What is 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. [1] [2] However, many more people overproduce cortisol and may have milder symptoms of Cushing's syndrome without being diagnosed as such.

Blood pressure

The pressure the blood places on the walls of the arteries, largely mirroring the contraction of the heart, and consisting of two readings. The higher reading is systolic blood pressure, when the heart contracts, and the lower is diastolic blood pressure, when the heart is relaxed.

Glucose

A simple sugar found in many foods (such as fruit) that functions as a major energy source for the body.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

Inflammation

A body’s protective immune response to injury or infection. The accumulation of fluid, cells and proteins at the site of an infection or physical injury, resulting in swelling, heat, redness, pain and loss of function.

Protein

1. One of the three macronutrients in foods that supply the body with energy. Food rich in proteins include meats, legumes and dairy foods. 2. Large molecules, such as antibodies and albumin, that are found in the blood.

Cortisol

1. A chemical produced by the adrenal glands that is involved in stress responses, maintaining blood sugar levels and helping the immune system. 2. A steroid hormone that can be used to treat inflammation, especially of the skin and joints.

1. Newell-Price, J. (2010). Etiologies of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.

2. Stratakis, C.A. (2012). Cushing Syndrome in Pediatrics. Endocrinology and Metabolism Clinics of North America 41: 793–803.

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.

The hormone cortisol.ACTH and cortisol production. 

Pituitary adenoma

This is responsible for about 70% of cases of Cushing's syndrome. [3]   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. [4] 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. [5]

Adrenal gland

Two glands, each located on top of a kidney, that produce hormones including cortisol and sex hormones.

Benign

Not leading to cancerous growth. Not harmful.

Carcinoma

Cancer of the tissues lining the internal organs, body cavities, surfaces and tubes.

Fetal

Relating to an an unborn baby.

Glucocorticoids

A class of drugs that reduce inflammation, commonly used in the treatment of asthma, arthritis and allergic skin conditions. Cortisone is a glucocorticoid.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

Tumor

A growth caused by an abnormal and uncontrolled reproduction of cells.

Cancerous

Pertaining to cancer, a disease characterized by growth of abnormal cells that can spread to other parts of the body.

Hormonal

Relating to hormones, which are chemicals secreted in one part of an organism and transported to another part of that organism, where they have a specific effect.

Cortisol

1. A chemical produced by the adrenal glands that is involved in stress responses, maintaining blood sugar levels and helping the immune system. 2. A steroid hormone that can be used to treat inflammation, especially of the skin and joints.

3. Biller, B.M.K., Swearingen, B. & Tritos, N.A. (2011). Management of Cushing disease. Nature Reviews Endocrinology 7: 279+.

4. McCune-Albright syndrome. (2014, October 9). Genetics Home Reference. Accessed 17 October 2014, from

External link

5. Manipadam, M.T., Abraham, R., Sen, S., et al. (2011). Primary pigmented nodular adrenocortical disease. Journal of Indian Association of Pediatric Surgeons 16: 160–162.

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: [6]

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.

Anxiety

A feeling of tension, nervousness and dread about future events. It can trigger physical symptoms such as a rapid pulse or breathing difficulties.

Atrophy

Tissue wasting away; reduction in size of tissue in the body.

Blood pressure

The pressure the blood places on the walls of the arteries, largely mirroring the contraction of the heart, and consisting of two readings. The higher reading is systolic blood pressure, when the heart contracts, and the lower is diastolic blood pressure, when the heart is relaxed.

Diabetes

A metabolic disorder that is caused by problems with insulin secretion and regulation and which is characterized by high blood sugar levels. Also known as diabetes mellitus.

Fatigue

A state of exhaustion and weakness.

Fertility

The ability to conceive a baby.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

Vertebrae

The bones that make up the spinal column.

Cortisol

1. A chemical produced by the adrenal glands that is involved in stress responses, maintaining blood sugar levels and helping the immune system. 2. A steroid hormone that can be used to treat inflammation, especially of the skin and joints.

Metabolic syndrome

The combination of abdominal obesity, high blood-sugar level, abnormal cholesterol level and high blood pressure that is associated with an increased risk of developing type 2 diabetes, heart disease and stroke.

6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.

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.

Blood tests

During a blood test, blood can be drawn using a needle or by a finger prick. Your blood can then be analyzed to help diagnose and monitor a wide range of health conditions.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

MRI

A type of imaging that uses a magnetic field and low-energy radio waves, instead of X-rays, to obtain images of organs.

Urine tests

A routine examination of the urine for cells, microbes, or chemicals that can indicate a range of different illnesses.

6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.

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.

Chemotherapy

A medication-based treatment, usually used in the treatment of cancers. There are numerous, different types of chemotherapy drugs that can be prescribed by a specialist. These can commonly be used alongside other cancer treatments such as surgery and radiotherapy.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

Radiotherapy

A treatment that uses ionizing radiation to kill or control growth of malignant cancer cells.

Cortisol

1. A chemical produced by the adrenal glands that is involved in stress responses, maintaining blood sugar levels and helping the immune system. 2. A steroid hormone that can be used to treat inflammation, especially of the skin and joints.

6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.

Potential complications and prognosis

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

Anxiety

A feeling of tension, nervousness and dread about future events. It can trigger physical symptoms such as a rapid pulse or breathing difficulties.

Blood pressure

The pressure the blood places on the walls of the arteries, largely mirroring the contraction of the heart, and consisting of two readings. The higher reading is systolic blood pressure, when the heart contracts, and the lower is diastolic blood pressure, when the heart is relaxed.

Heart disease

A class of diseases that involves the dysfunction of the heart and/or the blood vessels.

Cholesterol

A type of fat produced by the body that is necessary for metabolism.

Circulation

Moving in a circular route, as in blood through the body.

Fatigue

A state of exhaustion and weakness.

Kidney

A pair of organs responsible primarily for regulating the water balance in the body and filtering the blood.

Protein

1. One of the three macronutrients in foods that supply the body with energy. Food rich in proteins include meats, legumes and dairy foods. 2. Large molecules, such as antibodies and albumin, that are found in the blood.

Manic

Relating to mania, which is the mood of feeling abnormally excited.

6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.

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.

6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.