How is Cushing’s syndrome treated?

The treatment for Cushing’s syndrome depends on the cause

Cushing’s syndrome is generally caused by either:

A tumor that is causing overproduction of cortisol, which is a glucocorticoid (a steroid hormone) produced in the adrenal glands. Doctors call this an endogenous (inside the body) cause.1,2

or

A medicine, specifically a glucocorticoid-containing medicine such as hydrocortisone, that is adding more glucocorticoid to the body than it can handle. Doctors call this an exogenous (outside the body) cause.1,2 Click here for more information.

If Cushing’s syndrome is caused by a glucocorticoid-containing medicine, then the treatment is to gradually stop taking the medicine. This is done only under a doctor’s supervision.

If Cushing’s syndrome is caused by a tumor, there are several treatment options. These include the following:

Surgery for Cushing’s syndrome

Surgery to remove the tumor is considered the most effective way to treat Cushing’s syndrome, though in some children, radiation therapy may be used (see below).¹

Surgery can frequently cure Cushing’s syndrome. However, it usually takes time for signs and symptoms to get better. For some people, surgery may not prove effective. In those cases, additional treatment is needed.¹

Pituitary surgery^1,3

Pituitary tumors, the most common tumors causing Cushing’s syndrome, are typically benign (noncancerous). When Cushing’s syndrome is caused by a pituitary tumor, it is called Cushing’s disease.^1,3

Transsphenoidal surgery is the type of surgery most often used to remove pituitary tumors. During this procedure a neurosurgeon, who should be skilled and experienced in this type of surgery, reaches the pituitary gland through an incision in the mouth or nose.^4-6

Pituitary tumors can sometimes be so small that they are not detected using imaging tests. In those cases, exploratory surgery may be used to locate the tumors.⁴

Success rates are higher and recurrence rates are lower if the pituitary tumor is removed when it is small. For example, success rates are as high as 90% for small tumors, but less than 65% for large tumors. Success is considered the effectiveness of the treatment in reducing cortisol levels.⁴

Adrenal surgery¹

Adrenal surgery is performed to reduce excess cortisol levels when either¹:

• There is a benign or malignant tumor in the adrenal gland. In this case, the adrenal gland containing the tumor is removed. Adrenal tumors cause Cushing’s syndrome in only a small number of cases
• An ACTH-producing tumor is causing excess cortisol production, but the tumor cannot be located. In this case, both adrenal glands are removed, which permanently stops cortisol production

Though removing both adrenal glands can cure Cushing’s syndrome, all treatment options should be considered first, because patients who undergo this surgery will have to take glucocorticoid medicine for the rest of their lives. In addition, they are at risk of developing Nelson’s syndrome, a condition in which a tumor that was already in the pituitary gland will grow aggressively and produce a large amount of ACTH, which causes excess skin pigmentation.^1,6

A procedure called laparoscopic surgery can be used to remove one or both adrenal glands.¹ This type of surgery—which uses a fiber optic viewing tool placed through an abdominal incision—is less invasive than traditional surgery.

Radiation therapy for Cushing’s syndrome

Radiation therapy at the pituitary gland can be used if transsphenoidal surgery is ineffective. It may have a good success rate in these cases, from 45% to 83%.^7,8 Radiation therapy can also be used as the first treatment for children with Cushing’s syndrome. In one study, the success rate was high at 85%.⁷ However, radiation therapy can cause a condition called hypopituitarism,^1,6 which means that the pituitary gland partially or completely stops working.

It is important to know that it can take a long time after radiation therapy before there is any real improvement.

Medicines for Cushing’s syndrome

Currently, there are no medicines that have been approved specifically to treat Cushing’s syndrome or reduce ACTH. However, medicines to reduce cortisol production may be used in the following situations⁶:

Before surgery if …

• The doctor wants to reduce the level of cortisol circulating in the body. This helps the body adjust while waiting for surgery

Instead of surgery if …

• A person is unable to undergo surgery
• The source of Cushing’s syndrome is unknown

After surgery if …

• Surgery wasn’t successful (that is, if Cushing’s syndrome is still present or comes back)

After radiation therapy until …

• Patients start to feel the benefits of radiation therapy

Following are some medicines that can reduce cortisol levels in people with Cushing’s syndrome. However, these medicines provide limited results over the long term, and if they are discontinued, cortisol levels will usually go up again.^8,9

Ketoconazole^8,10

How it helps:

• Can quickly reduce cortisol levels
• Can stop diabetes and high blood pressure caused by Cushing’s syndrome
• Can lower cholesterol

How often it’s taken:

• Up to 4 times a day

Considerations:

• Can cause liver problems and gastrointestinal upset, and the risk of serious liver toxicity increases the longer it’s taken¹¹
• Can reduce sex drive in men

Metyrapone^8,10

How it helps:

• Can quickly reduce cortisol levels

How often it’s taken:

• 3-4 times a day

Considerations:

• Can cause high blood pressure, acne, nausea, and excess hair growth (hirsutism)

Mitotane^8,10

How it helps:

• Can reduce cortisol levels

How often it’s taken:

• Once a day

Considerations:

• Can take weeks to reduce cortisol when given at lower doses
• At higher doses, can cause dizziness, confusion, and other side effects; after continuous long-term use, these side effects can include reversible brain damage and impairment of function¹²
• May also cause nausea, diarrhea, and higher cholesterol

While these and other medicines can reduce cortisol levels, they do not have any effect on pituitary tumors or ACTH levels. These medications are not usually effective as the sole long-term treatment, and are used mainly as an adjunctive treatment with or after surgery, pituitary radiation, or both.¹

Next, find a helpful list of questions to ask your doctor about Cushing’s syndrome.

References: 1. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367:1605-1617. 2. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88:5593-5602. 3. Pathophysiology of disease: disorders of the hypothalamus & pituitary gland. AccessMedicine Web site. http://www.accessmedicine.com/ content.aspx?aID=2090603.Accessed July 30, 2009. 4. Biller BMK, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2008;93:2454-2462. 5. National Institutes of Health. Cushing’s syndrome. NIH Publication No. 08-3007.2008;1-10. 6. Boscaro M, Barzon L, Fallo F, Sonino N. Cushing’s syndrome. Lancet. 2001;357:783-791. 7. Nieman LK, Ilias I. Evaluation and treatment of Cushing’s syndrome. Am J Med. 2005;118:1340-1346. 8. Nieman LK. Medical therapy of Cushing’s disease. Pituitary. 2002;5:77-82.Accessed August 4, 2009. 9. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367:1605-1617. 10. Morris D, Grossman A. The medical management of Cushing’s syndrome. Ann. NY Acad Sci. 2002;970,119-133. 11. Nizoral^® summary of product characteristics. Janssen-Cilag Ltd, High Wycombe, Bucks, UK; 2008. 12. Lysodren^® summary of product characteristics. Laboratoire HRA Pharma, Paris, France; 2009.