Cushing's syndrome

Cushing's syndrome is a rare condition that results from the body being exposed to too much of the hormone cortisol. This hormone is produced by the adrenal glands, and has many important roles in the human body; it regulates blood glucose (sugar), fat, carbohydrate and protein levels, inflammation, blood pressure, bone growth and mood. An excess of it can have unwanted effects.

About 1-2 people in every million have Cushing's syndrome. However, many more people overproduce cortisol and may have milder symptoms of Cushing's syndrome without being diagnosed as such.

Causes

Cushing's syndrome is caused by the body's tissues being exposed to too much cortisol over time. This can be the result of taking glucocorticoid medications, or of the body itself producing too much cortisol.

Medication

Glucocorticoids are substances that mimic the actions of cortisol. They are used by millions of people to treat a wide variety of inflammatory diseases, including lupus, asthma and others.

Overproduction of cortisol

The pituitary gland is a small gland in the brain. It produces the hormone adrenocorticotropin (ACTH), which regulates the production of cortisol from the adrenal glands that sit atop the kidneys. Therefore, problems in the pituitary gland and ACTH will cause problems in the adrenal gland and cortisol production.

ACTH and cortisol production. 

Pituitary adenoma

This is responsible for about 70% of cases of Cushing's syndrome. An adenoma is a type of benign (not cancerous) tumor. The cells in the tumor secrete ACTH, which stimulates cortisol production. When Cushing's syndrome is due to a pituitary adenoma it is called 'Cushing's disease'.

Adrenal tumors

Adrenal tumors are usually benign, although they can be cancerous. The adrenal cells secrete cortisol into the blood.

Ectopic ACTH syndrome

This can be caused by a wide range of tumors (such as a small-cell carcinoma of the lung), which for some reason begin producing ACTH.

Familial Cushing's syndrome

An inherited tendency to develop one of any of the abovementioned tumors.

McCune-Albright syndrome

A rare genetic (but not inherited) disorder that is caused by mutations during early fetal development. This disorder affects the skin, bones and hormonal system. Some people with this disorder can develop Cushing's syndrome.

Primary pigmented micronodular hyperplasia (PPNAD)

PPNAD is a rare genetic cause of Cushing's syndrome. It usually shows up at 10-20 years of age.

Signs and symptoms

Cushing's syndrome is not easy to detect. Because the hormone cortisol is involved in several different biological processes in the body, overexposure to it can cause a wide variety of symptoms. Different people will experience different symptoms at different severities. As a result, people can experience symptoms of Cushing's syndrome for a long time before the diagnosis is made.

Cushing's syndrome can be suspected in people who have:

• High blood pressure that does not respond to treatment;
• Diabetes that does not respond to treatment;
• Metabolic syndrome;
• Polycystic ovary syndrome;
• Osteoporosis, or;
• Depression.

Signs and symptoms of Cushing's syndrome include:

• Fast, unexplained weight gain, usually concentrated in the upper body (central obesity), but thin limbs and buttocks (due to fat loss and muscle atrophy);
• A rounded face ('moon face') and a 'buffalo hump' of fat above the shoulders and around the neck;
• Thin, fragile skin that bruises easily;
• Purple-red lines or strips (striations), especially on the stomach, thighs, shoulders and upper arms;
• Mood changes, irritability, anxiety, memory problems and poor concentration;
• Sleep problems, insomnia;
• Fatigue, weakness;
• Thirst and frequent urination (peeing);
• Excess hair growth in women;
• Menstrual changes - monthly periods become irregular, infrequent or stop completely;
• Difficulty getting pregnant;
• Low libido;
• Erectile dysfunction and decreased fertility in men;
• Slow growth in children, and;
• Bone weakness, leading to bone pain, back pain and other back problems and a higher risk of fractures, especially in spinal vertebrae and ribs.

Methods for diagnosis

Your doctor will diagnose Cushing's syndrome by:

• Asking about your family and medical history, and about any medications you are taking;
• Giving you a physical examination;
• Running laboratory tests, including urine tests, blood tests and measuring hormone levels, and;
• Taking MRI or CT scans of the adrenal glands or pituitary gland, if any tumors are suspected.

The tests are done to rule out other conditions with similar symptoms and to find out what is causing Cushing's syndrome, so that its cause can be treated.

Types of treatment

Treatment of Cushing's syndrome depends on its cause:

Medication regulation

If Cushing's syndrome is a side effect of taking glucocorticoid medication, your doctor may advise adjusting the type or dosage of the medication you are receiving, or taking additional medication to relieve the symptoms (see below).

Surgery

For tumors that are secreting cortisol, surgery can treat the problem. Chemotherapy or radiotherapy can also be used to treat certain tumors.

Cortisol replacement therapy

After surgery, cortisol replacement therapy may be needed, either for short-term or long-term treatment. Even if treatment is effective, it might take weeks until the body's hormone balance stabilizes.

Medication

In cases where surgery is not possible or not enough, medication to block the production or action of cortisol can be used.

Follow-up testing

Even after Cushing's syndrome has been successfully treated, there is a risk that it will return in time. Therefore, people who have been treated for Cushing's syndrome will often have follow-up tests in the following years to check for recurring signs and symptoms.

Potential complications and prognosis

If left untreated, Cushing's syndrome can lead to serious, life-threatening complications, including:

• Heart and circulation problems, especially high blood pressure and dyslipidemia (high blood fats, such as cholesterol in the blood). These are the most dangerous complications faced by people with the syndrome and can increase the chance of heart disease, vascular disease and stroke;
• Bone problems, including osteoporosis and risk of fractures;
• Mood problems including anxiety, depression and, less commonly, manic episodes;
• Memory and concentration problems;
• A higher susceptibility to infections;
• In pregnant women, a higher risk of miscarriage or preterm birth, and;
• Protein breakdown, which can cause muscle wasting, weakness and fatigue, and the greater chance of kidney stones.

Prevention

It is not always possible to prevent Cushing's syndrome. You can lower your risk by being aware of the symptoms, especially if you are taking glucocorticoid medications in the long-term.
If you already have been diagnosed with Cushing's syndrome, you can manage your symptoms by getting enough physical activity, watching your weight and eating a healthy diet.