tumors and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors. In this test, patients are given CRH. If an anterior pituitary tumor is present, a rise in blood ACTH and cortisol levels is observed. On the contrary, this response is rarely seen in patients with ectopic ACTH syndrome and essentially never seen in patients with cortisol-secreting adrenal tumors.
A third test, the Dexamethasone Suppression Test, helps to separate patients with excess ACTH production due to pituitary tumors from those with ectopic ACTH-producing tumors. Dexamethasone, a synthetic glucocorticoid, is administered to patients by mouth every 6 hours for 4 days, with an increase in dose during the last two days. Twenty-four hour urine collections are made before dexamethasone is given on each day of the test. Since cortisol and other glucocorticoids signal the anterior pituitary to lower ACTH secretion, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Differing responses of cortisol to dexamethasone result depending on whether the cause of Cushing's syndrome is a pituitary tumor or an ectopic ACTH-producing tumor. Various drugs can produce false- positive and false- negative results. Therefore, patients are often advised to stop taking these drugs at least one week prior to the test.
Radiologic imaging can be used to reveal the size and shape of the anterior pituitary and adrenal glands to determine if a tumor is present. Imaging procedures are only used to find a tumor after the diagnosis of Cushing's syndrome has been made. Often times, benign tumors are present in the pituitary and adrenal glands. However, these tumors do not produce hormones that are detrimental to the patient's health and are not surgically removed unless tests reveal they are the cause of symptoms. A computerized tomography scan, or CT scan, and magnetic resonance imaging scans, also known as MRIs, are the most common imaging tests used.
A petrosal sinus sampling test is another test used during the identification of Cushing's syndrome. Although this test is not always required, it is the best method to differentiate between pituitary and ectopic causes of Cushing's syndrome. Samples of blood are drawn from the petrosal sinuses, veins which drain the pituitary gland, and ACTH levels are compared with ACTH levels in the forearm vein. Similar levels suggest ectopic ACTH syndrome while higher levels of ACTH in the petrosal sinuses indicate the presence of a pituitary tumor.
Some individuals have high cortisol levels but do not incurr the progessive effects of Cushing's syndrome, such as muscle wasting and thinning of the skin. These individuals may have pseudo Cushing's syndrome, which does not have the same long- term effects as Cushing's syndrome. It does not require treatment directed at the endocrine glands. Although observation over months to years is necessary to differentiate between pseduo Cushing's and Cushing's syndrome, the dexamethasone-CRH test was developed to distinguish between the conditions rapidly, so that Cushing's patients can receive prompt treatment. As the name implies, this test combines the dexamethasone suppression and the CRH stimulation tests. An increase in cortisol levels during this test suggests Cushing's syndrome.
Therapy
Treatment of Cushing's syndrome depends on the specific reason for the cortisol excess present in the body.
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.
See also
ReferencesISBN links support NWE through referral fees
- 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.
External links
- Cushing's Syndrome
- Cushing's information at Oregon Health Sciences University
- Cushing's doctors
- Cushing's syndrome
- Cushing's Syndrome and Cushing's Disease
- Cushing's Syndrome mailing list
- Cushing's Disease (from Pituitary Foundation UK)
- Cushing's Syndrome/Disease in dogs
- Cushing Syndrome information at Merck.com
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