CUSHING’S SYNDROME

Anatomy and PhysiologyAdrenal Medulla• The adrenal medulla functions as

part of the autonomic nervous system. Stimulation of preganlglionic symphatethic nerve fibers, which travel directly to the cells of the adrenal medulla, causes release of the cathecolamine hormones epinephrine and norepinephrine.

Adrenal Cortex • A functioning adrenal cortex is

necessary for life; adrenocortical secretions make it possible for the body to adapt to stress of all kinds.

Glucocortocoids• are secreted from the adrenal cortex in response to the

release ACTH from the anterior lobe of the pituitary gland.

• The normal functions of cortisol is to stimulates an Anti-Inflammatory response, the catabolism of peripheral fat and protein to provide substrates for Hepatic Gluconeogensis, vascular tone, and bone metabolism.

Mineralocorticoids • Exert their major effects on the electrolytes metabolism.

They act principally on the renal tubular and gastrointestinal epithelium to caused increased sodium ion reabsorption in exchange for excretion of potassium or hydrogen ions.

Androgens (Adrenal Sex Hormones)

Normal Physiology

Cushing Syndrome

• Sometimes called hypercortisolism.• Cushing’s syndrome is a hormonal disorder

caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol.

CausesPituitary Adenoma• Pituitary adenomas cause 70 percent of Cushing’s syndrome cases,

excluding those caused by glucocorticoid use. These benign, or noncancerous, tumors of the pituitary gland secrete extra ACTH. Most people with the disorder have a single adenoma.

Ectopic ACTH Syndrome• Some benign or, more often, cancerous tumors that arise outside the

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

Adrenal Tumors• In rare cases, an abnormality of the adrenal glands, most often an

adrenal tumor, causes Cushing’s syndrome. Most of these cases involve noncancerous tumors of adrenal tissue called adrenal adenomas, which release excess cortisol into the blood.

Familial Cushing’s Syndrome• Most cases of Cushing’s syndrome are not inherited. Rarely, however,

Cushing’s syndrome results from an inherited tendency to develop tumors of one or more endocrine glands.

·Prolonged use of glucocorticoids

·Pituitary Adenoma

·Ectopic ACTH Syndrome

·Adrenal Tumors

·Familial Cushing’s Syndrome

Stimulate hypothalamus to release Corticotropin releasing hormone (CRH)

Anterior Pituitary Gland secretes adrenocorticotropin hormone (ACTH)

Stimulates Adrenal Cortex to release cortisol

Through blood stream

Release of cortisol

HYPERCORTISOLISM

Due to disrupted feedback loop of cortisol

Opthalmic Cataracts Glaucoma

Cardiovascular Hypertensive Heart failure

Endocrine/Metabollic Truncal obesity Moon face Buffalo hump Sodium Retention Hypokalemia Metabolic Alkalosis Hyperglycemia Menstrual irregularities Impotence Altered calcium metabolism Adrtenal Suppressions

Skeletal Osteoporosis Spontaneous fractures Aseptic necrosis of femur Vertebral compression fractures

Dermatologic Thiining of skin Petechiae Ecchymoses Striae Acne

Immune function Decreased

inflammatory responses

Impaired wound healing

Increased susceptibility to infections

Muscular Myopathy Muscle

weakness

Psychiatric Mood

alterations Pyschoses

Signs and Symptoms

Diagnostic Tests

Tests to Diagnose Cushing’s Syndrome

24-hour urinary free cortisol level.• In this test, a person’s urine is collected several times

over a 24-hour period and tested for cortisol. Levels higher than 50 to 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.

Diagnostic Tests

Tests to Diagnose Cushing’s Syndrome

Midnight plasma cortisol and late-night salivary cortisol measurements

• The midnight plasma cortisol test measures cortisol concentrations in the blood. Cortisol production is normally suppressed at night, but in Cushing’s syndrome, this suppression doesn’t occur. If the cortisol level is more than 50 nanomoles per liter (nmol/L), Cushing’s syndrome is suspected. The test generally requires a 48-hour hospital stay to avoid falsely elevated cortisol levels due to stress.

• However, a late-night or bedtime saliva sample can be obtained at home, then tested to determine the cortisol level. Diagnostic ranges vary, depending on the measurement technique used.

Diagnostic Tests

Tests to Diagnose Cushing’s SyndromeLow-dose dexamethasone suppression test (LDDST)• In the LDDST, a person is given a low dose of

dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 2 days. Urine is collected before dexamethasone is administered and several times on each day of the test. A modified LDDST uses a onetime overnight dose.

Dexamethasone-corticotropin-releasing hormone (CRH) test. • This test combines the LDDST and a CRH stimulation test. In

the CRH stimulation test, an injection of CRH causes the pituitary to secrete ACTH. Pretreatment with dexamethasone prevents CRH from causing an increase in cortisol

Tests to Find the Cause of Cushing’s Syndrome

CRH stimulation test.• As a result of the CRH injection, people with pituitary

adenomas usually experience a rise in blood levels of ACTH and cortisol because CRH acts directly on the pituitary. This response is rarely seen in people with ectopic ACTH syndrome and practically never in those with adrenal tumors.

High-dose dexamethasone suppression test (HDDST)• The HDDST is the same as the LDDST, except it uses higher

doses of dexamethasone. This test helps separate people with excess production of ACTH due to pituitary adenomas from those with ectopic ACTH-producing tumors. High doses of dexamethasone usually suppress cortisol levels in people with pituitary adenomas but not in those with ectopic ACTH-producing tumors.

Tests to Find the Cause of Cushing’s Syndrome

Radiologic imaging: direct visualization of the endocrine glands

• Imaging tests reveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present.

Petrosal sinus sampling• This test is not always required, but in many cases, it is the

best way to distinguish pituitary from ectopic causes of Cushing’s syndrome. Samples of blood are drawn from the petrosal sinuses—veins that drain the pituitary—by inserting tiny tubes through a vein in the upper thigh or groin region. A local anesthetic and mild sedation are given, and x rays are taken to confirm the correct position of the tubes. Often CRH, the hormone that causes the pituitary to release ACTH, is given during this test to improve diagnostic accuracy.

Drug Mechanism of action

Indication Adverse Effect Nursing Responsibilities

Metytrapone(Metopirone)

is an inhibitor of endogenous adrenal corticosteroid synthesis

Metopirone is a diagnostic drug for testing hypothalamic-pituitary ACTH function

Nausea, vomiting, abdominal discomfort or pain.

Central Nervous System: Headache, dizziness, sedation.

Dermatologic System: Allergic rash.

Hematologic System: Rarely, decreased white blood cell count or bone marrow depression.

Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity.

Aminoglutethimide(Cytadren)

is an inhibitor of adrenocortical steroid synthesis

Cytadren is indicated for the suppression of adrenal function in selected patients with Cushing's syndrome.

allergic reaction (including difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); or fainting or dizziness,

especially when standing up.

Patients should be warned that drowsiness may occur and that they should not engage in other activities that may become hazardous because of decreased alertness.Patients should also be warned of the possibility of hypotension and its symptoms

Mitotane(Lysodren)

Directly suppresses activity of adrenal cortex and changes the peripheral metabolism of corticosteroids.

Indicated in the treatment of inoperable adrenal corticalcarcinoma of both functional and nonfunctional types.

feeling like you might pass out;

fast or pounding heartbeats;

warmth, redness, or tingly feeling under your skin;

sweating, cold or clammy skin;

high fever, chills, uncontrolled shaking;

blurred or double

LYSODREN should be temporarily discontinued immediately following shock or severe trauma, since adrenal suppression is its prime action. Exogenoussteroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids.

Surgical Management

Transsphenoidal Hypophysectomy• During the operation, your nose was

packed with sponge packings to absorb any drainage from the site of surgery. In addition, small plastic supports (called stents) were attached to the septum of your nose with a stitch. The packings and stents will be removed before you leave the hospital or shortly thereafter. The other stitches in the gum line will dissolve on their own. You may feel a numbness in your upper lip, gum or teeth. This generally improves or disappears over time.

Dos and Don'ts• You must not blow your nose after this type of operation.

Doing so could disrupt the healing process and lead to spinal fluid leaks or other problems.

• A small amount of bloody or mucous-type drainage from the nose is expected. However, if you develop continued watery drainage you should contact your physician immediately.

• You may have headache or some pain after the operation. You may be given a pain medication prescription to take home with you. If your pain is mild and you would prefer to take an over-the-counter medication you may take acetaminophen (Tylenol or Extra-Strength Tylenol) according to the package directions. Take all medications prescribed for you and do not stop taking them abruptly.

Contact you physician immediately if:• You develop a rash, upset stomach or other problems that may be

related to medication.• You develop high fever and a stiff neck.• You develop neurological problems such as slurred speech, double

vision or loss of vision, weakness in your face or any arm or leg, or have a seizure (convulsion).

• You notice swelling, redness or pain in your foot or leg. This could indicate a blood clot in the leg, a serious problem that may occur after surgery. Symptoms such as shortness of breath, severe chest pain or coughing up blood could be a sign of a blood clot moving to the lung or another serious medical problem. If you have any of these symptoms you should come the emergency room or contact us immediately.

• Excessive thirst or urination could be a sign of a hormone problem after the surgery. You should contact your endocrinologist (hormone specialist) if these symptoms continue.

Adrenalectomy • Adrenalectomy is the surgical removal of one or

both adrenal glands. The adrenal glands are paired endocrine glands—one located above each kidney—that produce hormones such as epinephrine, norepinephrine, androgens, estrogens, aldosterone, and cortisol. Adrenalectomy is usually performed by conventional (open) surgery; however, in selected patients, surgeons may use laparoscopy . With laparoscopy, adrenalectomy can be accomplished through four very small incisions.

Before treatment After treatment

Nursing Management

Decreasing risk for injury• Establishing a protective environment will help to prevent

falls, fractures and other injuries to bones and soft tissues. The patient who is very weak may require assistance from the nurse in ambulating to prevent falls or bumping.

• Food high in protein, calcium and vitamin D are recommended to minimize muscle wasting and osteoporosis.

Decreasing risk for infection• The patient should avoid unnecessary exposure to others

with infections.• The nurse frequently assesses the patient for subtle signs of

infection because the anti inflammatory effects of corticosteroids may mask the common signs of inflammation and infection.

Nursing Management

Encouraging Rest and Activity• Weakness, fatigue and muscle wasting make it difficult

for the patient with Cushing syndrome to carry out normal activities. Yet the nurse should encourage moderate activity to prevent complication of immobility ad promote instead self- esteem.

Improving Body Image• The patient may benefit from discussion of the effects

the changes had on his or her self concept and relationship with others. Weight gain and edema may be modified by a low carbohydrate; low sodium diet and high protein intake may reduce some of other bothersome symptoms.

Nursing Management

Promoting Skin Integrity• Meticulous skin care is necessary to avoid traumatizing the

patient’s fragile skin. Use of adhesive tape is avoided because it can irritate the skin and tear the fragile tissue when the tape is removed.

• The nurse frequently assesses the skin and bony prominences and encourages and assists the patient to change position frequently to prevent skin breakdown.

Improving Thought Process• Explanation to the patient and family members about the cause

of emotional instability are important in helping them cope with the mood swing, irritability and depression that may occur.

• Psychotic behavior may occur in a few patients in few patients and should be reported.