What causes Cushing’s syndrome?
The most common cause of Cushing’s syndrome is the use of medication that contains cortisol.
In the case of endogenous Cushing, Cushing’s disease is caused by a pituitary tumour (usually benign) in around 70% of cases. Cortisol-producing adrenal tumours (whether benign or malignant) and ectopic ACTH-producing tumours (again, whether benign or malignant) occur less frequently (in 10 to 15% of cases). Ectopic production of CRH is very rare. Cushing’s disease can also form part of a genetic syndrome.
How frequently does Cushing’s syndrome occur?
The most common cause of Cushing’s syndrome is the use of medication that contains cortisol or substances that resemble cortisol, but it is not clear how frequently this form of Cushing actually occurs. It is estimated that there are approximately 50 newly diagnosed cases of Cushing in the Netherlands each year.
What are the consequences of Cushing’s syndrome?
Too much cortisol can give rise to all kinds of signs and symptoms. Examples are:
- A typical distribution of fat: build-up of fatty tissue around the abdomen (central obesity) and the neck (buffalo hump)
- Loss of muscle tone, resulting in thin arms and legs and reduced muscle power
- Increase in weight
- A round and bloated face (moon face) with blushed cheeks
- High blood pressure
- Excess blood-sugar levels (diabetes)
- Acne of the skin
- Thin and fragile skin, which bruises more easily than normal
- ‘Stretch marks’ (striae) across the abdomen and buttocks
- Sleep problems
- Memory and concentration problems
- For women: menstruation problems and reduced fertility
- Brittle bones (reduced bone density)
- Mood swings, such as depression, euphoria or a psychosis
The quality of life for people with Cushing’s syndrome is often reduced. In addition, they have a greater chance of developing cardiovascular disorders. Despite treatment, the symptoms can sometimes persist. It is impossible to predict which symptoms this will be, or how severe they will be; everyone is different. After treatment, the body has to get used to going without the high levels of cortisol that were once present.
How is Cushing’s syndrome diagnosed?
First of all, it is necessary to check whether the person in question is taking any medication that contains cortisol or substances resembling cortisol. This is, after all, the most common cause of Cushing’s syndrome, and in that case efforts will be made to reduce the medication. After a while, Cushing’s syndrome will fade away.
If the person is not taking any medication of this type, tests will be done to measure the level of cortisol in the body. This investigation can be very difficult. There are many factors that can affect the level of cortisol in the blood, including poorly medicated diabetes, excessive consumption of alcohol, and obesity. Quite often, multiple tests have to be carried out and, if necessary, repeated.
The most commonly used test is the overnight dexamethasone suppression test. At 11 p.m., 1 mg of dexamethasone medication is taken; this will suppress the production of cortisol by the adrenal glands. Next morning, between 8 and 9 a.m., a blood test will measure the amount of cortisol in the blood. If the level has not reduced enough after taking the dexamethasone the night before, this means that there is too much cortisol in the blood. This condition is also known as ‘hypercortisolism’. The level of cortisol can also be determined by measuring the cortisol in urine collected over a 24 hour period, or from a saliva swab taken late in the evening at around 11 p.m. If the cortisol in the urine or saliva is too high, this is a sign of hypercortisolism. Sometimes the cortisol concentration in the blood will be measured at different times of the day. The highest level is normally found in the morning, and it reduces gradually over the course of the day. In the case of Cushing’s syndrome, this normal daytime rhythm is not present.
If hypercortisolism is found, further tests will be carried out to discover the underlying cause of Cushing’s syndrome. The level of the hormone ACTH is measured in the blood. If the ACTH is (too) low, Cushing’s syndrome is being caused by a tumour in the adrenal gland. A CT will then be taken of the adrenal glands to look for a tumour that might be producing the cortisol. If the ACTH is normal or slightly raised, this could be a case of Cushing’s disease or ectopic Cushing. Sometimes it is necessary to carry out additional tests to distinguish between Cushing’s disease and ectopic Cushing. Examples of such tests are the high-dosage dexamethasone suppression test, a CRH test, or a special test whereby blood from the area around the pituitary gland is tested (this is known as petrosal sinus sampling). Sampling means ‘collecting’, in this case collecting a sample of blood. An MRI scan of the pituitary gland can reveal a pituitary tumour. In the case of ectopic Cushing, a CT scan can be taken of the chest and abdominal organs, or a nuclear scan can be carried out.
How is Cushing’s syndrome treated?
Treatment depends on the underlying cause, but usually consists of an operation to remove whatever is causing the overproduction of cortisol. Prior to the operation, the patient is usually given pre-operative treatment with medication to reduce the high levels of cortisol in the body. In the case of Cushing’s disease, the preferred treatment is to remove the tumour in the pituitary gland (transphenoidal resection, an operation through the nose). This operation is only carried out by the most experienced neurosurgeons. If surgery does not have sufficient effect, supplementary treatment will be necessary; this might be another operation, radiotherapy or treatment with medication to neutralise the high levels of cortisol in the blood.
In the case of Cushing’s syndrome caused by an adrenal gland tumour, the preferred treatment is to surgically remove the tumour. This is usually carried out as keyhole surgery (laparoscopy), as long as the tumour is not too large. If it is, it is removed in a normal operation.
In the case of ectopic Cushing, the aim of treatment is to surgically remove the tissue that is producing ACTH or CRH.
If the root cause of Cushing cannot be removed, treatment consists of medication to neutralise the high levels of cortisol in the blood. Another option is to remove both adrenal glands.