In Cushing’s disease, a tumor in the pituitary gland raises cortisol levels in the bloodstream, a condition known as hypercortisolism. The disease can be difficult to diagnose, because its symptoms develop gradually and are similar to those of Cushing’s syndrome, a broader category with other causes for Cushing’s onset, as well as with other illnesses.

The accurate identification of elevated levels of cortisol, a steroid hormone, followed by a determination of the cause of a person’s hypercortisolism is essential for diagnosing and treating Cushing’s disease.

Hypercortisolism and Cushing’s syndrome

Physicians generally begin assessing symptoms with a physical exam. They look for signs and symptoms associated with hypercortisolism and Cushing’s syndrome. Most often, these include a rounding of the face, the growth of fatty tissue between the shoulders, and thining skin with bruises and stretch marks. However, these are also symptoms of more common conditions, such as alcoholism, depression, an underactive thyroid gland, and high blood pressure.

If hypercortisolism is suspected, laboratory tests will be ordered to check a person’s cortisol levels. These may include a:

  • Urine test. People are asked to collect urine specimens at home over a 24-hour period to provide an extended view of cortisol levels.
  • Blood test. This test usually begins with a dexamethasone tablet to swallow prior to blood being drawn. In people with healthy cortisol levels, this drug should completely suppress cortisol production, so a blood sample will show an insignificant amount of cortisol. Levels that fail to drop noticably could be an indication of hypercortisolism.
  • Saliva test. Cortisol levels typically drop in the evenings, so a person may be asked to collect saliva samples at home between the late evening and early morning hours. Samples from a healthy person will be low in cortisol, characteristic of this hormone’s daily cycling, whereas levels in a person with Cushing’s syndrome will remain high.

Although none of these tests are conclusive on their own, an abnormal result in any assessment should be reason to investigate further for Cushing’s syndrome.

Determining hypercortisolism’s cause

After diagnosing Cushing’s syndrome, the physician will need to identify what is triggering a person’s high cortisol levels. Unlike other causes of hypercortisolism, Cushing’s disease can easily be identified by blood concentrations of an additional hormone, called the adrenocorticotropic hormone (ACTH). This hormone is released from the pituitary gland to stimulate the production of cortisol in the adrenal glands. Raised ACTH levels will clearly indicate an abnormality with the pituitary gland, a telltale sign of Cushing’s disease.

Should ACTH test results be unclear, physicians may request an MRI or CT scan to determine if a tumor exists on the pituitary gland.

People with hypercortisolism and no evidence of a pituitary tumor and negative ACTH test results will not have Cushing’s disease, but could have Cushing’s syndrome.

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