Cushing's Syndrome Treatment

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The aim of treatment in Cushing’s syndrome is to relieve the symptoms of the condition by addressing its cause. This may involve adjusting the dose of corticosteroid medications in some cases, if they are regularly used. In other cases, surgery or radiotherapy may be used to remove a tumor that is causing the condition. Pharmacotherapy may also be used to control the level of cortisol in the body and manage the symptoms of Cushing’s syndrome.

Adjusting Pre-existing Corticosteroid Medications

A common cause of Cushing’s syndrome is the chronic use of corticosteroid medications, which alters the concentration of cortisol in the body. For patients with a history of prolonged and constant corticosteroid use, altering the dose of the medication may be sufficient to control the symptoms of Cushing’s syndrome.

In this scenario, it is important that the corticosteroid dose is gradually reduced over several months to maintain adequate control of the inflammatory or other condition which is being treated with the medication, even while reducing symptoms of Cushing’s syndrome. Abrupt cessation of a corticosteroid which has been used for more than a day or two is never advised. This is because the endogenous production of cortisol is often low in such cases.  The low level of cortisol may lead to acute and dangerous deficiency in any period of stress. During the transition period, non-steroidal anti-inflammatory drugs can also be used to bring down the patient’s reliance on the corticosteroid.

Surgical Removal of Tumor

For patients with Cushing’s syndrome linked to the growth of a tumor, surgical removal of the tumor may be required.  

In the case of a pituitary tumor, referral to a neurosurgeon is needed. This is usually done with a procedure known as a trans-sphenoidal adenectomy. This is usually performed under general anesthetic, using an incision through a nostril or upper lip to avoid leaving a facial scar. This requires to be followed by cortisol replacement therapy, usually for a period of 1-2 years, but sometimes for life. It has a success rate of over 80% for tumors of 10 mm diameter or smaller. Larger tumors are successfully treated in this manner approximately 50% of the time. Another option is the use of radiation in weekly doses, for 6 weeks, to ablate the pituitary.

When the reason for Cushing’s syndrome is overproduction by the adrenal glands, minimally invasive surgical techniques such as laparoscopic (keyhole) surgery can be used. In most cases a single adrenal gland is removed. If the high cortisol levels are due to ectopic tumors in the lungs or pancreas, or tumors of the adrenal glands, all the tumor tissue will have to be removed. In such cases, both glands are removed. If the ectopic tissue is too deeply placed in the lung or pancreas, medication to inhibit the effects of cortisol may be required, or bilateral adrenal removal to cut off the source of cortisol.

Following the operation, cortisol replacement must be given to maintain the hormonal balance in the body. This can usually be tapered off as the normal adrenal hormone production recommences. If the entire adrenal gland needs to be removed, cortisol replacement medication is required on a lifelong basis.

Complications of surgery may range from the general hazards associated with any surgery, such as infection, hemorrhage or anesthetic complications, to specific ones including:

  • Lifelong need for cortisol replacement
  • Loss of production of other hormones like thyroid hormone, growth hormone and the primary sex hormones, due to tissue loss following pituitary surgery
  • Nelson’s syndrome, the rare occurrence of a tumor in the pituitary that grows rapidly, producing skin darkening and visual symptoms

Radiation Therapy

Radiation therapy may be required, particularly for patients with a pituitary tumor that cannot be removed entirely with surgery.

There are two main modes of administration of radiotherapy, depending upon the situation and the patient’s health:

  • In small doses over a period of six weeks
  • A single, large dose (also called “stereotactic radiosurgery” or “Gamma Knife” surgery)

The choice of protocol between these depends largely on the specific case and the nature of the causative tumor. The first method has traditionally been used in such cases, but stereotactic radiosurgery is becoming the favored option for pituitary tumors. It offers a higher level of precision and creates less negative impact on the surrounding brain tissue. It may require to be combined with cortisol-inhibiting drugs as the effect may take from weeks to months to become fully apparent.


Medications can also help to control the production of cortisol in the body. They are most often used when other treatment methods, such as surgery and radiotherapy, are ineffective. Additionally, they may be beneficial prior to surgery in patients who have severe symptoms, because they can help to minimize surgery risk.

Medications that may be prescribed to regulate the production of cortisol in the adrenal gland include:

  • Ketoconazole
  • Mitotane
  • Metyrapone

Additionally, mifepristone is recommended for individuals with concurrent health conditions such as type 2 diabetes or glucose intolerance. Rather than decreasing the production of cortisol, the mechanism of action of mifepristone is to inhibit the effect of the hormone.

Pharmacotherapy may be associated with adverse effects such as fatigue, nausea, vomiting, hypertension, headache, myalgia and hypokalemia.


Further Reading

Last Updated: Jan 3, 2023

Yolanda Smith

Written by

Yolanda Smith

Yolanda graduated with a Bachelor of Pharmacy at the University of South Australia and has experience working in both Australia and Italy. She is passionate about how medicine, diet and lifestyle affect our health and enjoys helping people understand this. In her spare time she loves to explore the world and learn about new cultures and languages.


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