Hypercortisolism

Also known as Cushing's syndrome

A disease caused by increased production of cortisol or by excessive use of cortisol or other steroid hormones.

Hypercortisolism is a condition that results from an excess of cortisol, a hormone produced by the adrenal glands. The most common cause of Hypercortisolism is Cushing's disease caused by excessive production of adrenocorticotropic hormone (ACTH) by the pituitary gland. ACTH stimulates the adrenal glands to produce cortisol.

Hypercortisolism can be caused by a tumor of the pituitary gland, a tumor of the adrenal gland, a tumor somewhere other than the pituitary or adrenal glands (ectopic Hypercortisolism), or by long-term use of corticosteroids (drugs commonly used to treat conditions, such as rheumatoid arthritis and asthma).

Risk factors are adrenal tumor or pituitary tumor, chronic therapy with corticosteroids, and being female.

Hypercortisolism Symptoms

• moon face (round, red, and full)
• buffalo hump (a collection of fat between the shoulders)
• central obesity with protruding abdomen and thin extremities
• weight gain
• weakness
• backache
• headache
• acne or superficial skin infections
• thin skin with easy bruising
• thirst
• increased urination
• purple striations on the skin of the abdomen, thighs, and breasts
• mental changes
• impotence or cessation of menses
• facial hair growth

Additional symptoms of Hypercortisolism that may be associated with this disease:

• weight gain (unintentional)
• skin spots, red
• skin blushing/flushing
• muscle atrophy
• fatigue
• bone pain or tenderness

Basic explanation of Hypercortisolism Symptoms

One common symptom is weight gain. Fat deposits can form around your stomach and upper back. Arms and legs stay thin and don't usually get fatter.

Your skin gets thinner and is easily bruised. Cuts, scratches and insect bites take a long time to heal. Pink or purple stretch marks may form on your skin. Your face gets round and puffy.

You may feel tired and have weak muscles. You may feel depressed. Women usually have irregular menstrual periods and may grow thick or more visible body hair.

High blood pressure, osteoporosis and diabetes can be signs of Hypercortisolism or disease.

Infections take longer to heal. If you often get skin infections or other infections, especially if the infections are unusual, you may have Hypercortisolism or disease.

Hypercortisolism Diagnosis

Your doctor may start by asking you questions and doing a physical exam. If the cause is a medicine you are taking, no tests are needed. If your doctor thinks that you have Hypercortisolism or disease, but no medicines are causing it, you may need to have some blood and urine tests.

Your doctor may ask you to collect your urine for 24 hours. Be sure to do what the doctor tells you to do for this test. Your doctor may have you take a medicine called dexamethasone before your blood or urine is collected. This tests your body's response to steroids.

Hypercortisolism Diagnosis - Tests to confirm high cortisol level:

• cortisol, urine
• dexamethasone suppression test
• serial serum cortisol levels do not show diurnal variations

Hypercortisolism Diagnosis - Tests to determine the cause:

• ACTH
• cranial MRI or cranial CT scan may show pituitary tumor
• abdominal CT may show adrenal mass

More detailed information about Hypercortisolism Diagnosis

Most people who appear to have some of the classic physical features of Hypercortisolism (cushingoid appearance) do not actually have the disease. After iatrogenic Cushing's is excluded, other causes of this appearance cn be polycystic ovary syndrome (androgen excess from the ovaries), ovarian tumors, congenital adrenal hyperplasia, ordinary obesity, excessive alcohol consumption, or just a family tendency to have a round face and abdomen with high blood pressure and high blood sugar.

Because Hypercortisolism is a rare but serious disorder, it is very important to carefully exclude (rule out) other disorders and then separate the different types, leading eventually to a specific cause that can be treated. This process of testing and excluding usually takes days to weeks and requires a lot of patience and cooperation by the person being tested.

After the initial history, physical exam and routine blood tests, the first step is to prove cortisol excess with specific blood and 24 hour urine tests for cortisol. Inappropriate cortisol production will then be evaluated by doing a dexamethasone suppression test. Dexamethasone (steroid) pills are given by mouth, then blood and urine are collected for cortisol and other adrenal hormones. A screening test might be done initially with an overnight test, but if it is abnormal, usually a 4 day test divided into low and high dose dexamethasone is needed. To separate ACTH dependent from independent types, a blood test for ACTH in the morning is done. Blood and urine tests for adrenal androgens are useful. Testing with other drugs, such as metyrapone and CRH (corticotropin releasing hormone) may also be needed.

Once all of the blood and urine results are analyzed, they will establish whether some type of Hypercortisolism is present, and should indicate whether the disease is ACTH dependent (pituitary or ectopic) or independent (an adrenal tumor). Localizing techniques such as CT or MRI are then used to find the tumor. Often a pituitary tumor is tiny and hard to find, so a special test of the release of ACTH from both sides of the pituitary (petrosal sinus sampling) might be needed. Small tumors producing ectopic ACTH are also sometimes difficult to localize and require repeated scans and x-rays.

Hypercortisolism Treatments

If you have Cushing's disease, a doctor will remove the tumor from your pituitary gland. The surgery is usually a success. Radiation treatments are sometimes used after surgery. You'll need to take cortisone-like medicines for several months after the tumor is removed. You'll need to follow your treatment plan very carefully.

Treatment for Hypercortisolism caused by high doses of steriods

If the Hypercortisolism is a side effect of taking high doses of steroid hormones (iatrogenic), withdrawing these medicines will allow the body to go back to normal. The ability to taper or stop the steroids, however, depends on the type of disease being treated and the pattern of response. Sometimes, steroids cannot be totally stopped or may be reduced only to a limited degree because the illness being treated would worsen. In that case, some degree of persistent Hypercortisolism would remain as an unwanted side effect. Treatment of the effects of steroid excess would include management of high blood sugar with diet and medications, replacement of potassium, treatment of high blood pressure, early treatment of any infections, adequate calcium intake and appropriate adjustments in steroid doses at times of acute illness, surgery or injury.

Surgery as a treatment for Hypercortisolism

Cushing's disease is best treated with the surgical removal of the pituitary tumor, usually with a technique called transsphenoidal resection (behind the nose) by a neurosurgeon. Occasionally, the entire pituitary gland will need to be removed or injured in order to cure the Cushing's disease, leaving the person with a deficiency of ACTH and the other pituitary hormones. This can be treated by giving replacement hormones for cortisol, thyroid and gonadal (sex) hormones. Fertility can be restored with special hormonal therapies. If the pituitary tumor cannot be removed, radiation therapy to the pituitary can be used, but the improvement in the Hypercortisolism is much slower. Before transsphenoidal surgery became available, the surgical removal of both adrenal glands was common, but this always produced adrenal insufficiency and sometimes caused large ACTH producing pituitary tumors to grow (called Nelson's syndrome). That is why pituitary surgery rather than adrenal surgery is usually preferred for Cushing's disease.

Ectopic ACTH producing tumors are usually malignant (cancer). Removing this cancer or treating it with radiation or chemotherapy may help in improving the Hypercortisolism. If the tumor is benign, or it can be completely removed, surgery may be a cure. Most of the time, reduction of the cortisol production from the adrenals with medications such as metyrapone, amino-glutethimide or ketoconazole is useful while the ACTH-producing tumor is treated.

Adrenal adenomas are always treated by surgically removing the tumor with either an abdominal or side (flank) incision. The other adrenal is left in, and will grow back to normal size or function. After the surgery, replacement steroid hormones are given and slowly tapered over a few months as the remaining adrenal responds to the normal ACTH production from the pituitary.

Adrenal carcinomas (cancer) can be cured if removed early. Unfortunately, they are usually discovered after they have already spread beyond the adrenal gland and are then not curable. Chemotherapy including o, p'DDD and other medicines are often used to try to control the tumor but do not cure it. The excess cortisol production can be controlled with o, p'DDD or by other medications like those mentioned for ectopic ACTH production: metyrapone, aminoglutethimide and ketoconazole. These medicines can be used to treat any form of inoperable or incurable Hypercortisolism, including Cushing's disease, but they can have serious side effects and require very careful monitoring and balancing with steroid hormone replacement therapies. Surgical cure of the primary cause of the Hypercortisolism is always the best, if possible