Dexamethasone Suppression Tests

By Malcolm Weir, DVM, MSc, MPH; Krista Williams, BSc, DVM, CCRP; Kristiina Ruotsalo, DVM, DVSc, Dip ACVP & Margo S. Tant BSc, DVM, DVSc

What is the purpose of a dexamethasone suppression test?

Dexamethasone is a synthetic cortisol. Two tests use dexamethasone for diagnosing hyperadrenocorticism (Cushing's disease or Cushing's syndrome). They are the "low dose" and the "high dose" dexamethasone suppression tests.

The purpose of the low dose dexamethasone suppression test is to screen for the presence of Cushing's disease and, in many cases, it determines the type of Cushing's disease that is present.

When the low dose dexamethasone suppression test confirms Cushing's disease but does not clearly differentiate the type of Cushing's disease, then the high dose dexamethasone suppression test may be used.

Both the low dose and the high dose dexamethasone suppression tests take eight hours to complete and involve three blood samples.

  • The first sample is taken before the injection of dexamethasone.
  • The second sample is taken four hours after the dexamethasone injection. 
  • The third sample is taken eight hours after the dexamethasone injection.

The only difference between the low dose and high dose tests is the amount of dexamethasone that is injected. The two tests must be run on different days.

What is the basis of the dexamethasone suppression tests?

The two adrenal glands produce and store cortisol. Normally, cortisol is released from the adrenal glands in times of stress, and it prepares the body to respond rapidly and appropriately to the stress. With Cushing's disease, an excessive amount of cortisol circulates all the time.

In a healthy dog, adrenocorticotropic hormone (ACTH) is secreted by the pituitary gland and stimulates the adrenal glands to produce or secrete cortisol. As the blood cortisol level increases, it causes the pituitary gland to lower its production of ACTH, which results in a decreasing blood cortisol level – a controlling mechanism called a negative feedback loop. This feedback loop can cause rapid changes in blood cortisol levels in response to the body's needs. However, in a pet with Cushing's syndrome, this controlling mechanism does not work correctly.

Dexamethasone suppression tests use the negative feedback mechanism to diagnose the presence of Cushing's disease. When healthy dogs are given an injection of synthetic cortisol (dexamethasone), the level of ACTH is suppressed, causing a decrease in cortisol levels in the blood for a period of time. Blood samples are taken at four and eight hours following dexamethasone injection, and the amount of cortisol in each of the samples is measured and compared.

What sort of result will a dog with Cushing's disease have?

With Cushing's disease, the negative feedback loop is reduced or lost, due to excess secretion of ACTH by the pituitary gland because of a tumor, or due to excess production of cortisol by the adrenal glands, also often caused by a tumor.

With the pituitary type of Cushing's disease, a small amount of cortisol suppression may occur in the four hour or eight hour samples because some of the natural negative feedback mechanism remains.

With Cushing's disease caused by adrenal disease, no reduction in blood cortisol concentrations will be noted in the four hour or eight hour samples because the negative feedback loop is completely lost.

Will the low dose dexamethasone test always allow diagnosis of Cushing's disease?

In most instances, the low dose dexamethasone suppression test allows the diagnosis of Cushing's disease, but not always. This test also gives an indication of the type of Cushing's disease (pituitary gland versus adrenal gland origin).

When may the high dose dexamethasone test be performed?

Occasionally, with the pituitary form of Cushing's disease, the low dose dexamethasone test shows no suppression of blood cortisol levels, because the negative feedback loop is more resistant to the effects of the synthetic cortisol. In these cases, a higher dosage of dexamethasone may be required to overcome this resistance and demonstrate the negative feedback mechanism (high dose dexamethasone suppression test).

Cushing's disease caused by an adrenal gland tumor is resistant to the effects of both low and high doses of dexamethasone. Therefore, failure of blood cortisol levels to decrease after using both the low and high doses of dexamethasone suggests an adrenal origin to the Cushing's disease.

In summary, if your veterinarian observes a reduction in cortisol levels four and/or eight hours after either dose of dexamethasone, then a diagnosis of pituitary origin Cushing's disease is made. If the levels do not budge from the high pre-injection sample, then the diagnosis is adrenal origin.

Are there any other reasons why cortisol levels may fail to suppress?

Yes. While a lack of suppression to dexamethasone injection is supportive of Cushing's disease, animals with chronic medical conditions and those in other stressful situations may also fail to suppress.

Therefore, it is important that other medical conditions be ruled out by screening tests that may include additional blood tests, urine tests, and abdominal ultrasound. It is also important that the patient shows strong, supportive clinical signs consistent with Cushing's disease before dexamethasone suppression testing is undertaken.

Why does it matter which type of Cushing's disease the pet has?

If the pet has pituitary-dependent Cushing's disease, the treatment is different than it would be if the pet has adrenal-origin Cushing's disease. Cushing's disease caused by an enlarged adrenal gland may be treated surgically or medically. Adrenal tumors may be malignant or benign. Pituitary tumors that cause Cushing's disease are usually benign, and their treatment is medical. See handout “Cushing’s Disease in Dogs” for more information.

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