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What causes Cushing’s syndrome?

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Cushing’s syndrome can develop for two reasons:

  • Medication containing a cortisol-like synthetic compound called glucocorticoid 1,2
  • A benign or malignant tumor in the body that makes the adrenal (pronounced uh-DREEN-l) gland produce too much cortisol 1,2

Medication

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:

  • Allergies
  • Asthma
  • Autoimmune (pronounced aw-toh-i-MYOON) diseases, where the body’s immune system attacks its own tissues
  • Organ transplantation, to help avoid organ rejection

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.

Tumors

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

Noncancerous (or Benign, pronounced bih-NAHYN)

  • Pituitary adenoma (pi-TOO-i-ter-ee >ad-n-OH-muh)
  • Adrenal adenoma
  • Adrenal micronodular hyperplasia (pronounced MAHY-kroh-NOJ-uh-ler hahy-per-PLEY-zee-uh)
  • Adenomas in places other than the pituitary or adrenal glands, mostly in the lungs, pancreas, thyroid, or thymus

Cancerous (or Malignant, pronounced muh-LIG-nuhnt)

  • Adrenal cancer
  • Cancer in places other than the pituitary or adrenal glands, mostly in the lungs, pancreas (pronounced PAN-kree-uhs), thyroid, or thymus

How Tumors Can Cause Cushing’s Syndrome

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:

  • A benign pituitary tumor secretes ACTH. This tumor, called a pituitary adenoma, is by far the most common tumor linked to Cushing’s syndrome. As a result, the condition it causes has been given its own name, Cushing’s disease. Pituitary adenomas account for 70% (in adults) to more than 90% (in children) of endogenous (non-medicine-related) Cushing’s syndrome cases.1
  • Adrenal tumors produce cortisol in their tissue, adding to the amount already produced by the adrenal glands. These tumors cause about 15% of endogenous Cushing’s syndrome cases. Children are more likely to have this type of tumor than other tumors, but it is less common in adults. Women are more likely than men to get this type of tumor. These tumors can be adrenal adenomas, micronodular hyperplasia, or cancerous adrenal tumors.
  • Some tumors not in the pituitary or adrenal glands can produce ACTH and force more cortisol production. This condition is sometimes called ectopic (pronounced ek-TOP-ik) Cushing’s disease and accounts for about 15% of non-medicine-related Cushing’s syndrome cases.1 The tumors, either benign or cancerous, are mostly found in the lungs, pancreas, thyroid, and thymus.

Familial Cushing’s Syndrome

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.

Pseudo-Cushing’s Syndrome

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


  1. Nieman L. K., & Ilias, I. (2005). Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340–1346. PMID 16378774. [top]
  2. Mayo Clinic. (n.d.). Case detection of Cushing’s syndrome in adults. Retrieved April 8, 2012, from http://www.mayoclinic.org/medicalprofs/cushing-syndrome.html. External Web Site Policy [top]
  3. Batista, D. L., Courcoutsakis, N., Riar, J., Keil, M. F., & Stratakis, C. A. (2008). Severe obesity confounds the interpretation of low-dose dexamethasone test combined with the administration of ovine corticotrophin-releasing hormone in childhood Cushing syndrome. Journal of Clinical Endocrinology and Metabolism, 93(11), 4323-4330. [top]
  4. Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., et al. (2008). The diagnosis of Cushing’s syndrome: An Endocrine Society clinical practice guideline. Retrieved April 8, 2012, from http://www.endo-society.org/guidelines/final/upload/Cushings_Guideline.pdf External Web Site Policy (PDF - 510 KB). [top]

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Last Updated Date: 11/30/2012
Last Reviewed Date: 11/30/2012
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