$Unique_ID{BRK03639} $Pretitle{} $Title{Cushing Syndrome} $Subject{Cushing Syndrome Cushing's Disease Ectopic ACTH Syndrome Adrenal Neoplasm Adrenal hyperfunction pituitary ACTH excess Addison's Disease} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1989, 1991, 1992 National Organization for Rare Disorders, Inc. 126: Cushing Syndrome ** IMPORTANT ** It is possible that the main title of the article (Cushing's Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Cushing's Disease Ectopic ACTH Syndrome Adrenal Neoplasm Adrenal hyperfunction resulting from pituitary ACTH excess Information on the following diseases can be found in the Related Disorders section of this report: Addison's Disease General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Cushing's Syndrome consists of a group of Symptoms caused by an excess of cortisol and certain other hormones produced by the adrenal gland. The disorder usually occurs as a result of hormone secreting tumors in either the adrenal gland or the pituitary gland. Sometimes hormone secreting tumors may develop in other organs. Cushing's Syndrome occurs more frequently in females than in males, particularly women in their thirties following a pregnancy. The prognosis is good if the tumors can be removed. For patients who are not suitable candidates for surgery, drug therapy suppresses adrenal corticosteroid production. Symptoms The most common symptom shown by Cushing's Syndrome patients is excessive weight gain resulting in a rounding of the face and an obese torso with fat deposited particularly in the neck and above the collar bone. The arms and legs tend to remain slender. A reddened face with thin skin and visible blood vessels is also characteristic of Cushing's Syndrome. Wounds tend to heal poorly and bruises appear easily. Bluish-red stretch marks resulting from weakened connective tissue appear over the abdomen, thighs, buttocks, arms, armpits and breasts. Women with Cushing's Syndrome commonly develop excessive hair growth (hirsutism) on the face, neck, chest, abdomen and thighs. Menstrual disorders are also common with irregular or absent periods. Men with Cushing's Syndrome often experience decreased fertility along with a diminished or absent sex drive. High blood pressure, resulting from a buildup of fat in the arteries (atherosclerosis), occurs in 85% of patients with Cushing's Syndrome. Bones often become brittle and easily break or crack due to a decrease in bone mass (osteoporosis). High blood sugar (hyperglycemia), psychiatric disturbances, severe weakness and fatigue are also characteristic of this disorder. Causes Cushing's Syndrome results from an excess secretion of the hormone cortisol. Elevated levels of cortisol are most commonly the result of benign tumors of the pituitary gland. These pituitary tumors secrete the hormone ACTH (adrenocorticotropin) which, in turn, signals the adrenal glands to overproduce cortisol. This form of the syndrome is referred to as Cushing's Disease. Nonmalignant tumors in the adrenal glands are another cause of excess cortisol secretion. Potentially malignant tumors that arise in different parts of the body may also be responsible for an increase in ACTH. Cushing's Syndrome resulting from these tumors is called ectopic ACTH syndrome. The most common form of this type of tumor is oat cell or small cell lung cancer. Elevated levels of cortisol can also be caused by the long-term use of such hormones as prednisone which is used for the treatment of inflammatory illnesses such as rheumatoid arthritis. Prednisone should not be taken on a long-term basis if this is medically possible, in order to avoid this side effect. Elevated levels of cortisol may be caused in rare cases by the abnormal response of the adrenal glands to the ingestion of food. Food intake causes the release of protein-like substances from the stomach (gastric inhibitory polypeptides (or GIPs) that normally stimulate the adrenal glands to secrete cortisol. In some people with Cushing's Syndrome, the adrenal glands may secrete an abnormally excessive amount of cortisol in response to these protein-like substances. It is not understood why the adrenal glands respond abnormally in these cases of Cushing's Syndrome. Affected Population Cushing's Syndrome affects more women than men in a ratio of five to one. The age of onset is most commonly between 30 and 40 years, and women who have just given birth are at higher risk. Cushing's Disease makes up about 70% of all reported cases; Ectopic ACTH syndrome is responsible for about 17% of all reported cases. Adrenal tumors are responsible for the remainder of the reported cases. Related Disorders Symptoms of the following disorders can be similar to those of Cushing's Syndrome. Comparisons may be useful for a differential diagnosis: Addison's Disease is characterized by an underproduction of adrenocortical hormones, particularly aldosterone, a hormone that regulates salt and water balance and blood pressure. (For more information on this disorder, choose "Addison" as your search term in the Rare Disease Database). Therapies: Standard Treatment of Cushing's Syndrome relates directly to the cause of the cortisol overproduction. Pituitary tumors may be removed surgically in an operation known as a transsphenoidal adenomectomy. Procedures and results vary according to the location and type of tumor. The success rate of this procedure is over 80%. After surgery, there is an expected drop in the production of ACTH. To compensate for this temporary deficit of ACTH, patients are given a synthetic hormone called hydrocortisone. This therapy usually lasts for less than one year. Patients who have not had success with surgery, or who are not suitable candidates for surgery, may be treated with radiotherapy. The pituitary gland is treated by radiation for a period of six weeks. Improvement occurs in 40% to 50% of adult patients and in approximately 80% of children. The drug Mitotane is often used in combination with the radiation therapy to help speed recovery. Occasionally, Mitotane is used alone. Other drugs used to control the production of excess cortisol are aminoglutethimide, metyrapone and ketoconazole. To stop the overproduction of cortisol caused by ectopic ACTH syndrome, all of the cancerous tissue that is secreting ACTH must by destroyed. Cancer treatment depends upon the type of cancer present and the extent to which it has spread. Cancer treatments may include surgery, radiotherapy, chemotherapy, immunotherapy or combinations of any of these. A cortisol- inhibiting drug such as mitotane is an important part of this treatment. Adrenal tumors are most commonly removed by surgery. If the cause of the elevated level of cortisol is due to the long-term use of hormones such as prednisone for the treatment of another disorder, the dosage may be reduced until symptoms are under control. The orphan drug trilostane (Modrastane) has been approved by the FDA for treatment of Cushing's Syndrome. Therapies: Investigational Researchers are studying a glucocorticoid antagonist, RU 486, for treatment of Cushing's Syndrome. The use of this drug is currently limited to clinical trials, and more research is needed to determine long-term safety and effectiveness. This research is going on at the National Institutes of Child Health and Human Development. Scientists are currently studying patients with Cushing's Syndrome at the National Institutes of Health (NIH) in Bethesda, Maryland. Physicians who are interested in referring a patient with Cushing's syndrome may contact: Dr. George P. Chrousos Developmental Endocrinology Branch NICHD Building 10, Room 10N262 Bethesda, Maryland 20892 (301) 496-4686 Scientists are in the process of developing new and better testing methods for diagnosing Cushing's Syndrome. The test under investigation involves the sampling of the drainage from the pituitary gland. Catheterization of the bilateral femoral vein allows sampling of the petrosal sinus. Then after administration of CRH, a definite diagnosis can be made of Cushing's Syndrome. Clinical trials are underway to study the CRH stimulation test in the evaluation of patients with Cushing's Syndrome. Interested persons may wish to contact: Dr. Karen Elkind-Hirsch, Ph.D. The Methodist Hospital, Dept. of Medicine-MS b200 6565 Fanin St. Houston, TX 77030 (713) 793-1088 to see if further patients are needed for this research. Clinical trials are underway to study the diagnosis and treatment of Cushing's Syndrome. Interested persons may wish to contact: Dr. David N. Orth AA-4206 Medical Center North Vanderbilt University Nashville, TN 37232 (615) 322-6199 to see if further patients are needed for this research. Clinical trials are underway for the hormonal evaluation of patients with Cushing Syndrome. Interested persons may wish to contact: Roy E. Weiss, M.D., Ph.D. Thyroid Study Unit, Box 138, University of Chicago 5841 South Maryland Ave. Chicago, Il 60637 (312) 702-6939 to see if further patients are needed for this study. This disease entry is based upon medical information available through October 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Cushing's Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Cushing Syndrome Association 4645 Van Nuys Blvd., #104. Sherman Oaks, CA 91403 (818) 788-9239 The National Adrenal Diseases Foundation 505 Northern Blvd., Suite 200 Great Neck, NY 11021 (516) 487-4992 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Brain and Pituitary Foundation of America 1360 Ninth Ave., Suite 210 San Francisco, CA 94122 (209) 227-5466 References THE MERCK MANUAL, Volume 1, 14th Ed.: Robert Berkow, M.D. ed.-in-chief; Merck Sharp & Dohme Laboratories., 1982. Pp. 680. INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. Pp. 1947-51. GASTRIC INHIBITORY POLYPEPTIDE-DEPENDENT CORTISOL HYPERSECRETION - A NEW CASE HISTORY. Andre LaCroix, et al., NE Jour Med (October 1992 327(14)): Pp. 974-980. FOOD-DEPENDENT CUSHING'S SYNDROME MEDIATED BY ABERRANT ADRENAL SENSITIVITY TO GASTRIC INHIBITORY POLYPEPTIDE. Y. Reznik, et al., NE Jour Med (October 1992 327 (14)): Pp. 981-986.