Cushing's disease

Cushing's disease is the collection of clinical symptoms and signs resulting from a pituitary tumour that causes excessive amounts of the hormone cortisol to be released by the adrenal glands.

Alternative names for Cushing’s disease

Cushing disease

What is Cushing’s disease?

Cushing’s disease is the collection of symptoms and signs resulting from prolonged exposure to high levels of cortisol. In Cushing’s disease, the cause of the excessive cortisol relates to a benign tumour of the pituitary gland.

What causes Cushing’s disease?

Cushing’s disease is caused by a tumour in the pituitary gland. This tumour produces high levels of a hormone called adrenocorticotropic hormone which, in turn, causes the adrenal glands to produce excessive amounts of the hormone, cortisol.

In most cases, the cause of the tumour cannot be identified. In a small number of cases, the pituitary tumour that causes Cushing’s disease is part of an inherited condition known as multiple endocrine neoplasia type 1.

What are the signs and symptoms of Cushing’s disease?

The signs and symptoms are weight gain (particularly around the midriff), puffiness of the face with a characteristic ‘flushed’ appearance, reduction in sex drive, irregular periods, thinning and bruising of the skin, stretch marks (particularly in the abdomen), muscle weakness (with wasting of the muscles in the arms and legs), excessive hair growth, high blood pressure, high blood sugar (diabetes mellitus or sugar diabetes) and thinning of the bones (osteoporosis). In children, Cushing’s disease leads to weight gain and a reduction in a child’s rate of growth. It can also delay the onset of puberty.

How common is Cushing’s disease?

Cushing’s disease is very rare. One to two new patients per million are diagnosed each year, which means approximately 60–120 new cases per year in the UK. It is more common in women and occasionally occurs in children.

Is Cushing’s disease inherited?

Cushing’s disease is generally not inherited. The exception is in people who have multiple endocrine neoplasia type 1, who may well inherit this condition from a parent.

How is Cushing’s disease diagnosed?

Outpatient tests include:

  • a urine collection, which is taken to measure cortisol levels; patients are asked to collect urine over a 24-hour period
  • dexamethasone suppression tests. Patients are asked to take dexamethasone, a steroid tablet, followed by a blood test. They may be asked to take a single dose of 1 mg at 11 p.m. – 12 midnight, then to return for a blood test at 9 a.m. the next morning (the overnight dexamethasone suppression test). The more formal ‘low dose dexamethasone suppression test’ requires the individual to take eight doses of 0.5 mg consecutively at 9 a.m., 3 p.m., 9 p.m. and 3 a.m. for a period of 48 hours before returning for a blood test
  • cortisol tests at 12 midnight – this may either be done as a blood test (as an inpatient) or as an outpatient (which involves collection of saliva in a special tube)
  • scanning of the pituitary gland using a magnetic resonance imaging (MRI) machine.

Inpatient tests include inferior petrosal sinus sampling. This involves placing thin plastic tubes, under local anaesthetic, into a vein in the groin area. These are threaded into the blood vessels next to the pituitary gland with the aid of an X-ray machine and are used to take blood samples to confirm that there are excessive levels of adrenocorticotropic hormone coming from the pituitary gland.

How is Cushing’s disease treated?

There are a number of different treatments for Cushing’s disease:

  1. Surgical removal of the pituitary tumour causing Cushing’s disease. This is performed at specialist neurosurgical hospitals. The surgery is usually done through the nose and leaves no visible scars. This is usually successful in up to 80% of patients.
  2. Surgical removal of the adrenal glands. This is performed at specialist hospitals. This operation is usually performed only if there is a particular reason for the pituitary tumour itself not being removed or if pituitary surgery has been unsuccessful in curing the disease. Adrenal removal can be done laparoscopically, that is, through small cuts in the skin.
  3. Tablets to reduce the amount of cortisol made by the adrenals. Examples of these medications are metyrapone and ketoconazole. Usually these are given only for a short time in order to prepare patients for surgery.
  4. Radiotherapy to the pituitary. This is usually an outpatient therapy and is given when the patient is unable to have surgery. It is also sometimes given if pituitary surgery is unsuccessful in curing the disease. This treatment involves making a custom-fitted mask to allow the head to be positioned precisely under the radiotherapy machine. The treatment is given over a period of four to five weeks in small, daily doses.

Are there any side-effects to the treatment?

The possible side-effects of surgery include excessive bleeding, infections and pain. After successful surgery to cure the Cushing’s disease, it is necessary for the cortisol hormone to be replaced. This is given as hydrocortisone tablets, taken two to three times a day. These may only be needed for a few months before normal pituitary and adrenal function returns, but occasionally have to be continued indefinitely.

Surgery of the pituitary gland may cause the other hormones made by the pituitary gland to fall in level and it may be necessary to replace these vital hormones in tablet or injection form.

Cortisol-reducing tablet treatments may affect the liver and, therefore, liver blood tests are checked in order to ensure there are no serious problems.

What are the longer-term implications of Cushing’s disease?

It is important that control of raised cortisol is achieved in order to prevent adverse health effects (such as increased cardiovascular disease). Once the disease is cured, the changes due to excessive cortisol production will return to normal over the following weeks or months. The patient’s appearance will return, often rapidly, to normal, and muscle and bone strength will also improve although some patients, particularly post-menopausal women, may need treatment for osteoporosis.

Blood pressure and blood sugar will need to be watched and, if they remain raised, may need to be treated as in any other patient.

If the Cushing’s disease is cured, patients may need to continue taking hydrocortisone replacement tablets for life. As the body is unable to make its own cortisol in response to stressful situations such as illness, surgery and injury to the body, increased doses of hydrocortisone must be supplied in such situations to ensure that the body is able to cope.

Even once in remission, patients who have had Cushing’s disease for a prolonged period of time may have thin bones (osteoporosis) and weak muscles. Weight-bearing activity is important to improve both muscle and bone strength. If osteoporosis is present, this may require further medication to improve the strength of the bones.

Even for patients who are considered to be cured, long-term follow-up with a specialist (endocrinologist) is required as there is a chance of relapse. Patients should discuss any concerns with a medical professional.

Last reviewed: Nov 2020