Cushing’s disease treatment options

Last updated July 13, 2023, by Patricia Silva, PhD
Fact-checked by Joana Carvalho, PhD

A number of specific therapeutic approaches are available for treating Cushing’s disease, including surgery, medications, and other procedures. The main goal of these treatments is to reduce the levels of the steroid hormone cortisol in the body and thus ease the physical, mental, and hormonal changes associated with the rare disease.

The first-line treatment usually recommended for Cushing’s disease is the surgical removal of the pituitary tumor that typically causes the disorder.

Cushing’s disease results from tumors in the brain’s pituitary gland, which is responsible for the production of several essential hormones. One of them is ACTH, or the adrenocorticotropic hormone, which stimulates the adrenal glands, located on top of the kidneys, to produce needed cortisol.

When too much ACTH is produced, however, as happens in Cushing’s disease, the levels of cortisol in the body rise to excess. This can lead to a variety of symptoms, including weight gain, fat accumulation in certain parts of the body, high blood pressure, and high blood sugar levels.

Cushing’s disease is a form of Cushing’s syndrome, an umbrella term for diseases characterized by an excess of cortisol in the body. Estimates indicate that up to 70% of all cases of endogenous Cushing’s syndrome — forms of the syndrome in which excess cortisol is driven by internal factors — are the result of Cushing’s disease.

Updated guidelines for the diagnosis and management of Cushing’s disease were published in 2021, based on academic and medical discussions promoted by the Pituitary Society.

Transsphenoidal adenomectomy

The most common procedure to remove pituitary tumors is transsphenoidal adenomectomy. It allows the removal of the tumor with minimal damage to the surrounding structures. The surgical team accesses the pituitary gland through the sphenoid sinus — a hollow space behind the nasal passages and below the pituitary gland.

If performed in specialized centers and by an experienced pituitary surgeon, this type of surgery is reported to result in an overall cure rate, or full remission, of Cushing’s disease for 80% to 90% of patients. A higher success rate is seen with smaller tumors.

However, reported remission rates vary considerably, mainly due to differences in the criteria used to define disease remission.

In some cases, a second transsphenoidal adenomectomy is required to fully remove tumor tissue; in others, the initial surgical procedure is paired with a second form of treatment, such as radiation therapy or certain medications.

Given the complexity of the procedure, the guidelines recommend patients undergo surgery in specialized Pituitary Tumor Centers of Excellence. Patients also are advised to have the surgery performed by an experienced pituitary neurosurgeon.

Follow-up for all patients should be conducted by a multidisciplinary team, including a pituitary endocrinologist.

Lifelong monitoring for disease recurrence is required.

Radiation therapy

Radiation therapy, or radiotherapy, involves the use of high-energy beams to eliminate cancer cells. It can be an option for Cushing’s disease patients who are not eligible for surgery, or as a second-line treatment when the initial surgical procedure fails to completely remove the pituitary tumor.

Progress in radiation therapy techniques in the last few decades has led to improvements in tumor targeting, effectively preventing the exposure of other brain structures near the pituitary gland to radiation.

Modern stereotactic radiation techniques rely on computer-assisted planning and specifically designed frames or fixation systems for patient positioning. These techniques offer a more precise head restraint so that radiation is applied exactly on the tumor from several different angles. This type of therapy delivers a high but precise radiation dose, minimizing the irradiation of surrounding healthy tissues.

The benefits of radiation therapy for Cushing’s disease are usually slower than those from surgery in controlling excess ACTH production. In fact, it can take months or even years until hormone overproduction is fully under control. Medicines that help control cortisol levels are recommended for Cushing’s disease patients while waiting for the effects of radiation therapy to be fully realized. Lifelong monitoring for pituitary hormone deficiencies and disease recurrence also is required.

Medications

Medications can help control cortisol levels; they usually are given in combination with surgery or radiation therapy. They also may be used as a first-line treatment when neither surgery nor radiation are good or viable options.

Cushing’s disease medications can have several different targets. They may be designed for the pituitary gland, the adrenal glands, or the cortisol receptors. A specific treatment is prescribed based on a patient’s particular clinical scenario.

• Medications targeting the pituitary gland and/or tumor typically aim to lower ACTH production, subsequently reducing cortisol levels. Such therapies include Signifor and Signifor LAR (pasireotide formulations).
• Drugs targeting the adrenal glands work to inhibit cortisol production. Examples include Recorlev (levoketoconazole) and Isturisa (osilodrostat).
• Cortisol receptor blockers are designed to mitigate the effects of cortisol in the body. One such medication is Korlym (mifepristone), which is indicated to lower high blood sugar (glucose) levels in patients with endogenous Cushing’s syndrome who have type 2 diabetes or glucose intolerance, and for whom surgery is not an option, or has been ineffective.

Ketoconazole (marketed as Ketoconazole HRA in the European Union) and Metopirone (metyrapone) are both approved in the EU to treat patients with endogenous Cushing’s syndrome, and are used off-label to treat Cushing’s in the U.S. Both work on the adrenal glands to suppress cortisol production. In the U.S., metyrapone is indicated for use in tests to assess the function of the pituitary gland.

Cabergoline also can be used off-label in the treatment of Cushing’s disease. The therapy works on the pituitary gland to decrease the production of ACTH, and has been shown to normalize cortisol levels in some patients and induce disease remission.

Lysodren (mitotane), a therapy approved to treat adrenal cancer, also has been used off-label to control high cortisol levels in some patients with Cushing’s disease. It is used because of its ability to suppress the production of cortisol.

For all patients receiving medication, regular monitoring for treatment efficacy is required.

In addition, several experimental medications are now being explored for the treatment of Cushing’s disease.

Adrenalectomy

One therapeutic strategy for Cushing’s disease, involving the removal of one or both of the adrenal glands, is a procedure referred to as an adrenalectomy. This surgery can be used to reduce cortisol levels in patients with persistent or recurrent Cushing’s disease for whom other forms of treatment have failed.

This technique can control excessive cortisol production almost immediately, with a success rate of 100%. However, the lack of the adrenal glands makes lifelong adrenal hormone replacement therapy necessary for most patients to maintain a proper hormonal balance and functioning. For this reason, this type of surgery often is considered a last resort treatment.

Given that the pituitary gland is in the origin of Cushing’s disease — and not the adrenal glands — routine monitoring and ACTH measurements are required in patients who undergo adrenalectomy.

Chemotherapy

Chemotherapy — the use of drugs to destroy cancer cells — might be required in cases where the tumor in the pituitary gland is cancerous (pituitary carcinoma) or has spread, or metastasized, to other body parts. This is a rare occurrence as most pituitary gland tumors are benign.

According to the American Cancer Society, the drug temozolomide is often the first chemotherapeutic agent used in cases of pituitary carcinomas, sometimes together with radiation therapy. The success of this strategy has been reported in a few case reports.

Lifestyle changes

A few lifestyle changes may help people with Cushing’s disease better manage the condition and avoid more serious health complications. Among the healthy habits recommended for patients are eating a balanced diet, practicing regular exercise, and using stress-managing techniques.

Cushing’s disease can cause high blood pressure. Therefore, a diet low in sodium (salt) is recommended. Patients should avoid fast food and processed foods as these are typically high in salt.

The disease also can cause blood sugar levels to rise; thus, patients should limit their sugar intake and follow a diet rich in whole grains, vegetables, fruits, and fish. This type of diet also helps lower cholesterol levels, which can be high in Cushing’s patients.

Additionally, increasing the intake of calcium and vitamin D are important, as Cushing’s has been linked to osteoporosis — a condition causing the bones to become weaker and more prone to fracture — and reduced bone density.

Another relevant lifestyle change is to reduce or even eliminate alcohol intake, as heavy drinking can interfere with the body’s hormonal system and increase cortisol levels, thereby further intensifying Cushing’s disease symptoms. As part of a healthy lifestyle, and to avoid potential health complications, tobacco use also should be avoided.

The high levels of cortisol characteristic of the disease have an impact on the body’s metabolism and often result in a rapid weight gain. Patients are therefore advised to reduce their calorie intake to prevent excessive weight gain.

Exercise is important to control weight and improve muscle strength. Low-impact exercises with a moderate intensity, such as swimming, cycling, and walking, are good options as they do not add increased stress on the skeletal and joint structures.

Furthermore, learning and applying stress management techniques can help decrease stress and anxiety, and consequently reduce cortisol levels and alleviate some Cushing’s disease symptoms. Stress management techniques include activities such as meditation, yoga, deep breathing, mindfulness, painting, and walking outdoors.

Any type of lifestyle change should be discussed with an individual’s healthcare team, so as to identify the most appropriate options based on each patient’s condition and preferences.

Cushing’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.