The most common symptoms include a thinning of the skin, weight gain, bruising, high blood pressure, osteoporosis, diabetes, a puffy face, weakness, and, in females, interruption of menstrual periods.

People who are at risk of developing this condition include those who take large doses of steroid medication for another illness, such as asthma, and those with a tumor in the pituitary gland or the adrenal gland. Both of these groups may have too much of the steroid hormone, cortisol.

Causes

Cushing’s syndrome is related to high levels of the hormone cortisol.

The body system that controls hormone production is the endocrine system. Within this system, the glands work together and produce different types of hormones.

These glands include the adrenal glands, pituitary gland, thyroid gland, parathyroid glands, pancreas, ovaries (in females), and testicles (in males).

The adrenal glands are located just above the kidneys, and they produce cortisol. Cortisol is the primary stress hormone, and it is the major natural glucocorticoid (GC) in humans.

Cortisol helps to regulate how the body turns proteins, carbohydrates, and fat from food into energy.

It also helps to control blood pressure and blood glucose levels and to maintain cardiovascular function. It suppresses the immune system, and it affects how the body responds to stress.

When cortisol levels are too high, Cushing’s syndrome can result.

Types

Exogenous Cushing’s syndrome

If the cause comes from outside the body, the condition is called exogenous Cushing’s syndrome.

Exogenous Cushing’s syndrome may be the result of long-term, high-dose usage of corticosteroid drugs, such as Prednisone, dexamethasone, or Decadron, and methylprednisolone, or Medrol.

People with rheumatoid arthritis, lupus, asthma, and recipients of an organ transplant may need fairly high doses of these drugs, in order for their treatment to be effective. This can cause similar effects in the body as excessive cortisol.

Injectable corticosteroids, used for joint pain, back pain and bursitis, can also lead to Cushing’s syndrome.

Steroid creams, such as those used for eczema, are not considered a risk factor for Cushing’s syndrome. Some inhaled steroids, used for asthma, are not linked to a higher incidence of Cushing’s syndrome, except at high doses.

Endogenous Cushing’s syndrome

Endogenous Cushing’s syndrome is when the cause comes from inside the body, for example, the adrenal glands produce too much cortisol.

Sometimes, a tumor can lead to an overproduction of adrenocorticotropic hormone (ACTH), which regulates cortisol production. This could be a benign tumor in the pituitary gland, or a benign or malignant tumor in the pancreas, thyroid, thymus gland or lung.

A disorder of the adrenal glands, such as a non-cancerous tumor, may result in an overproduction of cortisol.

Symptoms

Cushing’s syndrome can affect various parts of the body. Symptoms may vary widely between individual patients, and according to the cause of the disorder.

Weight gain is the hallmark sign of Cushing’s syndrome. High levels of cortisol cause fat to be redistributed, especially to the chest, stomach, and face. A “buffalo hump” may result as fat accumulates on the back of the neck and shoulders.

Children with Cushing’s syndrome may grow more slowly.

Limbs may be thin, compared with the rest of the body, and the face becomes puffy, rounded, and red.

The skin is affected in the following ways:

• It becomes very thin.
• It bruises easily.
• Reddish-purplish stretch marks appear on the stomach, buttocks, limbs, and breasts.
• Spots develop on the shoulders, chest, and face.
• Darkened skin appears around the neck.
• Edema, or water retention, occurs under the skin.
• Skin lesions take a long time to heal, such as grazes, cuts, scratches, and insect bites.

Women may have excessive facial and body hair, known as hirsutism. A woman’s voice may deepen, and she may lose the hair on her head. Menstruation can be disrupted, with periods becoming irregular and less frequent. They may stop completely.

The muscles in the shoulders, limbs, and hips may weaken, and the high levels of cortisol can lead to osteoporosis, or brittle bones. This can make patients more vulnerable to fractures, even during normal daily tasks, such as lifting.

Psychological and mood changes can occur, possibly leading to:

• Anxiety
• Depression
• Irritability
• Loss of emotional control
• Extreme mood swings
• Panic attacks.

Sexual problems include a lower libido, or sex drive, in males. A man may have erectile dysfunction, which is the inability to achieve or sustain an erection, and infertility. However, if the adrenal glands overproduce testosterone and other hormones, this can increase libido.

Other problems include visual disturbances, headaches, hypertension, or high blood pressure, excessively high glucose levels, increased thirst, more frequent urination and profuse sweating.

Anyone who is taking corticosteroid drugs for asthma, arthritis, or inflammatory bowel disease, and who experiences the signs and symptoms of Cushing’s syndrome, should tell their doctor as soon as possible.

Diagnosis

Other conditions and diseases have symptoms similar to those of Cushing’s syndrome, so it is important to eliminate these first.

If a hormonal problem is suspected, the physician will probably refer the patient to an endocrinologist, who may request a urine test, a blood test, or a saliva test, in order to establish the levels of cortisol.

If the patient is diagnosed with Cushing’s syndrome, further tests will be necessary to investigate the cause, which could be a benign or malignant tumor.

While waiting for the results, a patient may be prescribed metyrapone, which blocks the production of cortisol and lowers its concentration in the blood.

Treatment

Treatment aims to reduce cortisol levels, but the type of treatment will depend on several factors, including the cause of the syndrome.

If the cause is corticosteroid use for treatment of asthma, arthritis, or another condition, the physician may reduce the dose of the drug, or replace it with a non-corticosteroid medication.

Patients must not lower corticosteroid dosages without medical supervision, as this could lead to dangerously low levels of cortisol.

A tumor may need surgery. A pituitary tumor may be removed through the patient’s nose. Tumors in the adrenal glands, pancreas or lungs may require conventional surgery or keyhole surgery.

After surgery, patients will need to take cortisol replacement drugs until normal hormone production returns.

Radiotherapy may be used as part of the treatment to remove a tumor, and chemotherapy may be necessary if the tumor is cancerous, for example in the lung.

Drugs such as ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone) can help to control excessive production of cortisol.

If a tumor causes low hormone production, the doctor may prescribe hormone replacement therapy (HRT).