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Cushing's Syndrome Cushing’s Syndrome National Endocrine and Metabolic Diseases Information Service What is Cushing’s Women with Cushing’s syndrome usually have excess hair growth on their face, neck, syndrome? chest, abdomen, and thighs. Their menstrual Cushing’s syndrome is a hormonal periods may become irregular or stop. Men U.S. Department disorder caused by prolonged exposure may have decreased fertility with diminished of Health and of the body’s tissues to high levels of the or absent desire for sex and, sometimes, Human Services hormone cortisol. Sometimes called erectile dysfunction. hypercortisolism, Cushing’s syndrome is NATIONAL Other common signs and symptoms include INSTITUTES relatively rare and most commonly affects OF HEALTH adults aged 20 to 50. People who are obese • severe fatigue and have type 2 diabetes, along with poorly controlled blood glucose—also called blood • weak muscles sugar—and high blood pressure, have an • high blood pressure increased risk of developing the disorder. • high blood glucose What are the signs and • increased thirst and urination symptoms of Cushing’s • irritability, anxiety, or depression syndrome? • a fatty hump between the shoulders Signs and symptoms of Cushing’s syndrome Sometimes other conditions have many of vary, but most people with the disorder the same signs as Cushing’s syndrome, even have upper body obesity, a rounded face, though people with these disorders do not increased fat around the neck, and relatively have abnormally elevated cortisol levels. slender arms and legs. Children tend to be For example, polycystic ovary syndrome can obese with slowed growth rates. cause menstrual disturbances, weight gain beginning in adolescence, excess hair growth, Other signs appear in the skin, which and impaired insulin action and diabetes. becomes fragile and thin, bruises easily, Metabolic syndrome—a combination of and heals poorly. Purple or pink stretch problems that includes excess weight around marks may appear on the abdomen, thighs, the waist, high blood pressure, abnormal buttocks, arms, and breasts. The bones are levels of cholesterol and triglycerides in the weakened, and routine activities such as blood, and insulin resistance—also mimics bending, lifting, or rising from a chair may the symptoms of Cushing’s syndrome. lead to backaches and rib or spinal column fractures. What causes Cushing’s syndrome? Pituitary Hypothalamus gland Cushing’s syndrome occurs when the CRH body’s tissues are exposed to high levels of ACTH cortisol for too long. Many people develop Cushing’s syndrome because they take glucocorticoids—steroid hormones that are Adrenal chemically similar to naturally produced glands cortisol—such as prednisone for asthma, rheumatoid arthritis, lupus, and other Cortisol inflammatory diseases. Glucocorticoids are also used to suppress the immune system after transplantation to keep the body from rejecting the new organ or tissue. Other people develop Cushing’s syndrome because their bodies produce too much cortisol. Normally, the production of The hypothalamus sends CRH to the pituitary, which responds by secreting ACTH. ACTH then causes the cortisol follows a precise chain of events. adrenals to release cortisol into the bloodstream. First, the hypothalamus, a part of the brain about the size of a small sugar cube, sends corticotropin-releasing hormone (CRH) One of cortisol’s most important jobs is to the pituitary gland. CRH causes the to help the body respond to stress. For pituitary to secrete adrenocorticotropin this reason, women in their last 3 months hormone (ACTH), which stimulates the of pregnancy and highly trained athletes adrenal glands. When the adrenals, which normally have high levels of the hormone. are located just above the kidneys, receive People suffering from depression, the ACTH, they respond by releasing cortisol alcoholism, malnutrition, or panic disorders into the bloodstream. also have increased cortisol levels. Cortisol performs vital tasks in the body When the amount of cortisol in the blood is including adequate, the hypothalamus and pituitary release less CRH and ACTH. This process • helping maintain blood pressure and ensures the amount of cortisol released by cardiovascular function the adrenal glands is precisely balanced to • reducing the immune system’s meet the body’s daily needs. However, if inflammatory response something goes wrong with the adrenals or the regulating switches in the pituitary gland • balancing the effects of insulin, which or hypothalamus, cortisol production can breaks down glucose for energy go awry. • regulating the metabolism of proteins, carbohydrates, and fats 2 Cushing’s Syndrome Pituitary Adenomas Adrenal Tumors Pituitary adenomas cause 70 percent of In rare cases, an abnormality of the adrenal Cushing’s syndrome cases,1 excluding those glands, most often an adrenal tumor, causes caused by glucocorticoid use. These benign, Cushing’s syndrome. Adrenal tumors are or noncancerous, tumors of the pituitary four to five times more common in women gland secrete extra ACTH. Most people than men, and the average age of onset with the disorder have a single adenoma. is about 40. Most of these cases involve This form of the syndrome, known as noncancerous tumors of adrenal tissue called Cushing’s disease, affects women five times adrenal adenomas, which release excess more often than men. cortisol into the blood. Ectopic ACTH Syndrome Adrenocortical carcinomas—adrenal cancers—are the least common cause of Some benign or, more often, cancerous Cushing’s syndrome. With adrenocortical tumors that arise outside the pituitary can carcinomas, cancer cells secrete excess produce ACTH. This condition is known levels of several adrenocortical hormones, as ectopic ACTH syndrome. Lung tumors including cortisol and adrenal androgens, cause more than half of these cases, and men a type of male hormone. Adrenocortical are affected three times more often than carcinomas usually cause very high hormone women. The most common forms of ACTH- levels and rapid development of symptoms. producing tumors are small cell lung cancer, which accounts for about 13 percent of all Familial Cushing’s Syndrome lung cancer cases,2 and carcinoid tumors— Most cases of Cushing’s syndrome are not small, slow-growing tumors that arise from inherited. Rarely, however, Cushing’s hormone-producing cells in various parts syndrome results from an inherited tendency of the body. Other less common types to develop tumors of one or more endocrine of tumors that can produce ACTH are glands. Endocrine glands release hormones thymomas, pancreatic islet cell tumors, into the bloodstream. With primary and medullary carcinomas of the thyroid. pigmented micronodular adrenal disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. With multiple endocrine neoplasia type 1 (MEN1), hormone-secreting tumors of the parathyroid glands, pancreas, and pituitary develop; Cushing’s syndrome in MEN1 may be due to pituitary, ectopic, or adrenal tumors. 1Nieman LK, Ilias I. Evaluation and treatment of Cushing’s syndrome. The Journal of American Medicine. 2005;118(12):1340–1346. 2Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. Journal of Clinical Oncology. 2006;24:4539–4544. 3 Cushing’s Syndrome How is Cushing’s However, a late-night or bedtime saliva sample can be obtained at home, then syndrome diagnosed? tested to determine the cortisol level. Diagnosis is based on a review of a person’s Diagnostic ranges vary, depending on medical history, a physical examination, the measurement technique used. and laboratory tests. X rays of the adrenal or pituitary glands can be useful in locating • Low-dose dexamethasone suppression tumors. test (LDDST). In the LDDST, a person is given a low dose of dexamethasone, a Tests to Diagnose synthetic glucocorticoid, by mouth every Cushing’s Syndrome 6 hours for 2 days. Urine is collected before dexamethasone is administered No single lab test is perfect and usually and several times on each day of the several are needed. The three most common test. A modified LDDST uses a one­ tests used to diagnose Cushing’s syndrome time overnight dose. are the 24-hour urinary free cortisol test, measurement of midnight plasma cortisol or Cortisol and other glucocorticoids signal late-night salivary cortisol, and the low-dose the pituitary to release less ACTH, dexamethasone suppression test. Another so the normal response after taking test, the dexamethasone-corticotropin­ dexamethasone is a drop in blood and releasing hormone test, may be needed urine cortisol levels. If cortisol levels to distinguish Cushing’s syndrome from do not drop, Cushing’s syndrome is other causes of excess cortisol. suspected. • 24-hour urinary free cortisol level. In The LDDST may not show a drop in this test, a person’s urine is collected cortisol levels in people with depression, several times over a 24-hour period alcoholism, high estrogen levels, acute and tested for cortisol. Levels higher illness, or stress, falsely indicating than 50 to 100 micrograms a day for an Cushing’s syndrome. On the other adult suggest Cushing’s syndrome. The hand, drugs such as phenytoin and normal upper limit varies in different phenobarbital may cause cortisol levels laboratories, depending on which to drop, falsely indicating that Cushing’s measurement technique is used. is not present in people who
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