Cushing's syndrome

Cushing's syndrome is an endocrine disorder caused by a high level of cortisol hormone or other types of corticosteroids in the blood.

Cortisol is a type of corticosteroid produced by the adrenal glands. Cortisol regulates blood sugar level, is involved in the metabolism of fats and proteins, and has a controlling effect on salt and water balance of the body.

The adrenal glands, also known as suprarenal glands, are two small triangular-shaped glands located just above the kidneys. They produce and secrete hormones that are essential for the body.

The production of cortisol is controlled by the adrenocorticotropic hormone (ACTH). This hormone is produced by the pituitary gland or hypophysis (located at the base of the brain).

Cortisol level is highest in the morning when you wake up and decline as the day progresses.

A high level of cortisol in the blood may result from several causes:

• Endogenous (occurring within the body):
  • Adrenocorticotropic hormone (ACTH) dependent – 75% of the endogenous cases:
    • Pituitary adenomas (noncancerous or benign tumors in the pituitary gland): This is known as Cushing's disease, which is a bit different from Cushing's syndrome.
    • Tumors in other areas (ectopic Cushing's syndrome or ectopic ACTH syndrome):
      • Small cell lung cancer (the most common)
      • Thymic tumor
      • Pancreatic cancer
      • Thyroid cancer
      • Tumor of the adrenal glands
      • Pheochromocytoma and paraganglioma
  • Adrenocorticotropic hormone (ACTH) independent or adrenal Cushing's syndrome – 25% of the endogenous cases:
    • Adrenal tumors
    • Adrenal hyperplasia
• Exogenous (due to external causes):
  It is the most common cause in general that lead to Cushing's syndrome. It is usually due to the administration of drugs, such as corticosteroids or glucocorticoids (prednisone, dexamethasone, or prednisolone) or due to high doses of Megestrol (a synthetic female hormone).

Some genetic diseases such as McCune-Albright syndrome or Li-Fraumeni syndrome can also cause Cushing's syndrome.

It is estimated that Cushing's syndrome has an incidence of 1 to 3 cases out of every one million people per year.

Cushing's syndrome is more frequent in females with a female-to-male ratio of 3 to 1. It usually strikes adults between the ages of 20 and 50. It rarely affects children.

People who suffer from Cushing's disease usually have a particular physical appearance:

• Moon face (round, red and swollen)
• Thin arms and legs
• Fine fingers
• Truncal obesity (excessive abdominal fat around the stomach and abdomen)

One of the main symptoms of Cushing's syndrome is fragile small blood vessels that leads to:

• Easy or frequent bleeding
• Nosebleeds (epistaxis)
• Easy bruising and stretch marks on the abdomen, buttocks, thighs and breasts.

In addition, there may be other symptoms related such as:

• High blood pressure
• Kidney stones (nephrolithiasis or urolithiasis)
• Glucose intolerance
• Osteoporosis
• Abnormal hair growth in women (hirsutism)
• Irregular menstrual periods in women
• Slow growth in children

People with Cushing's syndrome often have an abnormally high cortisol level in the blood.

The most common tests for the diagnosis of Cushing's syndrome are:

• Dexamethasone suppression test: Dexamethasone is administered at night (11 PM) and cortisol level is checked in the morning (8 AM). In healthy people, there is a decrease in the cortisol level. Those affected by Cushing's syndrome show, by contrast, no decrease in the cortisol level.
• Cortisol 24-hour urine test (24-hour free cortisol test): It measures the amount of cortisol that is present in the urine within 24 hours. The excess of cortisol in the blood is processed by the kidneys and excreted into the urine. Those suffering from Cushing's syndrome have a higher amount of cortisol in urine than a healthy one.
• Corticotropin-releasing hormone (CRH) stimulation test: It helps to discern whether the cause of Cushing's syndrome is a pituitary adenoma or may be due to other causes such as an ectopic Cushing's syndrome or an adrenal tumor.

The treatment depends on the the type of problem causing the cortisol excess.

Anyway, there are several drugs to inhibit the excessive cortisol secretion such as metyrapone, ketoconazole, mitotane, trilostane, aminoglutethimide, mifepristone, or etomidate.

If the Cushing's syndrome is due to medication, for example, due to a therapy with corticosteroids, it is advisable to stop taking the medication or lower the dose if possible.

If Cushing's syndrome is caused by a pituitary adenoma or an adrenal tumor, the best treatment is a surgery resection of the tumor.

The prognosis mainly depends on the source of the problem. If it is caused by a pituitary adenoma, about 80% of patients are cured by surgery. If the cause is another type of cancer, the prognosis depends on the extent of the tumor.