Cushing Syndrome · What Is It, Causes, Treatment, and More

Cushing syndrome, also called hypercortisolism, is a set of symptoms resulting from exposure to high levels of the hormone cortisol. Cortisol is typically produced in response to stress; it helps regulate blood pressure and blood sugar, reduce inflammation, and metabolize food.   

Cortisol production and release is stimulated by a series of interactions with other hormones. First, the hypothalamus secretes corticotropin-releasing hormone (CRH) which then stimulates the anterior pituitary gland to produce adrenocorticotropic hormone (ACTH). Ultimately, ACTH signals cortisol production from the adrenal glands, which are small glands located on top of each kidney. 

There are many potential causes of Cushing syndrome. The most common is long-term use of glucocorticoids, such as prednisone or dexamethasone, which are typically used to treat inflammatory disorders, like asthma, rheumatoid arthritis,or lupus. Glucocorticoids act as a synthetic form of cortisol, therefore long-term use can lead to Cushing syndrome.  

Less frequently, Cushing syndrome may develop due to a tumor that affects the hormones involved in stimulating cortisol production. Pituitary tumors that produce ACTH in excess, as seen in Cushing disease, are the most common tumor type. Sometimes, ectopic ACTH-producing tumors (i.e., tumors that secrete ACTH outside of the pituitary gland) may occur, such as in the lungs or pancreas, and are often cancerous.

Rarely, Cushing syndrome can be caused by an adrenal tumor, which is typically benign, or non-cancerous. 

Diagnosis of Cushing syndrome begins with a thorough medical history and a physical exam. If Cushing syndrome is suspected, laboratory tests, such as 24-hour urinary free-cortisol test, overnight low-dose dexamethasone suppression test, or late-night salivary cortisol test, are typically performed. Oftentimes, the diagnosis of Cushing syndrome is only confirmed after two or more tests demonstrate elevated levels of ACTH and cortisol. 

Further testing, including imaging tests like a CT or MRI, may be used to assess whether a tumor is the underlying cause. However, some pituitary tumors are so small they may not appear on imaging and, instead, require petrosal sinus blood samples, which involves taking blood samples from the small sinus veins that drain from the pituitary. 

The treatment of Cushing syndrome varies depending on the underlying cause. If caused by the use of glucocorticoids, treatment typically involves lowering the glucocorticoid dose or changing the medication to another steroid class or anti-inflammatory. If the medication is lowered or changed, it will be slowly tapered to avoid adrenal crisis caused by a sudden reduction of cortisol.  

When Cushing syndrome results from a tumor, the tumor is often surgically removed. If surgery is not a viable option (e.g., the tumor has metastasized) or does not relieve symptoms, radiation therapy may be utilized. After a pituitary tumor is removed, about 6-18 months of cortisol supplementation will typically follow the surgery. If both adrenal glands are removed, cortisol and other hormone supplementation will be needed for the duration of the individual’s life. 

Most of the time, Cushing syndrome can be cured since it typically results from long-term glucocorticoid use. However, despite appropriate treatment, many individuals experience residual symptoms from Cushing syndrome, including muscle weakness or cognitive impairment.  

Individuals with successful surgeries of benign pituitary, adrenal, or ectopic tumors have a 5-year survival rate of 95% and a 10-year survival rate of 90%. Unlike the benign tumors, 5-year survival rates for malignant tumors range from 50-81%.