Cushing’s syndrome can develop for two reasons:
Medication is responsible for most cases of Cushing’s syndrome. It is called an exogenous (pronounced ek-SOJ-uh-nuhs) cause because it originates outside the body. Cortisol-like steroid drugs, or glucocorticoids, are by far the main medications linked to Cushing’s syndrome. These medications are used to treat inflammation caused by one of several sources:
Glucocorticoids, such as prednisone (pronounced PRED-nuh-sohn, -zohn), are effective at reducing inflammatory symptoms. However, taking a high dose for a long time can produce Cushing’s syndrome.
Medroxyprogesterone (pronounced mi-drok-see-proh-JES-tuh-rohn) is another drug that occasionally causes Cushing’s syndrome. This progestin medication is taken to treat abnormal menstruation or irregular vaginal bleeding, or to prevent unusual growth of the uterine (womb) lining.
A tumor is an endogenous (en-DOJ-uh-nuhs) cause of Cushing’s syndrome, meaning one that originates within the body. Tumors are a much less common cause of Cushing’s syndrome than are medicines.
The tumors that cause Cushing’s symptoms can be either cancerous or noncancerous.2
Normally, the pituitary gland in the brain controls how much cortisol the two adrenal glands release into the bloodstream. The pituitary gland signals the adrenal glands by releasing adrenocorticotropic (pronounced uh-DREE-noh-kawr-ti-koh-TROP-ik) hormone, also known as ACTH or corticotropin. When the adrenal glands sense the ACTH, they produce more cortisol. But a tumor can disrupt that action. Tumors can either produce extra cortisol directly in their own tissue or produce extra ACTH, which triggers production of more cortisol in turn. This process can happen in three different ways:
Individuals with some rare genetic disorders are more vulnerable to tumors in one or more glands that influence cortisol levels. As a result, these people are more likely to develop Cushing’s syndrome.2 Two such conditions are called multiple endocrine neoplasia type 1 and primary pigmented micronodular adrenal disease.
In rare instances, a person may have symptoms and test results that point to Cushing’s, but further testing reveals that he or she does not have the syndrome. This condition is termed "pseudo-Cushing’s syndrome." Factors that can cause this syndrome are alcohol dependence, depression or other psychiatric disorders, extreme obesity, pregnancy, and poorly controlled diabetes.3,4
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