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$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
     [phone]

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
     [phone]

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
     [phone]

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
     [phone]

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
     [phone]

     National Cushing Syndrome Association
     4645 Van Nuys Blvd., #104.
     Sherman Oaks, CA 91403
     [phone]

     The National Adrenal Diseases Foundation
     505 Northern Blvd., Suite 200
     Great Neck, NY  11021
     [phone]

     National Digestive Diseases Information Clearinghouse
     Box NDDIC
     Bethesda, MD  20892
     [phone]

     Brain and Pituitary Foundation of America
     1360 Ninth Ave., Suite 210
     San Francisco, CA 94122
     [phone]

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.