Radiation Therapy For Cushing's Disease

Cushing's disease is a hormone disorder caused by a brain tumor arising from the pituitary gland. Although this brain tumor is often benign (non-cancerous), the production of excess hormone can cause a variety of symptoms.

Elevated levels of cortisol, commonly known as the "stress hormone", is characteristic of this condition. Over time, this can lead to skin changes, fatigue, weakness, weight gain, and easy bruising, among other symptoms.

While surgery is typically the primary mode of treatment, radiation therapy is a valuable adjunct. In this article, we discuss the role of radiation therapy in the treatment of Cushing's disease

Cushing's disease treatment options include surgery, radiation, medications, or a combination of the above. Surgical intervention is often the primary treatment approach and serves as the only potentially curative option available.

Most surgeons will access the tumor through the nose in a special procedure called transsphenoidal surgery. In this minimally invasive approach, surgical instruments are passed through the nasal cavity to reach the pituitary tumor.

Compared to a traditional open approach (craniotomy), no incision in the scalp is necessary. Additionally, the recovery time for transsphenoidal surgery is typically shorter than for a craniotomy. However, a craniotomy may be performed in certain large, more complex cases. 

While surgical removal of the tumor is the most direct way to address the disease, not all patients may be suitable candidates for surgery. For those who are not optimal candidates for surgery or who require additional treatment after surgery, medications and radiation therapy come into play.

Radiation therapy involves the use of high-energy beams to precisely target and damage cells in a desired area. Radiation therapy can vary based on the beam type (e.g., photons, protons), the location of the radiation source (e.g., internal or external), the intensity of the dose (e.g., radiosurgery or fractionated radiotherapy), and even the technology used to control the beams. 

Radiation therapy serves as a treatment option for Cushing's disease, primarily when surgical intervention is not viable or as an adjuvant treatment after surgery to suppress growth from remnant tumor.

The goal is to normalize hormone levels, alleviate symptoms, and impede tumor growth. Radiation can be delivered via fractionated radiotherapy or stereotactic radiosurgery.

In this approach, the total radiation dose is divided into smaller doses, known as fractions, that are usually administered once a day, five days a week (Monday through Friday), over a span of several weeks.

The treatment period is typically 5 to 6 weeks, though the exact schedule can vary depending on the treatment protocol, the radiation oncology center, and the specific needs of the patient. Additionally, it can take time for the effects of fractionated radiotherapy to be apparent. 

Reduction in cortisol levels and symptom relief may occur several months after the completion of radiotherapy and may take up to 2 years or more for the full effects to be observed.

During this latency period, patients are closely monitored, and medications may be used to control cortisol levels until the radiation therapy takes maximum effect.

In contrast to fractionated radiotherapy, stereotactic radiosurgery involves the administration of a single large dose of radiation in one extended session. The term "stereotactic radiosurgery" can sound intimidating, so let's start by understanding what each word in the term means.

"Stereotactic" pertains to advanced image-guidance methods that help to align radiation beams to the targeted area within the body. It acts similar to a GPS in that it helps the team to reach a specified location.

"Radiosurgery" is named so due to the remarkable precision of the radiation beams. It does not actually involve a surgical incision. Stereotactic radiosurgery can be administered via three distinct systems:

Gamma Knife Radiosurgery: Gamma Knife radiosurgery employs a highly precise and focused array of gamma radiation beams to treat small pituitary tumors responsible for Cushing's disease.

Without the need for surgical incisions, this procedure delivers radiation from multiple angles, converging precisely at the tumor site. The targeted radiation damages the tumor cells, impeding their growth and cortisol production.

Healthy surrounding tissues receive minimal radiation, reducing the risk of complications. This technique is particularly effective for small and deep-seated tumors that might be challenging to reach with traditional surgery.

Linear Accelerator (LINAC) Radiosurgery: Linear accelerator radiosurgery employs a machine called a linear accelerator to produce high-energy X-rays. These X-rays are precisely targeted at the tumor, effectively inhibiting tumor growth.

LINAC radiosurgery is versatile, capable of treating both small and larger tumors. These systems can move around the patient, enabling diverse angles of approach while minimizing radiation exposure to the neighboring tissues.

Heavy Charged Particles: This approach directs particles, specifically protons, with pinpoint precision toward a designated target. In contrast to photons, protons exhibit a unique dose distribution which maximizes radiation delivery to the tumor while sparing surrounding normal tissues.

However, there are a limited number of proton beam therapy centers around the world and research is still being conducted to determine the clinical advantages of proton versus photon beam therapies. 

The most common complication following radiation therapy for Cushing's disease is called hypopituitarism. This occurs when the normal pituitary gland is damaged and fails to produce enough hormones. Lifelong hormone supplementation may be necessary to provide appropriate levels of hormone for the body.

Other potential complications of radiation therapy to a pituitary tumor include the following:

• Cranial Nerve Injury: Radiation-induced damage to cranial nerves can occur, particularly when the tumor is near the optic chiasm or other cranial nerves. This can result in vision problems, or less commonly, facial numbness or weakness.  
• Radiation Necrosis: A rare but serious complication is radiation necrosis, where healthy adjacent tissues are harmed. This can lead to a range of symptoms such as headaches, memory impairment, alterations in personality, and seizures.
• Cognitive Dysfunction: Some patients may experience cognitive changes following radiation therapy, particularly if large volumes of brain tissue are irradiated.
• Radiation-Induced Edema: Brain swelling (edema) can occur, which may manifest as headaches, nausea, or worsening neurological symptoms. This is typically managed with corticosteroid medications. 
• Other Hormone Dysfunction: Besides hypopituitarism, patients may experience other hormone-related issues such as diabetes insipidus, which causes excessive thirst and urination.
• Skin Reactions: Acute reactions such as skin redness, hair loss, and scalp tenderness, can occur at the radiation site but are usually temporary.

It is important to note that the risk of these complications may vary depending on the type of radiation therapy used (e.g., conventional fractionated radiotherapy, stereotactic radiosurgery), the total dose delivered, the fractionation scheme, and the proximity of the target volume to critical structures. Long-term follow-up with a multidisciplinary team is essential to monitor for these complications and to initiate appropriate interventions when necessary.

• Transsphenoidal surgery is the primary treatment for Cushing's disease.
• Radiation therapy is a valuable option for managing Cushing's disease when surgery may not be feasible or effective.
• It involves the targeted application of high-energy radiation to tumor cells, impeding their growth and cortisol production.
• Maximal treatment effects of radiation therapy may take months to years

• Endocrine Society
• Pituitary Foundation
• Urology Care Foundation
• National Adrenal Diseases Foundation