Cushing's Syndrome

What is Cushing's syndrome?

Cushing's syndrome is a condition that occurs when your body is exposed to high levels of the hormone cortisol for a long period of time, sometimes called ‘hypercortisolism'. 

What is the difference between Cushing's syndrome and Cushing's disease?
Where Cushing's syndrome is caused by a tumour in the pituitary gland, this is referred to Cushing's disease. The pituitary gland is at the bottom of the brain and controls the body's production of cortisol. These small tumours are usually benign (non-cancerous) but could cause problems with your eyesight if they grow and remain undetected.

Signs and symptoms

• Weight gain, particularly around your midsection and upper back;
• fatigue;
• rounding of your face (often referred to as ‘moon face');
• fatty pad or hump between your shoulders (often referred to as a ‘buffalo hump');
• pink or purple stretch marks (striae) on the skin of your abdomen, thighs, breasts and arms;
• thin and fragile skin that bruises easily;
• slow healing of cuts, insect bites and infections;
• depression, anxiety, irritability or loss of emotional control;
• thicker or more visible body and facial hair (hirsutism);
• irregular or absent menstrual periods in females;
• decreased libido;
• erectile dysfunction in males;
• new or worsened high blood pressure;
• glucose intolerance that may lead to diabetes;
• muscle weakness; and
• bone loss leading to fracture over time.

Causes

The most common cause of Cushing's syndrome is the use of oral corticosteroid medication. The condition can also occur when your body makes too much cortisol.

Your endocrine system consists of glands that produce hormones, which regulate processes throughout your body. Your adrenal glands produce a number of hormones, including cortisol.

Cortisol plays a variety of roles in your body, such as:

• regulating blood pressure;
• keeping the cardiovascular system functioning normally;
• helping your body respond to stress; and
• regulating the way your body converts (metabolises) proteins, carbohydrates and fats in your diet into usable energy.

However, when the level of cortisol is too high in your body, you may develop Cushing's syndrome.

Types of Cushing's syndrome 

Exogenous Cushing's syndrome

Cushing's syndrome can develop from a cause that originates outside of your body. Taking corticosteroid medication in high doses over an extended period of time may result in Cushing's syndrome. These types of medication, such as prednisone, dexamethasone (Decadron®) and methylprednisolone (Medrol®), have the same effects as the cortisol produced by your body.

Your doctor may prescribe corticosteroids to treat inflammatory conditions, such as rheumatoid arthritis, systemic lupus erythematosus and asthma, or to prevent your body from rejecting a transplanted organ. Due to the doses required to treat these conditions often being higher than the amount of cortisol your body would normally need each day, negative side effects of excess cortisol may occur.

People can also develop Cushing's syndrome from injectable corticosteroids - for example, repeated injections for joint pain, bursitis and back pain.

Endogenous Cushing's syndrome

The condition may also be due to your body's own overproduction of cortisol. This may occur from excess production by one or both adrenal glands, or overproduction of the adrenocorticotropic hormone (ACTH), which normally regulates cortisol production. In these cases, Cushing's syndrome may be related to:

• A pituitary gland tumour. A non-cancerous (benign) tumour of the pituitary gland, located at the base of the brain, secretes an excess amount of ACTH, which in turn stimulates the adrenal glands to make more cortisol. This form of the syndrome is called Cushing's disease. It occurs much more often in women and is the most common form of endogenous Cushing's syndrome.

• An ectopic ACTH-secreting tumour. Rarely, when a tumour develops in an organ that normally does not produce ACTH, the tumour will begin to secrete this hormone in excess, resulting in Cushing's syndrome. These tumours, which can be non-cancerous (benign) or cancerous (malignant), are usually found in the lung, pancreas, thyroid or thymus gland.

• A primary adrenal gland disease. In some people, the cause of Cushing's syndrome is excess cortisol secretion that doesn't depend on stimulation from ACTH and is associated with conditions affecting the adrenal glands. The most common of these conditions is a non-cancerous tumour of the adrenal cortex, called an adrenal adenoma. Cancerous tumours of the adrenal cortex are rare, but they can cause Cushing's syndrome as well. Occasionally, benign, nodular enlargement of both adrenal glands can result in Cushing's syndrome.

Complications

If you don't receive prompt treatment for Cushing's syndrome, the following complications may occur:

• loss of bone density (osteoporosis);
• high blood pressure (hypertension);
• kidney stones;
• diabetes;
• frequent or unusual infections; and
• loss of muscle mass and strength.

In the case of Cushing's disease, i.e. when the cause of Cushing's syndrome is a pituitary tumour; it may sometimes lead to other problems, which may interfere with the production of other hormones that the pituitary gland controls.

When to see a doctor

If you are taking corticosteroid medication to treat a condition, such as asthma, arthritis or inflammatory bowel disease and experience signs and symptoms that may indicate Cushing's syndrome, please consult your doctor for an evaluation.

Diagnosis

Cushing's syndrome can be difficult to diagnose. Your doctor will conduct a physical examination, looking for signs of Cushing's syndrome. He/she may suspect Cushing's syndrome if you have signs such as rounding of the face, a pad of fatty tissue at the shoulders and neck, and thin skin with bruises and stretch marks.

If you've been taking a corticosteroid medication for a long period of time, your doctor may suspect that you've developed Cushing's syndrome as a result of this medication. If you haven't been using a corticosteroid medication, these diagnostic tests may help pinpoint the cause:

Urine and blood tests

These tests measure hormone levels in your urine and blood and show whether your body is producing excessive cortisol. Urine and blood samples will be sent to a laboratory to be analysed and to determine cortisol levels.

Saliva test

Cortisol levels normally rise and fall throughout the day. In people without Cushing's syndrome, levels of cortisol drop significantly overnight. By analysing cortisol levels from a small sample of saliva collected late at night, doctors can see if cortisol levels are too high, indicating a diagnosis of Cushing's syndrome.

Imaging tests

Computerised tomography (CT) scans or magnetic resonance imaging (MRI) scans can provide images of your pituitary and adrenal glands to locate abnormalities, such as tumours.

As these tests help your doctor diagnose Cushing's syndrome, they may also rule out medical conditions with similar signs and symptoms. For example, polycystic ovary syndrome (a hormone disorder in women with enlarged ovaries) shares some of the same signs and symptoms as Cushing's syndrome, such as excessive hair growth and irregular menstrual periods. Depression, eating disorders and alcoholism may also share similar signs and symptoms as Cushing's syndrome.

Treatment

Treatment for Cushing's 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. Treatments for Cushing's syndrome are designed to lower the high levels of cortisol in your body. The best treatment for you depends on the cause of the syndrome. Treatment options include:

Reducing usage of corticosteroid

If the cause of Cushing's syndrome is long-term use of corticosteroid medication, your doctor may be able to keep the signs and symptoms under control by reducing the dosage of the drug over a period of time, while still adequately managing your asthma, arthritis or other condition. For many of these medical conditions, your doctor can prescribe non-corticosteroid medication, which will allow him/her to reduce the dosage or eliminate the use of corticosteroids altogether.

Don't reduce the dose or stop the usage of corticosteroid medication without first consulting your doctor. Suddenly stopping the use of this medication could lead to deficient cortisol levels. Slowly reducing the use of corticosteroid medication allows your body to resume normal cortisol production.

Surgery

If the cause of Cushing's syndrome is a tumour, your doctor may recommend complete surgical removal.

After the operation, you'll need to take cortisol replacement medication to provide your body with the correct amount of cortisol. In most cases, you'll eventually experience a return of normal adrenal hormone production, and your doctor can decrease replacement medication. However, this process can take up to a year or longer. In some instances, people with Cushing's syndrome never experience a resumption of normal adrenal function; they then need lifelong replacement therapy.

Radiation therapy

If the surgeon can't totally remove the pituitary tumour, he/she will usually prescribe radiation therapy to be used in conjunction with the operation. Radiation may also be used for people who aren't suitable candidates for surgery. Radiation can be given in small doses over a six-week period, or by a technique called stereotactic radiosurgery or gamma-knife radiation. In this procedure, which is administered as a single treatment, a large dose of radiation is delivered to the tumour and a minimised dose is delivered to the surrounding tissues.

Medication

In some situations, when surgery and radiation don't produce a normalisation of cortisol production, your doctor may advise drug therapy. Medication to control excessive production of cortisol includes ketoconazole (Nizoral®), mitotane (Lysodren®) and metyrapone (Metopirone®). Medication is sometimes prescribed before surgery for people who are very ill. The medication may improve the signs and symptoms and minimise their surgical risk.

In some cases, the tumour or its treatment will cause other hormones produced by the pituitary or adrenal gland to become deficient (inadequate) and your doctor will recommend hormone replacement medication.

If none of these treatment options are effective, your doctor may recommend surgical removal of your adrenal glands (bilateral adrenalectomy). This procedure will cure excess production of cortisol. However, your ACTH levels will remain high, possibly causing excess pigmentation of your skin.

If left untreated, the symptoms of Cushing's syndrome may become more severe and may ultimately lead to death. However, most often, treatment improve signs and symptoms and normalise cortisol levels.

References

1. AMERICAN FAMILY PHYSICIAN. 1 September 2000.

2. UpToDate Inc