Cushing's disease

Cushing's syndrome or hypercortisolism is an endocrine disorder caused by excessive levels of the endogenous corticosteroid hormone cortisol. It may also be induced iatrogenically by treatment with exogenous corticosteroids for other medical conditions.

Cortisol is secreted by the adrenal glands under regulation by the pituitary gland and hypothalamus. Strictly, Cushing's 'Syndrome' refers to excess cortisol of any aetiology whereas Cushing's Disease refers only to hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a tumour in the pituitary gland or, less commonly, elsewhere. About 70% of people provisionally diagnosed with the Syndrome are later found to have the Disease. Therefore, once a definitive diagnosis has been reached, the term Cushing's Syndrome is usually used in those cases where there is primary excess cortisol secretion from autonomous tumours of the adrenal cortex or elsewhere. Identifying the site of the lesion can present diagnostic difficulties.

Symptoms include weight gain, particularly of the trunk and face with sparing of the limbs, 'moon' face, excess sweating, thin and easily bruised skin, purple striae on the trunk and legs, proximal muscle weakness (hips, shoulders), and hirsutism. The excess cortisol may also affect other endocrine axes and cause, for example, reduced libido, impotence, and infertility. Patients frequently suffer various psychological disturbances.

Signs include persistent hypertension (due to the aldosterone-like effects) and impaired ability to regulate glucose. (Cortisol normally increases glucose in the blood, and people with Cushing's are typically hyperglycaemic, and often have frank diabetes).

If an adrenal adenoma is identified it may be removed by surgery. Post-operatively most patients will require steroid replacement at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed replacement with hydrocortisone or prednisolone is imperative.

In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol sythesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy.

In iatrogenic Cushing's, dose adjustment may be sufficient or it may be necessary to change to another type of immunosuppresive medication.

It affects around 15 people in every million.

The converse situation of primary adrenal insufficiency is known as Addison's Disease--which afflicted John F. Kennedy.

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Cushing's syndrome, also known as hypercortisolism, occurs when a person's tissues are exposed to an excess of the hormone cortisol.

When the appropriate amount of cortisol is released by the adrenal glands, it helps regulate blood pressure, energy production, the ability to fight disease, and how the body maintains itself and responds to stress. But too much cortisol can alter the normal function of these processes, resulting in the symptoms of Cushing's syndrome.

Who gets it?

Cushing's syndrome is fairly rare. For every one million people, 2-5 new cases are diagnosed each year, with about 10 percent of these being children and teenagers.

Symptoms

Most children and teenagers with Cushing's syndrome will show several of the following:

• extreme weight gain
• growth retardation
• missed periods in teenage girls
• excess hair growth
• acne
• reddish-blue streaks on the skin
• high blood pressure
• tiredness and weakness
• either very early or late puberty

Adults with the disease may also have symptoms of extreme weight gain, excess hair growth, high blood pressure, and skin problems. In addition, they may show:

• muscle and bone weakness
• moodiness, irritability, or depression
• sleep disturbances
• high blood sugar
• menstrual disorders in women and decreased fertility in men

Causes

Cushing's syndrome can occur when:

• A person takes certain hormones for a long time as treatment for another disorder or disease, for example, taking a steroidal anti-inflammatory for arthritis.
• The body produces too much cortisol. Too much cortisol is produced when the pituitary and adrenal glands are not working properly. This can be caused by:
• A noncancerous tumor of the pituitary gland that produces increased amounts of the hormone adrenocorticotropin (ACTH). This, in turn, prompts the adrenal glands to produce too much cortisol. This form of Cushing's syndrome is known as "Cushing's disease."
• Certain types of cancerous tumors in other parts of the body can produce ACTH, causing the adrenal glands to produce extra cortisol
• Growths on the adrenal glands, that may or may not be cancerous, can cause the adrenal glands to release extra cortisol.

Diagnosis

Doctors review the patient's medical records and do a physical exam. If these suggest Cushing's syndrome, more tests are done. A definite diagnosis involves:

• Seeing if there is too much cortisol in the body, and
• Discovering the cause of extra cortisol. A urine test measures how much cortisol is being produced. If the level indicates Cushing's syndrome, the doctor will order other tests to discover the cause. These may include:
• Biochemistry tests. The dexamethasone suppression test involves taking a man-made cortisol by mouth for several days during which time cortisol levels in the blood and urine are measured. The CRH stimulation test involves receiving an injection of the corticotropin-releasing hormone (CRH) followed by a blood test to see if there is a rise in the levels of ACTH and cortisol.
• Scans. This may include computerized tomography (CT) and magnetic resonance imaging (MRI) scans of the pituitary and adrenal glands, chest, and abdomen; ultrasound imaging of the adrenal glands; chest x-rays; and perhaps a radioisotope procedure called an iodocholesterol scan.
• Catheterization procedures. Samples of the blood leaving the pituitary gland are tested to see if the pituitary is causing the high level of ACTH.

Treatments

If Cushing's syndrome is the result of taking hormones as treatment for another disease, the doctor will adjust the dosage. If Cushing's syndrome is caused by the body producing too much cortisol, treatment may include:

• oral medication (such as metyrapone or ketoconazole).
• radiation to destroy the cells producing excess cortisol.
• surgery to remove a tumor, or
• a combination of treatments. The treatment used will depend on the cause of the extra cortisol.

Cures

Yes! In many cases Cushing's syndrome can be cured. But as with any disease, success is not guaranteed. How effective treatment is depends on the cause and severity of the disease and factors unique to the individual. But even if cure is not achieved, most patients eventually achieve some level of recovery.

Future development

Ongoing research into curing Cushing's syndrome should provide a promising future for individuals with the disease. Doctors can now diagnose Cushing's syndrome with 98 percent accuracy. Researchers are also looking for ways to cure Cushing's syndrome without surgery.