Cushing Syndrome:Symptoms, Causes, Complications, Diagnosis and Treatment

Cushing syndrome, also called as hypercortisolism or Cushing's syndrome occurs when your body is exposed to high levels of the hormone cortisol for a long time.

Updated: October 30, 2019

Cushing syndrome, also called as hypercortisolism or Cushing's syndrome  occurs when your body is exposed to high levels of the hormone cortisol for a long time.
This can happen for a variety of reasons. But the most common cause is overuse of corticosteroid medications. The condition can also occur when your body makes too much cortisol on its own.
A fatty hump between your shoulders, a rounded face and pink or purple stretch marks on your skin is the hallmark signs of Cushing syndrome. As the symptoms develop gradually, the diagnosis may not be clear for some time. It can also result in high blood pressure, bone loss and type 2 diabetes. Treatments for Cushing syndrome can return your body's cortisol production to normal and noticeably improve your symptoms. The earlier treatment begins, the better your chances for recovery.
Cortisol belongs to the class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. The most important job of cortisol is to help the body respond to stress. In addition to this, cortisol also helps
maintain blood pressure and heart and blood vessel function, slow the immune system's inflammatory response, that is how the body recognizes and defends itself against bacteria, viruses, and substances that appear foreign and harmful and regulate metabolism. The amount of cortisol produced by the adrenal glands is precisely balanced in a healthy person. Cortisol is regulated by the hypothalamus and the pituitary gland. A trigger hormone called corticotropin-releasing hormone (CRH) will be released by hypothalamus, which signals the pituitary gland to produce ACTH. ACTH stimulates the adrenal glands to produce cortisol. Cortisol then signals back to both the pituitary gland and hypothalamus to decrease these trigger hormones after a balanced amount.
The commonest cause of spontaneous Cushing's is a small benign tumor of the pituitary gland. This produces the hormone called ACTH, (adrenocorticotrophic hormone), that goes through the blood stream to the adrenal glands and causes them to release too much cortisol. In this case there is a good chance that an operation on your pituitary gland will solve the problem. Alternatively, there could be a small growth in another part of your body which is having the same effect which is called ectopic ACTH.
In such situation, removing this growth will usually solve the problem. Lastly, there may be a small growth in one of the adrenal glands themselves. An operation will be needed to remove that gland in that situation. However, in some circumstances it may be necessary to remove both adrenal glands to solve the problem which is very rare. If the source of the problem is the pituitary gland, then it is called as Cushing's Disease. Whereas, if it originates anywhere else, then the correct name is Cushing's Syndrome. 

Symptoms of Cushing's Syndrome:

Cushing's affects many parts of the body, both mentally and physically, and affects different people in different ways.

Symptoms of Cushing's include:

  • Excessive and sudden or at times more gradual onset of weight gain around your trunk. Your arms and legs may remain unchanged and can become quite thin compared to your body.
  • Weak muscles, especially in your legs
  • Your face tends to be rounder, a classic symptom of Cushing's known as moon face and you may have developed acne.
  • Your bones may have become weaker (an X-ray may show a fractured rib for instance), due to steroid-induced osteoporosis (thinning and brittleness of bones) and therefore you have an increased risk of fracture
  • You may have developed hypertension and diabetes mellitus
  • You will have excessive thirst and increased urination
  • Some people may also notice a tendency to bruise easily and have deep red/purple stretch marks appearing on the abdomen, similar to those which occur during pregnancy but are more pronounced
  • Women experience irregular periods or stop having them altogether
  • You may also experience excessive hair growth on parts of the body and usually the face in women
  • Men can experience decreased fertility and both men and women can feel a reduction, or absence of sex drive (libido)
  • You may be feeling generally unwell, and more susceptible to infections
  • You will have often mood swings, such as being more irritable, feeling depressed or anxious. In some cases, psychological problems can be severe, even being diagnosed as a nervous breakdown

Children with this condition are generally obese and have a slower rate of growth.
As the progression of the disease is quite slowly and gradually, in most cases, it can go unrecognised in early stage.

Causes of Cushing's syndrome:

The most common cause of Cushing syndrome is the use of corticosteroid medications, such as prednisone, in high doses for prolong period. These medications are prescribed to prevent rejection of a transplanted organ. These are also used to treat inflammatory diseases, such as lupus and arthritis. High doses of injectable steroids for treatment of back pain can also cause this syndrome.
Inhaled steroid medicines taken for asthma and steroid skin creams used for skin disorders such as eczema are generally less likely to cause Cushing syndrome than oral corticosteroids. But, in some individuals, these medications may cause Cushing syndrome, especially if taken in high doses.
One of the main cause of Cushing's syndrome is high level of cortisol in your body. Your body may produce high levels of cortisol for a variety of reasons, including:

  • high stress levels, including stress related to an acute illness, surgery, injury, or pregnancy, especially in the final trimester
  • athletic training
  • malnutrition
  • alcoholism
  • depression, panic disorders, or high levels of emotional stress

Other causes include:

  • a pituitary gland tumor in which the pituitary gland releases too much adrenocorticotropic hormone, which is also known as Cushing's disease
  • ectopic ACTH syndrome, which causes tumors that usually occur in the lung, pancreas, thyroid, or thymus gland
  • an adrenal gland abnormality or tumor

Typically Cushing syndrome isn't inherited, but it is possible to have an inherited tendency to develop tumors of the endocrine glands. When this happens, it is called as Familial Cushing syndrome.

Complications of Cushing's syndrome:

Left untreated, complications of Cushing syndrome may develop which include:

  • Bone loss or osteoporosis, which can result in unusual bone fractures, such as rib fractures and fractures of the bones in the feet
  • High blood pressure or hypertension
  • Type 2 diabetes
  • Frequent or unusual infections
  • Loss of muscle mass and strength

Diagnosis of Cushing's syndrome:

The tests used to diagnose Cushing's are complicated and may take more time. The first tests is done to ensure that Cushing's is present. If Cushing's is likely then further tests are done to pin point the location. This is because most people who gain weight and who have high blood pressure or diabetes or problems with excess hair do not actually have Cushing's.
Initially a physical examination will be conducted by the doctor to look for signs of Cushing syndrome. He or she may suspect Cushing syndrome if you have signs such as rounding of the face or moon face, a pad of fatty tissue between the shoulders and neck (buffalo hump), and thin skin with bruises and stretch marks.
If you have been taking a corticosteroid medication for a long time, you may have developed Cushing syndrome as a result of this medication. If you haven't been using a corticosteroid medication, the below diagnostic tests may help pinpoint the cause:

Urine and blood tests for Cushing's syndrome:

These tests are done to measure hormone levels in your urine and blood which will show whether your body is producing excessive cortisol. You will be asked to collect your urine over a 24 hour period for the urine test. Both the urine and blood samples will be sent to a laboratory to be analyzed for cortisol levels.
Other specialized tests can be done that evaluate the blood and urine to help determine if Cushing syndrome is present and to help identify the underlying source of any excess production. These tests often involve measuring cortisol levels before and after stimulation or suppression with other hormone medications. A tablet called dexamethasone will be given before blood test to see if you have Cushing's. In people who do not have Cushing's, taking this tablet will completely suppress the production of the hormone cortisol. 

Saliva test for Cushing's syndrome:

Cortisol levels normally rise and fall throughout the day. Levels of cortisol drop significantly in the evening in people without Cushing syndrome. For this test, a small sample of saliva can be collected late at night to analyze cortisol levels.
Other test should be done to confirm the diagnosis if cortisol levels are too high.
Imaging tests for Cushing's syndrome:
Computerized tomography scans (CT scan)or magnetic resonance imaging scans (MRI)can provide images of your pituitary and adrenal glands to detect abnormalities, such as tumors.

Petrosal sinus sampling:

This test can help determine whether the cause of endogenous Cushing syndrome is rooted in the pituitary or somewhere else which is ectopic ACTH syndrome. A blood samples are taken from the petrosal sinuses in this test. petrosal sinuses — veins that drain the pituitary glands are the veins that drain the pituitary glands.
A thin tube is inserted into your upper thigh or groin area while you are sedated, and threaded to the petrosal sinuses. Levels of ACTH are measured from the petrosal sinuses, and from a blood sample taken from the forearm. The root cause of cushing is pituitary if ACTH is higher in the sinus sample. If the ACTH levels are similar between the sinus and forearm, the root of the problem lies outside of the pituitary gland. These tests not only help your doctor diagnose Cushing syndrome, but also help rule out other medical conditions with similar signs and symptoms. For example, polycystic ovary syndrome is a hormone disorder in women with enlarged ovaries which shares some of the same signs and symptoms of Cushing, that include excessive hair growth and irregular menstrual periods. Depression, eating disorders and alcoholism also can partially mimic Cushing syndrome.

Treatment of Cushing's syndrome:

The aim of treatment is to lower the high level of cortisol in your body. Treatment plan will depend on the cause of the disease. These include:

Reducing corticosteroid use:

If the cause of Cushing syndrome is long-term use of corticosteroid medications, a change in medication or dosage is necessary. Your doctor will reducing the dosage of the drug over a period of time to keep your Cushing signs and symptoms under control. Instead, noncorticosteroid drugs can be prescribed to managing your asthma, arthritis or other condition. This will allow your doctor to reduce the dosage or eliminate the use of corticosteroids altogether. Never reduce the dose of corticosteroid drugs or stop taking them on your own. You can do this only under supervision of your doctor.
Abruptly discontinuing these medications could lead to deficiency of cortisol levels. Therefore it is advisable to slowly tapering off corticosteroid drugs which will allow your body to resume normal cortisol production.

Surgery for Cushing's syndrome:

Complete surgical removal is recommended if the cause of Cushing syndrome is a tumor. Pituitary tumors are typically removed by a neurosurgeon and the procedure is generally performed through your nose. If a tumor is present in the adrenal glands, lungs or pancreas, it can be removed through a standard operation or in some cases by using minimally invasive surgical techniques, with smaller incisions.
You will need to take cortisol replacement medications to provide your body with the correct amount of cortisol after the surgery. In most cases, normal adrenal hormone production will return, and your doctor can taper off the replacement drugs. However, this process can take up to a year or longer. In some instances, people with Cushing syndrome never experience a resumption of normal adrenal function. In such cases, they then need lifelong replacement therapy.

Radiation therapy for Cushing's syndrome:

If it is not possible to totally remove a pituitary tumor by surgery alone, radiation therapy will be prescribed to be used in conjunction with the operation. In addition, , radiation may be used for people who aren't suitable candidates for surgery.
Radiation can be given in small doses over a six-week period. It can also be given with a technique called stereotactic radiosurgery or Gamma Knife surgery in which, radiation is administered as a single treatment. A large dose of radiation is delivered to the tumor, and the radiation exposure to surrounding tissues is minimized.

Medications for Cushing's syndrome:

Medications can be used to control cortisol production when surgery and radiation don't work. Medications may also be used before surgery in people who have become very sick with Cushing syndrome. Drug therapy may be recommended before surgery to improve signs and symptoms and minimize surgical risk.
Ketoconazole, mitotane and metyrapone are generally prescribed to control excessive production of cortisol at the adrenal gland.
Mifepristone can be used for people with Cushing syndrome who have type 2 diabetes or glucose intolerance. Mifepristone does not decrease cortisol production, but it blocks the effect of cortisol on your tissues. Side effects from these medications may include fatigue, nausea, vomiting, headaches, muscle aches, high blood pressure, low potassium and swelling. More serious side effects, such as neurological side effects and liver toxicity can also happen in some cases.
Pasireotide is recommended if pituitary surgery is unsuccessful or cannot be done. It works by decreasing ACTH production from a pituitary tumor. This medication is given as an injection twice daily. Side effects are fairly common, and may include diarrhea, nausea, high blood sugar, headache, abdominal pain and fatigue.
The tumor or its treatment can cause deficiency of other hormones produced by the pituitary or adrenal gland in some cases. In such situation your doctor will recommend hormone replacement medications for those hormone as well.
If none of these treatment options are appropriate or effective, surgical removal of your adrenal glands is recommended which is known as bilateral adrenalectomy. However, this procedure will cure excess production of cortisol, but will require lifelong replacement medications.

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