Medical Management of Cushing's Disease
Written by: Aaron Cohen-Gadol, MD
Last Updated: October 17, 2024
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Cushing's disease is a rare medical condition characterized by the excessive production of cortisol. Cortisol, commonly known as the "stress hormone, plays a crucial role in regulating various processes in the body, including metabolism, immune function, and our stress response. It is specifically caused by a brain tumor in the pituitary gland.
The pituitary gland, a small pea-sized structure located at the base of the brain, produces adrenocorticotropic hormone (ACTH). This stimulates the adrenal glands above the kidneys to produce cortisol. In Cushing's disease, a tumor develops in the pituitary gland and releases more ACTH than the body needs. This eventually leads to an excessive amount of cortisol in the body.
One of the hallmark symptoms of excess cortisol is weight gain, especially in the upper body and face, resulting in a rounded and swollen appearance, The skin may become thin and fragile, with a tendency to bruise easily.
Muscle weakness and wasting are common, leading to fatigue and reduced physical strength. In addition, high blood pressure and elevated blood sugar levels are also associated complications.
Although surgery is the primary treatment option, medications may also play a role. In this article, we will discuss medications for Cushing's disease and answer commonly asked questions.
What Is the Primary Treatment for Cushing’s Disease?
Pituitary surgery is the only potentially curative treatment option for Cushing's disease. This type of surgery can improve or cure symptoms in 80% - 85% of patients. The transnasal transsphenoidal approach is often utilized to access the pituitary tumor by inserting long surgical instruments into the nasal cavity.
Figure 1. Removal of bone through the nasal passages (left) to reach a tumor at the base of the brain (right).
Medications for Cushing’s Disease
Medications are not the primary treatment option for Cushing's disease, however, treatment in the form of medications for high cortisol levels are available. they may be administered if cortisol levels remain elevated after surgery, or if surgery cannot be performed.
These medications work by reducing cortisol production or blocking the effects of cortisol in the body. The choice of medication will be based on various factors, including the severity of symptoms, other present medical conditions, and the patient's overall health.
Pasireotide (Signifor): Pasireotide (Signifor) is a somatostatin hormone analogue. It acts similarly to somatostatin and can effectively bind to ACTH-secreting tumors, leading to the inhibition of ACTH secretion.
It is important to note that pasireotide may lead to increased blood sugar levels (hyperglycemia). Therefore, patients with diabetes mellitus should be carefully evaluated, and their current diabetic therapies should be optimized before starting pasireotide treatment.
Ketoconazole: Ketoconazole is an antifungal medication that has been used off-label to treat Cushing's disease. It is considered a cortisol synthesis inhibitor, meaning it can suppress the production of cortisol and is used as treatment for high cortisol.
It's important to note that ketoconazole should only be used under the supervision of an experienced endocrinologist, as it may have significant side effects and interactions with other medications. Common side effects of ketoconazole may include nausea, vomiting, abdominal pain, headache, and changes in liver function tests.
Osilodrostat (Isturisa): Osilodrostat (Isturisa) is a medication that belongs to a class of drugs called cortisol synthesis inhibitors. Osilodrostat works by blocking an enzyme called 11-beta-hydroxylase, which is involved in the production of cortisol.
Some common side effects of osilodrostat include nausea, diarrhea, headache, fatigue, and decreased appetite. Osilodrostat was approved by the U.S. Food and Drug Administration (FDA) in 2020 and has shown promising results in clinical trials for the management of Cushing's disease.
Metyrapone (Metopirone): Metyrapone (Metopirone) is classified as a cortisol synthesis inhibitor, meaning it works by blocking an enzyme called 11-beta-hydroxylase, which is involved in the production of cortisol.
Some common side effects of metyrapone include gastrointestinal disturbances such as nausea, vomiting, and abdominal pain. It can also lead to dizziness and fatigue.
Mifepristone (Korlym, Mifeprex): Mifepristone is a glucocorticoid receptor antagonist, which means it blocks the effects of cortisol in the body. By doing so, it helps to alleviate the symptoms associated with excessive cortisol levels in individuals with Cushing's syndrome or disease.
As with any medication, mifepristone may have side effects, including nausea, fatigue, and headaches.
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Can Radiation Therapy Be Used?
In cases where surgical intervention is not successful, a combination of medication and radiation therapy can help to manage the condition effectively. Radiation therapy can help to prevent the residual tumor from growing, while medications can help to improve symptoms.
Radiation therapy can be administered via fractionated radiotherapy or stereotactic radiosurgery. In fractionated radiotherapy, the total radiation dose is divided into multiple smaller doses. The procedure is performed five times per week over several weeks.
On the other hand, stereotactic radiosurgery delivers a single high doses of radiation. Despite having "surgery" in its name, no incision is involved. It simply refers to the highly precise nature of its targeting beams.
Both fractionated radiotherapy and stereotactic radiosurgery are outpatient procedures, and the exact schedule and dose intensity will be determined based on your individual case.
Key Takeaways
- Cushing's disease is a rare condition caused by a pituitary adenoma (tumor) that leads to excessive production of cortisol, a hormone produced by the adrenal glands.
- Transsphenoidal surgery is the primary treatment for Cushing's disease, aiming to remove the pituitary adenoma causing excessive cortisol production.
- Medications like ketoconazole, osilodrostat, mifepristone, pasireotide, and metyrapone can be used to lower cortisol levels when surgery is not feasible or fully effective.
- Radiation may be used after surgery to prevent tumor regrowth or as an alternative treatment option for cases where surgery or medical therapy is not successful.
