Re: never felt so low after a Dr visit...

September 2, 2004

Introduction Cushing's syndrome is a hormonal disorder caused by

prolonged exposure of the body's tissues to high levels of the hormone

cortisol. Sometimes called " hypercortisolism, " it is relatively rare and

most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every

million people are affected each year.

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What Are the Symptoms? Symptoms vary, but most people have upper body

obesity, rounded face, increased fat around the neck, and thinning arms and

legs. Children tend to be obese with slowed growth rates.

Other symptoms appear in the skin, which becomes fragile and thin. It

bruises easily and heals poorly. Purplish pink stretch marks may appear on

the abdomen, thighs, buttocks, arms and breasts. The bones are weakened, and

routine activities such as bending, lifting or rising from a chair may lead

to backaches, rib and spinal column fractures.

Most people have severe fatigue, weak muscles, high blood pressure and

high blood sugar. Irritability, anxiety and depression are common.

Women usually have excess hair growth on their faces, necks, chests,

abdomens, and thighs. Their menstrual periods may become irregular or stop.

Men have decreased fertility with diminished or absent desire for sex.

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What Causes Cushing's Syndrome? Cushing's syndrome occurs when the

body's tissues are exposed to excessive levels of cortisol for long periods

of time. Many people suffer the symptoms of Cushing's syndrome because they

take glucocorticoid hormones such as prednisone for asthma, rheumatoid

arthritis, lupus and other inflammatory diseases, or for immunosuppression

after transplantation.

Others develop Cushing's syndrome because of overproduction of

cortisol by the body. Normally, the production of cortisol follows a precise

chain of events. First, the hypothalamus, a part of the brain which is about

the size of a small sugar cube, sends corticotropin releasing hormone (CRH)

to the pituitary gland. CRH causes the pituitary to secrete ACTH

(adrenocorticotropin), a hormone that stimulates the adrenal glands. When

the adrenals, which are located just above the kidneys, receive the ACTH,

they respond by releasing cortisol into the bloodstream.

Cortisol performs vital tasks in the body. It helps maintain blood

pressure and cardiovascular function, reduces the immune system's

inflammatory response, balances the effects of insulin in breaking down

sugar for energy, and regulates the metabolism of proteins, carbohydrates,

and fats. One of cortisol's most important jobs is to help the body respond

to stress. For this reason, women in their last 3 months of pregnancy and

highly trained athletes normally have high levels of the hormone. People

suffering from depression, alcoholism, malnutrition and panic disorders also

have increased cortisol levels.

When the amount of cortisol in the blood is adequate, the hypothalamus

and pituitary release less CRH and ACTH. This ensures that the amount of

cortisol released by the adrenal glands is precisely balanced to meet the

body's daily needs. However, if something goes wrong with the adrenals or

their regulating switches in the pituitary gland or the hypothalamus,

cortisol production can go awry.

Pituitary Adenomas

Pituitary adenomas cause most cases of Cushing's syndrome. They are

benign, or non-cancerous, tumors of the pituitary gland which secrete

increased amounts of ACTH. Most patients have a single adenoma. This form of

the syndrome, known as " Cushing's disease, " affects women five times more

frequently than men.

Ectopic ACTH Syndrome

Some benign or malignant (cancerous) tumors that arise outside the

pituitary can produce ACTH. This condition is known as ectopic ACTH

syndrome. Lung tumors cause over 50 percent of these cases. Men are affected

3 times more frequently than women. The most common forms of ACTH-producing

tumors are oat cell, or small cell lung cancer, which accounts for about 25

percent of all lung cancer cases, and carcinoid tumors. Other less common

types of tumors that can produce ACTH are thymomas, pancreatic islet cell

tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors

Sometimes, an abnormality of the adrenal glands, most often an adrenal

tumor, causes Cushing's syndrome. The average age of onset is about 40

years. Most of these cases involve non-cancerous tumors of adrenal tissue,

called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common

cause of Cushing's syndrome. Cancer cells secrete excess levels of several

adrenal cortical hormones, including cortisol and adrenal androgens.

Adrenocortical carcinomas usually cause very high hormone levels and rapid

development of symptoms.

Familial Cushing's Syndrome

Most cases of Cushing's syndrome are not inherited. Rarely, however,

some individuals have special causes of Cushing's syndrome due to an

inherited tendency 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 pituitary occur. Cushing's syndrome in MEN

I may be due to pituitary, ectopic or adrenal tumors.

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How Is Cushing's Syndrome Diagnosed? Diagnosis is based on a review of

the patient's medical history, physical examination and laboratory tests.

Often x-ray exams of the adrenal or pituitary glands are useful for locating

tumors. These tests help to determine if excess levels of cortisol are

present and why.

24-Hour Urinary Free Cortisol Level

This is the most specific diagnostic test. The patient's urine is

collected over a 24-hour period and tested for the amount of cortisol.

Levels higher than 50-100 micrograms a day for an adult suggest Cushing's

syndrome. The normal upper limit varies in different laboratories, depending

on which measurement technique is used.

Once Cushing's syndrome has been diagnosed, other tests are used to

find the exact location of the abnormality that leads to excess cortisol

production. The choice of test depends, in part, on the preference of the

endocrinologist or the center where the test is performed.

Dexamethasone Suppression Test

This test helps to distinguish patients with excess production of ACTH

due to pituitary adenomas from those with ectopic ACTH-producing tumors.

Patients are given dexamethasone, a synthetic glucocorticoid, by mouth every

6 hours for 4 days. For the first 2 days, low doses of dexamethasone are

given, and for the last 2 days, higher doses are given. Twenty-four hour

urine collections are made before dexamethasone is administered and on each

day of the test. Since cortisol and other glucocorticoids signal the

pituitary to lower secretion of ACTH, the normal response after taking

dexamethasone is a drop in blood and urine cortisol levels. Different

responses of cortisol to dexamethasone are obtained depending on whether the

cause of Cushing's syndrome is a pituitary adenoma or an ectopic

ACTH-producing tumor.

The dexamethasone suppression test can produce false-positive results

in patients with depression, alcohol abuse, high estrogen levels, acute

illness, and stress. Conversely, drugs such as phenytoin and phenobarbital

may cause false-negative results in response to dexamethasone suppression.

For this reason, patients are usually advised by their physicians to stop

taking these drugs at least one week before the test.

CRH Stimulation Test

This test helps to distinguish between patients with pituitary

adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal

tumors. Patients are given an injection of CRH, the corticotropin-releasing

hormone which causes the pituitary to secrete ACTH. Patients with pituitary

adenomas usually experience a rise in blood levels of ACTH and cortisol.

This response is rarely seen in patients with ectopic ACTH syndrome and

practically never in patients with cortisol-secreting adrenal tumors.

Direct Visualization of the Endocrine Glands (Radiologic Imaging)

Imaging tests reveal the size and shape of the pituitary and adrenal

glands and help determine if a tumor is present. The most common are the CT

(computerized tomography) scan and MRI (magnetic resonance imaging). A CT

scan produces a series of x-ray pictures giving a cross-sectional image of a

body part. MRI also produces images of the internal organs of the body but

without exposing the patient to ionizing radiation.

Imaging procedures are used to find a tumor after a diagnosis has been

established. Imaging is not used to make the diagnosis of Cushing's syndrome

because benign tumors, sometimes called " incidentalomas, " are commonly found

in the pituitary and adrenal glands. These tumors do not produce hormones

detrimental to health and are not removed unless blood tests show they are a

cause of symptoms or they are unusually large. Conversely, pituitary tumors

are not detected by imaging in almost 50 percent of patients who ultimately

require pituitary surgery for Cushing's syndrome.

Petrosal Sinus Sampling

This test is not always required, but in many cases, it is the best

way to separate pituitary from ectopic causes of Cushing's syndrome. Samples

of blood are drawn from the petrosal sinuses, veins which drain the

pituitary, by introducing catheters through a vein in the upper thigh/groin

region, with local anesthesia and mild sedation. X-rays are used to confirm

the correct position of the catheters. Often CRH, the hormone which causes

the pituitary to secrete ACTH, is given during this test to improve

diagnostic accuracy. Levels of ACTH in the petrosal sinuses are measured and

compared with ACTH levels in a forearm vein. ACTH levels higher in the

petrosal sinuses than in the forearm vein indicate the presence of a

pituitary adenoma; similar levels suggest ectopic ACTH syndrome.

The Dexamethasone-CRH Test

Some individuals have high cortisol levels, but do not develop the

progressive effects of Cushing's syndrome, such as muscle weakness,

fractures and thinning of the skin. These individuals may have Pseudo

Cushing's syndrome, which was originally described in people who were

depressed or drank excess alcohol, but is now known to be more common.

Pseudo Cushing's does not have the same long-term effects on health as

Cushing's syndrome and does not require treatment directed at the endocrine

glands. Although observation over months to years will distinguish Pseudo

Cushing's from Cushing's, the dexamethasone-CRH test was developed to

distinguish between the conditions rapidly, so that Cushing's patients can

receive prompt treatment. This test combines the dexamethasone suppression

and the CRH stimulation tests. Elevations of cortisol during this test

suggest Cushing's syndrome.

Some patients may have sustained high cortisol levels without the

effects of Cushing's syndrome. These high cortisol levels may be

compensating for the body's resistance to cortisol's effects. This rare

syndrome of cortisol resistance is a genetic condition that causes

hypertension and chronic androgen excess.

Sometimes other conditions may be associated with many of the symptoms

of Cushing's syndrome. These include polycystic ovarian syndrome, which may

cause menstrual disturbances, weight gain from adolescence, excess hair

growth and sometimes impaired insulin action and diabetes. Commonly, weight

gain, high blood pressure and abnormal levels of cholesterol and

triglycerides in the blood are associated with resistance to insulin action

and diabetes; this has been described as the " Metabolic Syndrome-X. "

Patients with these disorders do not have abnormally elevated cortisol

levels.

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How Is Cushing's Syndrome Treated? Treatment depends on the specific

reason for cortisol excess and may include surgery, radiation, chemotherapy

or the use of cortisol-inhibiting drugs. If the cause is long-term use of

glucocorticoid hormones to treat another disorder, the doctor will gradually

reduce the dosage to the lowest dose adequate for control of that disorder.

Once control is established, the daily dose of glucocorticoid hormones may

be doubled and given on alternate days to lessen side effects.

Pituitary Adenomas

Several therapies are available to treat the ACTH-secreting pituitary

adenomas of Cushing's disease. The most widely used treatment is surgical

removal of the tumor, known as transsphenoidal adenomectomy. Using a special

microscope and very fine instruments, the surgeon approaches the pituitary

gland through a nostril or an opening made below the upper lip. Because this

is an extremely delicate procedure, patients are often referred to centers

specializing in this type of surgery. The success, or cure, rate of this

procedure is over 80 percent when performed by a surgeon with extensive

experience. If surgery fails, or only produces a temporary cure, surgery can

be repeated, often with good results. After curative pituitary surgery, the

production of ACTH drops two levels below normal. This is a natural, but

temporary, drop in ACTH production, and patients are given a synthetic form

of cortisol (such as hydrocortisone or prednisone). Most patients can stop

this replacement therapy in less than a year.

For patients in whom transsphenoidal surgery has failed or who are not

suitable candidates for surgery, radiotherapy is another possible treatment.

Radiation to the pituitary gland is given over a 6-week period, with

improvement occurring in 40 to 50 percent of adults and up to 80 percent of

children. It may take several months or years before patients feel better fr

om radiation treatment alone. However, the combination of radiation and the

drug mitotane (Lysodren®) can help speed recovery. Mitotane suppresses

cortisol production and lowers plasma and urine hormone levels. Treatment

with mitotane alone can be successful in 30 to 40 percent of patients. Other

drugs used alone or in combination to control the production of excess

cortisol are aminoglutethimide, metyrapone, trilostane and ketoconazole.

Each has its own side effects that doctors consider when prescribing therapy

for individual patients.

Ectopic ACTH Syndrome

To cure the overproduction of cortisol caused by ectopic ACTH

syndrome, it is necessary to eliminate all of the cancerous tissue that is

secreting ACTH. The choice of cancer treatment--surgery, radiotherapy,

chemotherapy, immunotherapy, or a combination of these treatments--depends

on the type of cancer and how far it has spread. Since ACTH-secreting tumors

(for example, small cell lung cancer) may be very small or widespread at the

time of diagnosis, cortisol-inhibiting drugs, like mitotane, are an

important part of treatment. In some cases, if pituitary surgery is not

successful, surgical removal of the adrenal glands (bilateral adrenalectomy)

may take the place of drug therapy.

Adrenal Tumors

Surgery is the mainstay of treatment for benign as well as cancerous

tumors of the adrenal glands. In Primary Pigmented Micronodular Adrenal

Disease and the familial Carney's complex, surgical removal of the adrenal

glands is required.

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What Research Is Being Done on Cushing's Syndrome? The National

Institutes of Health (NIH) is the biomedical research component of the

Federal Government. It is one of the health agencies of the Public Health

Service, which is part of the U.S. Department of Health and Human Services.

Several components of the NIH conduct and support research on Cushing's

syndrome and other disorders of the endocrine system, including the National

Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the

National Institute of Child Health and Human Development (NICHD), the

National Institute of Neurological Disorders and Stroke (NINDS), and the

National Cancer Institute (NCI).

NIH-supported scientists are conducting intensive research into the

normal and abnormal function of the major endocrine glands and the many

hormones of the endocrine system. Identification of the corticotropin

releasing hormone (CRH), which instructs the pituitary gland to release

ACTH, enabled researchers to develop the CRH stimulation test, which is

increasingly being used to identify the cause of Cushing's syndrome.

Improved techniques for measuring ACTH permit distinction of

ACTH-dependent forms of Cushing's syndrome from adrenal tumors. NIH studies

have shown that petrosal sinus sampling is a very accurate test to diagnose

the cause of Cushing's syndrome in those who have excess ACTH production.

The recently described dexamethasone suppression-CRH test is able to

differentiate most cases of Cushing's from Pseudo Cushing's.

As a result of this research, doctors are much better able to diagnose

Cushing's syndrome and distinguish among the causes of this disorder. Since

accurate diagnosis is still a problem for some patients, new tests are under

study to further refine the diagnostic process.

Many studies are underway to understand the causes of formation of

benign endocrine tumors, such as those which cause most cases of Cushing's

syndrome. In a few pituitary adenomas, specific gene defects have been

identified and may provide important clues to understanding tumor formation.

Endocrine factors may also play a role. There is increasing evidence that

tumor formation is a multi-step process. Understanding the basis of

Cushing's syndrome will yield new approaches to therapy.

NIH supports research related to Cushing's syndrome at medical centers

throughout the United States. Scientists are also treating patients with

Cushing's syndrome at the NIH Warren Grant Magnuson Clinical Center in

Bethesda, land. Physicians who are interested in referring a patient may

contact Dr. P. Chrousos, Developmental Endocrinology Branch, NICHD,

Building 10, Room 10N262, Bethesda, land 20892, telephone (301)

496-4686.

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Where Can I Find More Information? The following materials can be

found in medical libraries, many college and university libraries, and

through interlibrary loan in most public libraries.

, R. " Contemporary Diagnosis and Management of Pituitary

Adenomas, " Park Ridge, Illinois: American Association of Neurological

Surgeons, 1991.

DeGroot, J., ed., et al. " Cushing's Syndrome, " Endocrinology.

Vol. 2, Philadelphia: W. B. Saunders Company, 1995. 1741-1769.

Isselbacher, Kurt J., ed., et al. " Cushing's Syndrome Etiology, "

on's Principles of Internal Medicine. Vol. 2, No. 13, New York:

McGraw-Hill Book Company, 1994. 1960-1965.

, D., ed, et al. " Hyperfunction: Glucocorticoids:

Hypercortisolism (Cushing's syndrome), " Textbook of Endocrinology,

No. 8, Philadelphia: W.B. Saunders, 1992; 536-562.

Conn, R.B., Gomez, T., Chrousos, G.P., " Current Diagnosis, " No. 8,

Philadelphia: W.B. Saunders 1991, 868-872.

NCI Research Report: Cancer of the Lung. Prepared by the Office of

Cancer Communications, National Cancer Institute, NIH Publication No.

93-526.

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What Other Resources Are Available? Cushing's Support and Research

Foundation, Inc.

65 East India Row 22B

Boston, Massachusetts 02110

(617) 723-3824 or (617) 723-3674

Louise L. Pace, Founder and President

Pituitary Network Association

P.O. Box 1958

Thousand Oaks, CA 91358

(805) 499-9973

Fax: (805) 480-0633

http://www.pituitary.org

Email: pna@...

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This e-text is not copyrighted. NIDDK encourages users to duplicate

and distribute as many copies as needed. Printed single copies may be

obtained from the Office of Communications and Public Liaison, NIDDK, 31

CENTER DRIVE, MSC 2560, Bethesda, land 20892-2560.

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NIH Publication No. 02-3007

June 2002

never felt so low after a Dr visit...

>

> Hi All,

> Well at least I know my weight is not my fault...but it still sucks.

> The Dr. took one look at my chart and said " 'whoa' you gained 25 lbs

> since I last saw you " I just thought weight gain was an acceptable

> part of having hypothyroidism. My doc says something is definately

> wrong since I told him I am doing everything I can to lose weight and

> have been unsuccessful. So, he is testing my tsh, if that comes back

> abnormal we will of course adjust my dose, if it comes back normal he

> is going to test further for other adrenal and endocrine disorders.

> I was so sad after leaving his office, for a doctor to actually see

> my weight gain really is hard for me, since I have been so thin and

> in shape, until now of course. Anyway, b/c of the unexplainable

> weight gain he suspects cushings. What is that? If anyone has some

> encouraging words for me I would love it if you shared it with me

>

> Thanks

>

September 4, 2004

Are you on T4 only med? T3 helps weight loss. Actually the doc should be

suspecting hypoadrenals, not Cushings. The best docs for thyroid/adrenals

are holistic or Broda docs http://www.brodabarnes.org

Gracia