The human endocrine system is made of glands that produce and secrete hormones (chemical substances) that control and regulate the activity of the cells and organs of the body. The different glands work in combination with each other. The pituitary gland found at the base of the brain is the mastermind of the glands, and with the help of the hypothalamus (another gland) can order the rest of the glands in the system to perform in certain ways.
When your body tissues are exposed to an abnormally high level of the hormone cortisol (produced by the adrenal glands) for long periods of time it is called Cushing’s syndrome. This may also be called hypercortisolism, and it is a fairly uncommon disease. It usually occurs in adults between the ages of 20 and 50. Cushing’s syndrome affects approximately 10 to 15 out of every million people per year.
In this article, I will cover the following topic areas:
What are the symptoms of Cushing’s Syndrome?
What are the causes of Cushing’s Syndrome?
Diagnosing Cushing’s Syndrome
How Is Cushing’s Syndrome treated?
The adrenal glands are triangular-shaped glands that sit on top of each kidney. When the pituitary gland sends a certain message to the adrenal glands, the outer portion of each adrenal gland produces several different hormones of its own, including the corticosteroids. These are the hormones that help control the body’s metabolism. The adrenal hormones also control our levels of sodium and potassium, our immune system, and they play a role in our sexual function too. It is truly amazing what these tiny amounts of hormones can do in the body. They have the ability to make so many changes with the smallest effort.
Symptoms vary from person to person, but they make take the form of some or many of the following:
- Upper body obesity, weight gain
- Increased fat deposits around the neck area, upper back, midline
- Relatively thin legs and arms
- Rounded face
- Purplish-pink stretch marks on the arms, breasts, abdomen, and thighs
- Skin that is thin, fragile, and bruises easily
- Skin that heals slowly when injured
- Muscle weakness
- High blood pressure
- Glucose intolerance
- Increased thirst
- Increased urination
- Bone weakness leading to fractures
- Severe fatigue
- Anxiety, irritability
- Cognitive problems
Men may also have erectile dysfunction, diminished or absent sexual interest, and decreased fertility. Women may find absent or irregular menstrual periods and extra hair growth on their faces, chests, necks, abdomens, and thighs. Children with Cushing’s usually have a slower rate of growth and may be overweight to obese.
Some other, unrelated, conditions can cause similar symptoms without excessive cortisol. Polycystic ovary syndrome can cause excessive hair growth, menstrual abnormalities, weight gain, and even diabetes. Metabolic syndrome can cause excessive weight around the central region, insulin resistance, high blood pressure, and high levels of cholesterol. These are all similar symptoms to those caused by Cushing’s syndrome.
Some people suffer from this condition because they take glucocorticoid hormones such as prednisone for treatment of other diseases including rheumatoid arthritis, asthma, lupus, or other inflammatory diseases. Glucocorticoids are also used in treatments after transplantation procedures to suppress the immune system so that the body will not reject the newly transplanted organ.
Overproduction of cortisol by the body
Some develop Cushing’s because the body overproduces cortisol. The endocrine chain of command starts in the brain with the hypothalamus which sends its corticotropin-releasing hormone (CRH) to the pituitary, which in turn causes the pituitary to send its stimulating adrenocorticotropin hormone (ACTH) to the adrenals. The adrenals receive the ACTH and release their cortisol into the bloodstream.
The cortisol sent out by the adrenals is vital to our bodies in that it keeps our cardiovascular system working and helps to maintain blood pressure. It is important in controlling the metabolism of our foods in breaking down the carbohydrates, proteins, and fats. Another vital purpose of the cortisol in our bodies is to help the body respond to stress. This is why it is found in unusually higher levels in pregnant women in their last months of pregnancy and in elite athletes. Anytime people are going through high periods of stress, the cortisol levels are found to be higher. This would include those who suffer from malnutrition, alcoholism, and depression.
The body regulates itself in most cases with respect to cortisol levels. When the amount of cortisol in the blood reaches the optimal level, the hypothalamus and the pituitary each release less of their particular hormones (CRH and ACTH). This helps the adrenals to release an amount of cortisol that meets the body’s needs and remains healthy and balanced. However, in certain circumstances the amount of cortisol released may be too much for the body to handle.
Pituitary adenomas are noncancerous tumors in the pituitary gland that secrete excessive amounts of ACTH. This is perhaps the most common cause of Cushing’s syndrome, and it affects women five times more than men.
When the tumors are found outside of the pituitary gland but still produce excessive ACTH the condition is called ectopic ACTH syndrome. Lung, thymoma, pancreatic islet cell tumors, and medullary carcinomas of the thyroid are the most common in this group.
Hereditary Cushing’s syndrome rarely occurs. Some families however tend to develop tumors within the endocrine glands. Young adults and children may develop tumors of the adrenal glands that produce cortisol. The parathyroid glands, pituitary, and pancreas may also develop hormone-secreting tumors called Multiple Endocrine Neoplasia Type I (MEN I).
Since the signs and symptoms of Cushing’s syndrome involve progressive body changes, it may be difficult to know when to see your physician. The most common sign, especially when using corticosteroid medications to treat other conditions such as arthritis, inflammatory bowel disease, asthma, et cetera, is weight gain and fat deposits around the neck, upper back, face, and around the waist. Skin changes to watch for include stretch marks on the arms, thighs, abdomen, and breasts, along with acne and skin that bruises easily.
If you are experiencing these symptoms in combination with any of the other signs including fatigue, a new rise in blood pressure, emotional changes, or headaches, a trip to your doctor would be prudent. Because many of these symptoms can be caused by other conditions, the physician will review your medical history, give you a complete physical examination, and perform laboratory tests which may also include x-rays of the adrenal or pituitary glands.
Laboratory tests to diagnose Cushing’s syndrome
Because there is no single test that will provide a definitive answer, doctors usually elect to use more than one. There are three common tests used to diagnose Cushing’s syndrome.
- 24-hour urinary free cortisol level. This test involves collecting a patient’s urine several times over a 24-hour window, and then testing it for cortisol. An adult with levels of cortisol higher than 50 to 100 mcg per day would be considered high.
- Midnight plasma cortisol and late-night salivary cortisol measurements. Cortisol is usually suppressed at night, but with Cushing’s syndrome it is not. These measurements are found in the blood and saliva. If the level is higher than 50 nmol/L, it is highly suggestive of Cushing’s syndrome. This is done in the hospital over 48 hours to avoid levels caused by stress.
- Low-dose dexamethasone suppression test (LDDST). Dexamethasone is a synthetic glucocorticoid. The patient is given a low dose of dexamethasone orally every six hours for 48 hours. Urine is collected before the drug is given and then several other times during each of the days. Since glucocorticoids alert the pituitary to release ACTH, the response after taking dexamethasone would be a drop in cortisol levels. If cortisol levels do not drop, Cushing’s syndrome would be suspected. This test may show false results if the patient has depression, alcoholism, acute illness, or stress.
Another test is used for patients who have high levels of cortisol but do not develop some of Cushing’s syndrome’s more progressive symptoms such as fractures of bone, muscle weakness, and skin thinning. This is often called pseudo-Cushing’s syndrome. People with anxiety disorders or depression, poorly controlled diabetes, excessive alcohol users, or very obese may have this disorder but not require treatment to the endocrine glands. This test dexamethasone-corticotropin-releasing hormone (CRH) test will distinguish the pseudo-Cushing’s syndrome from mild cases of Cushing’s syndrome.
Laboratory tests to find the cause of Cushing’s syndrome
Once Cushing’s syndrome has been diagnosed, it is necessary to find which part of the body is the culprit in producing the excessive cortisol. There are several tests to do this. Your physician or endocrinologist will determine which will work best in your situation.
- CRH stimulation test. This test (as above) helps determine whether the excessive cortisol is coming from the pituitary adenoma or from an ectopic ACTH syndrome source or adrenal tumor. When the CRH is injected, patients with pituitary adenomas usually have a rise in the levels of ACTH and cortisol. This is not often seen in patients with ectopic ACTH syndrome or with adrenal tumors.
- High-dose dexamethasone suppression test (HDDST). This test is the same as the LDDST but uses higher doses of dexamethasone. The high doses of dexamethasone will normally suppress cortisol levels in patients with pituitary adenomas but not in those with ectopic ACTH producing tumors.
- Radiologic imaging. These imaging tests look directly at the endocrine glands. By viewing the size and shape of the pituitary and adrenal glands, radiologists can determine if there is a tumor existing in either. Either CT or MRIs are used for the tests. The images are used after a diagnosis has already been made as sometimes there are benign tumors found in the glands (called incidentalomas) that do not produce harmful quantities of hormones. Often in pituitary glands, tumors may not even be visualized.
- Petrosal sinus sampling. This test is one of the best ways to separate pituitary from ectopic causes of Cushing’s syndrome but is not always necessary. Blood is drawn from the petrosal sinuses (veins that drain the pituitary) by inserting tiny tubes through a vein in the upper thigh or groin. Anesthesia and sedation are used. CRH is often given to improve results. ACTH is then measured and compared with ACTH in a forearm vein. Higher levels of ACTH in the sinuses indicate a pituitary adenoma. Similar levels in both suggest ectopic ACTH syndrome.
Pituitary Adenomas. The pituitary adenomas are usually removed surgically using a microscope. It is most often done through a nostril or an opening below the upper lip. It is meticulous tiny surgery requiring an experienced surgeon and produces more than an 80 percent cure rate in most cases. After surgery, the ACTH level drops dramatically and the patient is often supplemented with synthetic cortisol for a year or two, sometimes requiring life-time replacement.
Radiation to the pituitary is another treatment. This is given over a six-week timeframe with a improvement in 40 to 50 percent of adults and up to 85 percent in children.
A third method of correcting pituitary adenomas is by gamma knife stereotactic radiosurgery. This is given in a one-dose treatment, and it may take several months to years for the patient to feel better from the radiation treatment alone, but it may also be combined with drugs that inhibit cortisol for a quicker recovery. Drugs may also be used alone or in combination with other methods, and some do have certain side effects.
Ectopic ACTH syndrome. When excessive cortisol is produced by these sources, the tissue that is secreting the ACTH must be totally eliminated. To do this physicians will use several methods, sometimes in combination. These include surgery, radiation, chemotherapy, and immunotherapy. The choice would depend upon the type of cancer and how far it has spread in the body. Often the drugs will be used because often the tumors are difficult to find.
Adrenal tumors. Surgery is the main choice in this location. Adrenalectomy (removing entire gland) will help stop overproduction.