Cortisol is a corticosteroid hormone made in the adrenal glands, two small organs sitting on top of each kidney. It is produced when the adrenals are stimulated by a hormone produced in the pituitary gland of the brain called adrenocorticotropic hormone (ACTH).
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Cortisol has many important functions throughout the body, ranging from anti-inflammatory effects to maintaining blood pressure and blood sugar. Cortisol levels that are too high produce a number of abnormalities known collectively as Cushing syndrome. Adrenal and pituitary tumors are common causes of high cortisol.
Drug treatment generally includes steroidogenesis inhibitors, neuromodulatory medications or cortisol receptor antagonists. The choice often depends on the cause of the elevated cortisol, as well as possible side effects. If a single medication is not adequate, combinations are often used.
Steroidogenesis inhibitors are a group of medications that directly reduce cortisol production in the adrenal glands. These drugs enter the adrenals to block one or more steps in the cortisol production process. Mitotane (Lysodren), aminoglutethimide (Cytadren), ketoconazole (Nizoral) and metyrapone (Metopirone) are examples of steroidogenesis inhibitors. They are all moderately effective in reducing cortisol levels.
Mitotane commonly causes digestive symptoms. It may also cause decreased memory, other neurologic symptoms, liver dysfunction, high cholesterol, breast growth in men and menstrual abnormalities or ovarian cysts in women. Aminoglutethimide may cause digestive symptoms, drowsiness, weakness, a rash, low blood pressure and low thyroid hormone levels. Ketoconazole, a drug also used to treat fungal infections, can produce liver dysfunction, a rash, digestive symptoms and decreased testosterone levels in men. Metyrapone can cause nausea, facial and body hair growth in women, as well as high blood pressure and low potassium levels.
Neuromodulatory drugs act primarily to decrease the release of ACTH from the pituitary. Bromocriptine (Parlodel), octreotide (Sandostatin), cyproheptadine (Periactin), pasireotide (Signfor) and cabergoline are examples of neuromodulatory drugs that may be used to treat high cortisol levels. The first three are of limited benefit in most patients. Pasireotide and cabergoline, however, are more effective. The most common side effects of pasireotide include digestive symptoms, headaches and elevated blood sugar levels. Cabergoline may cause nausea, low blood pressure, dizziness and psychological changes such as pathologic gambling. Rarely, heart valve problems may occur.
Cortisol Receptor Antagonists
Cortisol receptor antagonists are medications that block the actions of cortisol throughout the body. They do not directly lower cortisol levels. Mifepristone (Korlym, Mifeprex), a drug initially developed as an abortion pill, is the main cortisol receptor antagonist used to treat high cortisol levels. It is generally effective in counteracting the effects of excessive cortisol. But sometimes it can be too effective and cause symptoms of low cortisol, such as weakness and low blood sugar. Other possible side effects include heavy menstrual periods in women, low potassium levels and high blood pressure.
Warnings and Precautions
Most medications for high cortisol levels interact with a number of other drugs, so tell your doctor about all other medications you are taking. Aminoglutethimide, mifepristone, and mitotane should be not used if you are pregnant or might become pregnant. Pasireotide and mifepristone are the only medications that are actually approved by the Food and Drug Administration (FDA) to treat high cortisol levels. The other medications are approved by the FDA, but for other conditions.
Reviewed and revised by Mary D. Daley, MD.
REFERENCES & RESOURCES
- American Family Physician: Cushing's Disease -- Clinical Manifestations and Diagnostic Evaluation
- Johns Hopkins Medicine: Cushing’s Syndrome/Disease
- The Lancet: Cushing’s Syndrome
- Pituitary: Updates on the Role of Adrenal Steroidogenesis Inhibitors in Cushing’s Syndrome -- A Focus on Novel Therapies
- Molecular and Cellular Endocrinology: Current Approaches to the Pharmacological Management of Cushing's Disease
- Endocrine and Metabolism Clinics: Medical Treatment of Cushing Disease -- New Targets, New Hope
- National Institutes of Health: What Are the Treatments for Cushing Syndrome?
- The Journal of Physiology: Cushing's Syndrome: From Physiological Principles to Diagnosis and Clinical Care
- DailyMed: Korlym -- Mifepristone Tablet
- DailyMed: Lysodren -- Mitotane Tablet
- DailyMed: Cabergoline -- Cabergoline Tablet
- National Endocrine and Metabolic Diseases Information Service: Cushing’s Syndrome