Alternative Names: Hypercortisolism, Adrenocortical Hyperfunction.
Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Normally, the production of cortisol follows a precise chain of events. First, the hypothalamus, a part of the brain which is about the size of a small sugar cube, sends corticotropin releasing hormone (CRH) to the pituitary gland. CRH causes the pituitary to secrete ACTH (adrenocorticotropin), a hormone that stimulates the adrenal glands. When the adrenals receive the ACTH, they respond by releasing cortisol into the bloodstream.
When the amount of cortisol in the blood is adequate, the hypothalamus and pituitary release less CRH and ACTH. This ensures that the amount of cortisol released by the adrenal glands is precisely balanced to meet the body's daily needs. However, if something goes wrong with the adrenals or their regulating mechanisms in the pituitary gland or the hypothalamus, cortisol production can become abnormal.
Some patients may have sustained high cortisol levels without the effects of Cushing's syndrome. These high cortisol levels may be compensating for the body's resistance to cortisol's effects. This rare syndrome of cortisol resistance is a genetic condition that causes hypertension and chronic androgen excess.
The most common cause of Cushing's is a tumor in the pituitary gland, and the least common is cancer of the adrenal gland. Many people suffer the symptoms of Cushing's syndrome because they take glucocorticoid hormones – such as prednisone – as an antiinflammatory. Some develop Cushing's syndrome because of overproduction of cortisol by the body.
Other causes include:
Sometimes other conditions may be associated with many of the symptoms of Cushing's syndrome. These include polycystic ovarian syndrome, which may cause menstrual disturbances, weight gain from adolescence, excess hair growth and sometimes impaired insulin action and diabetes. Commonly, weight gain, high blood pressure and abnormal levels of cholesterol and triglycerides in the blood are associated with resistance to insulin action and diabetes; this has been described as the "Metabolic Syndrome-X." Patients with these disorders do not have abnormally elevated cortisol levels.
A 24-Hour urinary free cortisol level is the most specific diagnostic test. Levels higher than 50 to 100mcg per day for an adult suggest Cushing's syndrome. Once Cushing's syndrome has been diagnosed, other tests are used to find the exact location of the abnormality that leads to excess cortisol production. These tests could include dexamethasone suppression test, CRH stimulation test, direct visualization of the endocrine glands (radiologic imaging), petrosal sinus sampling and the dexamethasone-CRH test.