What Is Cushing’s Disease?

Cushing’s disease is a form of Cushing’s syndrome, which encompasses all disorders in which there is an excess of the hormone cortisol in the body, a condition known as hypercortisolism. It is estimated that Cushing’s disease accounts for approximately 70% of all cases of Cushing’s syndrome.

The disorder tends to be diagnosed more often in adults, ages 30–40, and typically affects women more than men. However, the exact reason for that remains unclear.

Causes of Cushing’s disease

The presence of benign — non-cancerous — tumors in the brain’s pituitary gland normally cause Cushing’s disease. Such tumors trigger the excessive production of adrenocorticotropic hormone, known as ACTH. The adrenal glands, which sit atop the kidneys, perceive ACTH as a signal to produce and release cortisol. Over time, this leads to the overproduction of cortisol and to the onset of Cushing’s.

Some genetic mutations also have been found to cause Cushing’s disease in a few rare cases.

Symptoms of Cushing’s disease

Because cortisol affects multiple bodily processes, its excessive levels also cause a variety of physical, mental, and hormonal changes.

Common symptoms of Cushing’s disease include unusual weight gain and fat accumulation around the torso, face, above the collarbone, or between the shoulders. Skin changes, including easy bruising and the appearance of stretch marks on different parts of the body, also are common.

As with other hormones, cortisol affects people differently based on their age and gender. Women with Cushing’s disease may experience irregular menstrual cycles and excessive hair growth, while men may experience erectile dysfunction, or an inability to get or keep an erection. In children and adolescents, hypercortisolism associated with Cushing’s may delay growth and physical development.

Diagnosis of Cushing’s disease

Because symptoms of Cushing’s disease sometimes overlap with those of other conditions, and typically do not manifest all at the same time, its diagnosis can be challenging.

Diagnosis of Cushing’s disease typically involves a series of tests, aimed first at confirming the presence of hypercortisolism and then at determining its cause.

Cortisol levels can be measured in the blood, urine, and saliva to assess the presence of hypercortisolism. Once hypercortisolism has been identified, physicians may look for elevated levels of ACTH, as these will suggest the presence of a pituitary tumor. Additional imaging tests, including MRI scans, and sometimes invasive tests — for example, petrosal sinus sampling, also may be needed to confirm the diagnosis.

Treating Cushing’s disease

Cushing’s disease can be treated surgically, radiologically, and pharmacologically — so by surgery, radiation, or through medications.

Surgically removing pituitary tumors is usually the first choice of treatment. This is typically done through a procedure called transsphenoidal adenomectomy, in which surgeons access the pituitary gland either through the nostrils or the upper lip. Patients may need cortisol replacement therapy after having surgery, until they can once again maintain cortisol levels within a healthy range naturally.

Removing the adrenal glands is a second surgical option that is usually reserved for patients for whom pituitary surgery was unsuccessful. Although this procedure is almost always effective, patients must receive hormone replacement therapy for the rest of their lives following surgery. In addition to cortisol, patients must receive aldosterone, another hormone produced by the adrenal glands that controls the body’s salt and water balance.

Radiation therapy also can be used to shrink or destroy pituitary tumors. Since such therapy carries a greater risk of damaging healthy areas of the pituitary gland, this type of treatment is usually reserved for patients who are ineligible for pituitary surgery, or for those in whom the procedure failed to completely remove the tumor.

Finally, various medications, such as Metopirone (metyrapone) and Isturisa (osilodrostat), can help control cortisol levels. For greater effect, patients often are prescribed combinations of medicines that target different aspects of cortisol production.


Last updated: May 28, 2021


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