Cushing's syndrome

Definition

Cushings's syndrome (hypercortisolism, hyperadrenocorticism) is a condition in which the body is subjected to abnormally high levels of the hormone cortisol for a prolonged period of time. This syndrome is named after Dr. Harvey Cushing, who initially discovered and described this affliction.

High levels of cortisol may arise from disease states within the body, as well as a side effect of prolonged use of some anti-inflammatory medications (corticosteroids). Long-term exposure to abnormally high levels of cortisol can affect the many systems of the body influenced by the hormone such as the breakdown and storage of food, the formation of bone, mental and emotional responses to stress, and the immune system, among others. As such, the presentation of symptoms can be variable, depending upon the extent of the imbalance

Demographics

This syndrome is relatively rare, arising in adults from age 20–50. Approximately 10–15 people per million are afflicted with this disease each year.

Causes and symptoms

Many functions within the body are regulated by a system of glands (endocrine glands), which include the pituitary, pineal, thyroid, thymus, adrenal, pancreas, ovaries (females) and testes (males). These glands secrete special, powerful substances called hormones into the bloodstream, which then travel to different parts of the body to regulate specific functions.

Cortisol is one type of hormone produced by the adrenal gland, and is formed in a series of actions, within the body. Under normal conditions, a part of the brain, the hypothalamus, secretes a hormone called CRH (Corticotrophin Releasing Hormone), which acts on the pituitary gland. In response to this stimulus, the pituitary gland secretes another hormone called ACTH (Aderenocorticotrophin), which in turn causes the adrenal glands to secrete the hormone cortisol.

Cushing's syndrome may occur when there is too much cortisol from medication use. The prolonged, extended use of high levels of anti-inflammatory corticosteroid medications, such as prednisone, for the treatment of conditions such as allergies, asthma, rheumatoid arthritis , and some autoimmune diseases may raise cortisol levels.

However, it may also result from a hormonal imbalance in which too much cortisol is produced by the body due to an abnormality. There can be several reasons for this including:

• The occurrence of benign, non-cancerous tumors (adenomas) in the pituitary gland that release ACTH, stimulating the adrenal glands to produce excess cortisol. This is called Cushing's disease affecting more women than men.
• The presence of an abnormality or tumor in the adrenal gland that directly increases cortisol production.
• Benign or cancerous tumors arising in areas such as the lung, pancreas, thyroid, that produce ATCH (ectopic ACTH), resulting in increased cortisol production.
• Although most cases of Cushing's are not inherited, there may be a tendency in some families to develop tumors in the endocrine glands due to Familial Cushing's syndrome.

The hormone cortisol is involved in the control of many body activities including metabolism (influencing the levels of blood sugars and lipids), blood pressure , responses to stress , as well as the formation of bone, among others. As the influences of cortisol are so widespread throughout the body, the symptoms are variable and may include:

• a rounded, bloated face
• weight gain in the form of central obesity in the trunk of the body (chest and abdomen)
• “buffalo hump” of fat on the upper back, between the shoulders
• flushing of the face
• fatigue
• bone loss (osteoporosis)
• hypertension (high blood pressure)
• purple colored stretch marks
• high blood sugar (diabetes)
• mental and emotional symptoms such as depression, anxiety, and irritability
• thin skin that can become easily bruised
• difficulty healing wounds
• acne
• men: impotence (erectile dysfunction), reduction in fertility, and reduced sex drive
• women: abnormal hair growth on body (hirsutism), irregularity or cessation of menstrual periods (amenorrhea)

The presence of symptoms depends on the age, overall health, and activity level of a person, and as such, not all symptoms may be present in a person with Cushing's.

Diagnosis

Early diagnosis is essential for timely medical intervention to reduce the effects of high cortisol levels on the body. If the disease is suspected, it is very important to get testing as soon as possible to obtain medical intervention and improve prognosis. For example, if an individual has been on high levels of corticosteroids as part of a treatment, then begins to develop the symptoms of Cushing's syndrome, further investigation is warranted.

Diagnosis of Cushing's syndrome can be very challenging, as it shares symptoms with other conditions. However, there are several tests that may be utilized by physicians including:

• Saliva Test: In normal individuals, the levels of cortisol in the saliva are usually low between 11:00 pm and midnight. The Late-Night saliva test involves collection of saliva in sampling tubes during this time to determine if cortisol levels are elevated. This test is relatively easy to perform, and is quite sensitive as determined from studies world-wide.
• Blood Test: In the Dexamethasone Suppression test, the patient is given a very low dose of a steroid hormone, dexamethasone, that usually reduces cortisol production to very low levels, that are detected in the blood. However, those with Cushing's syndromes will have higher levels following dexamethasone. Sometimes, those patients with mild Cushing's may still fall within normal ranges, so this test may be accompanied by others. In some cases this test may be accompanied by a Dexamethasone CRH test to study the stimulation of cortisol production. Levels of ACTH may also be assessed.
• Urine Cortisol Test: This test involves collection of urine over a 24 hr period to look for elevated free cortisol levels. However, additional testing may be needed to verify the diagnosis, as milder cases of Cushing's syndrome may fall within normal ranges, and urine cortisol levels may be elevated in other conditions.
• Imaging Tests: Tests may be performed to look for the tumors that might be causing excess cortisol production in various areas of the body, especially the brain (pituitary gland). These tests are magnetic resonance imaging (MRI) and computerized tomography (CT scan).

QUESTIONS TO ASK YOUR DOCTOR

• What tests need to be performed to determine if a person has Cushing's syndrome?
• Are there any special preparations needed for these tests?
• What is the suspected cause of this?
• What type of symptoms could occur?
• Should medications be adjusted?
• What type of treatment may be needed, what is the expected recovery time, and what are the possible side effects?
• What is the prognosis if this is treated and if it is not?
• What resources are available to assist with coping skills for this condition?
• Should a nutritionist be consulted?

Treatment

The method used to treat Cushing's syndrome is dependant upon the underlying reasons. If the cause is due to medication use, the physician may reduce the dose of medication or prescribed another treatment. This must be done gradually, however, to maintain proper hormone function. Patients should follow their physician's instructions, and not abruptly stop their medication, as this may cause problems. If excess cortisol is produced as a result of a tumor, therapy may involve a combination of surgical intervention, possibly coupled with medication and radiation treatments.

Nutrition/Dietetic concerns

Cushing's syndrome changes the way that food is broken down and stored within the body. This usually results in weight gain, the amount varying for each individual person. Therefore, it is very important to eat a healthy, balanced diet to minimize this effect. Consultation with a nutritionist may be very beneficial. If an elderly person is living in some form of assisted care, it may be helpful to inform caregiver's of dietary restrictions recommended by a physician or nutritionist.

Of particular concern, a patient with Cushing's syndrome should be watchful of their consumption of the following:

• Sugar—The blood sugar levels in Cushing's syndrome patients may elevated beyond normal levels to produce hyperglycemia. Blood sugar may be brought under control through administration of insulin or other medications, or possibly dietary restrictions.
• Cholesterol—Cholesterol levels may be higher than normal and difficult to control, but this can be minimized by following a low fat diet.
• Salt (sodium)—Hypertension (high blood pressure) may be present. Eating too much salt can cause the body to retain water, and therefore promote weight gain. It may be helpful to avoid consumption of salty foods, such as pickles, chips, soda, and some prepared foods. Careful attention to package labeling may be required, as high sodium levels are present in many commonly purchased items.
• Calcium—People with Cushing's syndrome may also have low bone density (thin bones, osteoporosis). Seniors may be especially prone to this condition. Sufficient calcium should be consumed, as well as vitamin D, as recommended by a physician or nutritionist. Consumption of low-fat dairy products may, such as low-fat milk or yogurt, may be consumed to insure adequate calcium intake, and other supplements or medications may be required.

Therapy

In addition to treatments with surgery and medications, a patient may need support in the form of counseling to deal with the anxiety and depression issues associated with Cushing's syndrome. A mental health care professional may need to be included as part of the medical care team.

Prognosis

If the patient receives the proper therapeutic treatment and maintains a good balanced diet, the condition can be successfully managed and brought under control, and in some cases, cured. If left untreated, it may result in death , especially from cardiovascular disease, and thus timely medical intervention is essential.

KEY TERMS

ACTH (Aderenocorticotrophin) —A hormone secreted by the pituitary gland that causes the adrenal glands to secrete the hormone cortisol.

Cushing's disease (hypercortisolism, hyperadrenocorticism) —A condition resulting from a hormonal imbalance in which there are high levels of cortisol, either from medication use or abnormal tumors within the body.

Endocrine system —A system of glands in the body that includes the pituitary, pineal, thyroid, thymus, adrenal, pancreas, ovaries (females) and testes (males). These glands secrete special, powerful substances called hormones into the bloodstream, which then travel to different parts of the body to regulate specific functions.

Prevention

The best prevention is an awareness of symptoms leading to early diagnosis. If a person notices these symptoms, they should be reported. This is especially important for those who may be taking corticosteroid medications. Proper adherence to the physician's recommendations on use of these medications is essential for eliminating side-effects such as Cushing's syndrome.

Caregiver concerns

Care givers should be watchful for the symptoms of Cushing's syndrome, especially for those who are using corticosteroid medications for extended time periods. Physician's recommendations for the use of these medications should be strictly followed, and the elderly are especially vulnerable for developing secondary hypertension using such medications.

People who have Cushing's syndrome are more likely to have anxiety, depression, and low self-esteem (related to appearance changes). They may also have problems with memory. Mental health care may be required to address these issues to bring a patient back to a sense of wholeness and increase coping skills, and a variety of resources are available through the internet to connect with other patients suffering from this affliction.

If a patient is living in an assisted care facility, the staff should be notified of dietary requirements and special needs required to assist with the patient's care and comfort, as well as mental health needs.

Resources

BOOKS

Blevins, L.S.(editor) Cushing's Syndrome. Norwell: Kluwer Academic Publishers, 2002.

http://www.cc.nih.gov/ccc/patient_education/pepubs/nutrcush.pdf

http://www.csrf.net/AboutCushings.htm

http://www.csrf.net/Testing.htm

http://www.cushings-help.com/

The Hormone Foundation Cushing's Syndrome. Chevy Chase: Hormone Foundation, 2005.

http://www.labtestsonline.org/understanding/conditions/cushing.html

http://www.mayoclinic.com/health/cushings-syndrome/DS00470.

http://www.nichd.nih.gov/health/topics/cushingssyndrome.cfm

http://pituitary.mgh.harvard.edu/cushings.htm

http://www.nlm.nih.gov/medlineplus/cushingssyndrome.html

http://www.pituitary.org/news/Articles/CushingsFactSheet.php

ORGANIZATIONS

Cushing's Help and Support, http://www.cushings-help.com/intro.htm.

Cushing's Support & Reseasrch Foundation, 65 E India Row, Suite 22B, Boston, MA, 02110, 617-723-3674, 617-723-3674, [email protected], http://www.csrf.net/index.htm.

Jill Granger M.S.