Hypercortisolism; Cushing syndrome
Cushing’s syndrome is the name of a disorder that occurs when the body is exposed to an excess of steroids such as the hormone cortisol or similar synthetic versions. This can occur either because:
Cortisol is a steroid hormone produced by the adrenal glands, which sit on top of the kidneys. The adrenal glands are stimulated by a pituitary hormone called adrenocorticotropic hormone to release cortisol into the bloodstream.
There are a number of causes of Cushing’s syndrome:
Cushing’s syndrome is characterised by the following signs and symptoms:
The most common form of Cushing’s syndrome is the exogenous form, i.e. due to the patient taking an excess of steroid medication. Endogenous Cushing’s syndrome is rarer and is estimated to affect 1 in 500,000 adults per year. Of these, 85% have pituitary-dependent Cushing’s syndrome, 10% have adrenal Cushing’s and 5% have ectopic adrenocorticotropic hormone production (from a non-pituitary tumour).
Cushing’s syndrome is not usually inherited, but in very rare cases can run in families.
The first step in diagnosing Cushing’s syndrome is to look at current medication the patient is taking to rule out exogenous Cushing’s syndrome. Steroids can be found in prescription medications such as tablets, creams, ointments, inhalers, drops or sprays. Occasionally, steroids may be found as a contaminant in certain herbal preparations.
To diagnose endogenous Cushing’s syndrome, excessive cortisol levels can be measured in blood and urine samples taken over a 24-hour period. Usually, cortisol levels fall at night, but in patients with Cushing’s syndrome cortisol levels remain high.
The overnight dexamethasone suppression test is routinely used to screen for Cushing’s syndrome. In this test, the patient takes 1 mg of a synthetic steroid called dexamethasone at midnight then has a blood test for cortisol at 9 a.m. the next morning. In patients without Cushing’s syndrome, cortisol levels are reduced, but in patients with Cushing’s syndrome cortisol levels will remain raised. This screening test is then followed by a low dose dexamethasone suppression test to confirm the diagnosis.
Once Cushing’s syndrome is confirmed, further blood tests may then be carried out, possibly as an inpatient, as well as specialised computerised tomography (CT) scans of the adrenal glands or magnetic resonance imaging (MRI) scans of the pituitary (depending on the results of the blood tests). This will establish whether the excess cortisol is due to a problem with the adrenal glands or whether excess adrenocorticotropic hormone is driving the adrenals to produce too much cortisol.
Inferior petrosal sinus sampling may be carried out to determine whether the source of the adrenocorticotropic hormone production is within the pituitary gland. 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. The blood samples will help distinguish Cushing’s disease from ectopic adrenocorticotropic hormone production.
A bone mineral density test may also be carried out to test for osteoporosis.
It may take some time before investigations are complete and Cushing’s syndrome is diagnosed.
Exogenous Cushing’s syndrome is treated by gradually reducing the steroid drug dose under medical supervision, if this is possible. This must be done in conjunction with the specialist who prescribed the steroid drug. In some serious conditions, the steroids cannot be stopped. For some conditions, there are alternative drugs to steroids, but these might have their own side-effects. It is very important that the patient does not stop taking any steroid medication without discussing it with their doctor.
Depending on the cause, endogenous Cushing’s syndrome is treated by surgery, medication, or radiotherapy. Patients should be treated in a specialist centre with dedicated endocrinologists and surgeons working in a multidisciplinary team. The main goals of treatment are to bring cortisol levels back to normal, to reverse signs and symptoms and to maintain control in the long term.
After treatment, it is often necessary for the patient to take hydrocortisone tablets to replace the cortisol hormone, as usual cortisol production is often suppressed after successful treatment. Patients would become very unwell if this treatment is stopped without ensuring that production of cortisol has returned. Hydrocortisone tablets are taken two to three times a day until normal pituitary and adrenal function is restored. This could be for several months or patients may need to continue taking hydrocortisone for life.
If pituitary surgery or radiotherapy is carried out, the patient may develop deficiencies of other hormones which may need replacement (hypopituitarism). It may be necessary for the patient to take tablets for life to replace these essential pituitary hormones.
Tablets taken to reduce cortisol levels can have side-effects on the liver and kidneys, so regular blood tests are carried out to make sure the patient is on the correct dose and that there are no serious problems.
Following successful treatment of Cushing’s syndrome, it may take between several weeks and a couple of years for the changes due to excessive cortisol production to return to normal and for the symptoms to disappear. Muscle and bone strength will improve, but some patients, particularly post-menopausal women, may need treatment for osteoporosis. Blood pressure and blood sugar should be closely monitored.
Patients may need to take hydrocortisone replacement tablets for life. Higher doses of hydrocortisone must be supplied for medical emergencies as the body is unable to make its own cortisol in response to stressful situations. Patients should also carry an intramuscular hydrocortisone injection in case of vomiting and a steroid card, and wear Medic-Alert jewellery.
Last reviewed: Feb 2018