Cushing’s syndrome occurs when the body’s tissues are exposed to high levels of cortisol for too long. Many people develop Cushing’s syndrome because they take glucocorticoids—steroid hormones that are chemically similar to naturally produced cortisol—such as prednisone for asthma, rheumatoid arthritis, lupus, and other inflammatory diseases. Glucocorticoids are also used to suppress the immune system after transplantation to keep the body from rejecting the new organ or tissue.
Other people develop Cushing’s syndrome because their bodies produce too much cortisol. Normally, the production of cortisol follows a precise chain of events. First, the hypothalamus, a part of the brain about the size of a small sugar cube, sends corticotropin-releasing hormone (CRH) to the pituitary gland. CRH causes the pituitary to secrete adrenocorticotropin hormone (ACTH), which stimulates the adrenal glands. When the adrenals, which are located just above the kidneys, receive the ACTH, they respond by releasing cortisol into the bloodstream.
Cortisol performs vital tasks in the body including
The hypothalamus sends CRH to the pituitary, which responds by secreting ACTH. ACTH then causes the adrenals to release cortisol into the bloodstream.
One of cortisol’s most important jobs is to help the body respond to stress. For this reason, women in their last 3 months of pregnancy and highly trained athletes normally have high levels of the hormone. People suffering from depression, alcoholism, malnutrition, or panic disorders also have increased cortisol levels.
When the amount of cortisol in the blood is adequate, the hypothalamus and pituitary release less CRH and ACTH. This process ensures 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 the regulating switches in the pituitary gland or hypothalamus, cortisol production can go awry.
Pituitary adenomas cause 70 percent of Cushing’s syndrome cases, excluding those caused by glucocorticoid use. These benign, or noncancerous, tumors of the pituitary gland secrete extra ACTH. Most people with the disorder have a single adenoma. This form of the syndrome, known as Cushing’s disease, affects women five times more often than men.
Some benign or, more often, cancerous tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause more than half of these cases, and men are affected three times more often than women. The most common forms of ACTH-producing tumors are small cell lung cancer, which accounts for about 13 percent of all lung cancer cases, and carcinoid tumors—small, slow-growing tumors that arise from hormone-producing cells in various parts of the body. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.
In rare cases, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing’s syndrome. Adrenal tumors are four to five times more common in women than men, and the average age of onset is about 40. Most of these cases involve noncancerous tumors of adrenal tissue called adrenal adenomas, which release excess cortisol into the blood.
Adrenocortical carcinomas—adrenal can...
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