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Patient education: Cushing's syndrome treatment (Beyond the Basics)

Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD
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The treatment of Cushing's syndrome depends upon the underlying cause. Treatment can reverse most of the symptoms of Cushing's syndrome, although this must be done carefully to minimize the possibility of permanent hormone deficiency and treatment side effects.

This article discusses the treatment of Cushing's syndrome. The causes, symptoms, and diagnosis of Cushing's syndrome are discussed separately (see "Patient education: Cushing's syndrome (Beyond the Basics)"). More detailed information about treatment of Cushing's syndrome is also available. (See "Overview of the treatment of Cushing's syndrome".)


When Cushing's syndrome is caused by glucocorticoids (like prednisone) that are taken for another medical condition (eg, asthma or rheumatoid arthritis), discontinuing the glucocorticoids will resolves symptoms. However, in most cases, the body has adapted to the presence of the glucocorticoids, and they must be tapered off gradually to allow the pituitary and adrenal glands to resume normal function.

Some conditions require prolonged glucocorticoid therapy. In this situation, an alternate plan for managing the signs and symptoms of Cushing's syndrome is necessary.


When Cushing's syndrome results from a corticotropin (ACTH)-producing tumor of the pituitary gland (Cushing's disease), treatment may include surgery, radiation, or medication to lower cortisol levels. (See "Primary therapy of Cushing's disease: Transsphenoidal surgery and pituitary irradiation".)

Surgery — Surgical removal of a small pituitary adenoma (benign tumor) is called transsphenoidal adenomectomy. The pituitary is located at the base of the brain. It is possible to access this area through the gums above the upper front teeth or the nose (figure 1).

Using special instruments, the surgeon makes an incision in one of these areas (figure 2). The incision is extended through the sphenoid sinus, allowing the surgeon to see and remove the adenoma with an endoscope (a thin, lighted tube with a camera). This type of surgery permanently cures Cushing's syndrome in 60 to 70 percent of people.

Sometimes an adenoma cannot be identified; in these cases, some surgeons remove half of the pituitary gland (hemihypophysectomy); other surgeons remove most of the pituitary gland (85 to 90 percent, subtotal hypophysectomy), to be certain that the tumor has been removed.

The downside of removing gland is that it can reduce pituitary function and interfere with ovulation (in women) and sperm production (in men). Lifelong hormone replacement is often necessary after this surgery.

Medical therapy — When pituitary surgery is unable to restore normal cortisol production, several drugs can be used to control cortisol production. Cabergoline, a drug used mostly to treat prolactin-secreting pituitary tumors, can normalize ACTH and cortisol production in approximately 30 percent of patients. Similarly, pasireotide can normalize ACTH and cortisol in 20 to 25 percent of patients with Cushing's disease.

Mifepristone is a medication that can decrease the effects of excess cortisol on glucose, but its role on long-term therapy of Cushing's disease is not well known. Other drugs that block production of cortisol, such as ketoconazole, metyrapone, or mitotane, can also be used to reduce high levels of cortisol while waiting for more definitive treatment.

Radiation — Radiation can be a useful treatment when pituitary tumors cannot be completely removed by surgery. Radiation of pituitary tumors reduces cortisol levels in approximately half of adults and most children with Cushing's disease (pituitary adenoma that makes ACTH). Because this cortisol-lowering effect takes time (3 to 24 months), medications that lower adrenal cortisol production may be given while waiting for the effects of radiation. These medications include ketoconazole and metyrapone.

Adrenalectomy — Surgical removal of the adrenal glands (adrenalectomy) is a final measure that is sometimes recommended if other treatments are not successful. It may be chosen earlier if the patient is extremely ill and the high cortisol levels need to be normalized immediately. Adrenalectomy stops excess cortisol production but requires that you begin lifelong daily glucocorticoid and mineralocorticoid replacement therapy. (See "Patient education: Adrenal insufficiency (Addison's disease) (Beyond the Basics)", section on 'Primary adrenal insufficiency'.)


In some people with corticotropin (ACTH)-producing, nonpituitary tumors found in other parts of the body, surgical removal of the tumor eliminates the symptoms of Cushing's syndrome. These tumors are usually in the lung. When complete surgical removal is not possible, treatment with medications that reduce adrenal cortisol production (ketoconazole and metyrapone) or surgical removal of the adrenal glands (adrenalectomy) may be necessary to lower cortisol levels.


Adrenal tumors are usually treated with surgical removal of the affected adrenal gland, leaving the opposite adrenal gland for cortisol production. If the tumor is an adenoma (a benign tumor), surgery always cures the associated Cushing's syndrome.

If the tumor is a carcinoma (a cancerous tumor), surgery is the only way to cure the cancer; radiation, chemotherapy, and treatment with mitotane (a medication that is toxic to cortisol-producing cells) are usually required to lower cortisol levels (see "Treatment of adrenocortical carcinoma", section on 'Mitotane monotherapy'). After these treatments, daily adrenal hormone replacement is usually necessary. (See "Patient education: Adrenal insufficiency (Addison's disease) (Beyond the Basics)", section on 'Primary adrenal insufficiency'.)


Treatment of nodular adrenal hyperplasia (a very rare disorder) usually requires surgical removal of both adrenal glands. Before surgery, medications that inhibit adrenal enzymes (ketoconazole or metyrapone) can lower cortisol levels.

After surgery, daily adrenal hormone replacement is usually necessary. (See "Patient education: Adrenal insufficiency (Addison's disease) (Beyond the Basics)", section on 'Primary adrenal insufficiency'.)


Cushing's syndrome is rare during pregnancy. The excess cortisol production is usually caused by an adrenal tumor, most often an adenoma (a benign tumor), although some patients have a pituitary tumor (Cushing's disease). (See "Cushing's syndrome in pregnancy".)

Although most of the excess cortisol does not cross the placenta and affect the fetus, untreated Cushing's syndrome poses a risk to pregnant women because it can lead to maternal complications such as high blood pressure and gestational diabetes, and it is associated with miscarriage and premature delivery.

When Cushing's syndrome is caused by an adrenal tumor or a benign pituitary tumor (Cushing's disease), surgical removal of the adrenal or pituitary gland can lower the abnormal cortisol levels without affecting the pregnancy.


If treatment removes the source of excess cortisol, most of the symptoms of Cushing's syndrome disappear within 2 to 12 months. Osteoporosis begins to improve within six months and continues to improve over several years. With successful treatment, children with Cushing's syndrome can regain much of their lost bone density and growth. Some high blood pressure and glucose intolerance may persist. Although symptoms of excess cortisol on the brain (emotional, sleep, memory disturbances) usually improve, some conditions can linger even after cortisol levels have been lowered.


Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Cushing's syndrome (The Basics)
Patient education: Adrenal cancer (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Cushing's syndrome (Beyond the Basics)
Patient education: Adrenal insufficiency (Addison's disease) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Causes and pathophysiology of Cushing's syndrome
Epidemiology and clinical manifestations of Cushing's syndrome
Cushing's syndrome due to primary bilateral macronodular adrenal hyperplasia
Cushing's syndrome in pregnancy
Dexamethasone suppression tests
Establishing the cause of Cushing's syndrome
Establishing the diagnosis of Cushing's syndrome
Overview of the treatment of Cushing's syndrome
Primary therapy of Cushing's disease: Transsphenoidal surgery and pituitary irradiation
Medical therapy of hypercortisolism (Cushing's syndrome)

The following organizations also provide reliable health information.

National Library of Medicine


Hormone Health Network

(www.hormone.org available in English and Spanish)

National Institute of Diabetes and Digestive and Kidney Diseases


National Adrenal Diseases Foundation

(516) 487-4992

Pituitary Tumor Network Association


Cushing's Support & Research Foundation

(617) 723-3674


Literature review current through: Nov 2017. | This topic last updated: Tue Mar 07 00:00:00 GMT 2017.
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