What is the dexamethasone suppression test used for?
There are two tests that use dexamethasone (a synthetic cortisol) for diagnosing Cushing’s disease or Cushing’s syndrome-- a "LOW DOSE" and a "HIGH DOSE" test. The low dose dexamethasone suppression test can be used to screen for the presence of hyperadrenocorticism (Cushing’s disease) and in many cases it will differentiate the type of Cushing’s disease that is present. The high dose dexamethasone test is used when the patient has been confirmed with Cushing’s disease by means of the low dose test, but is one of the cases in which the low dose test has not clearly differentiated the type of Cushing’s disease that is present. Both the low dose and the high dose dexamethasone suppression tests take 8 hours to complete and involve three blood samples. The first sample is taken prior to the injection of dexamethasone, and the second and third samples are taken at 4 and 8 hours following the dexamethasone injection. The difference between the two tests is in 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?
Cortisol (also called cortisone) is produced and stored in the adrenal gland. Normally, it is released in times of stress, and enables the body to respond rapidly and appropriately to the stress. With Cushing’s syndrome, there is an excessive amount of cortisol that is circulating all the time. In a healthy dog, ACTH (adrenocorticotropic hormone) 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 lowering of the blood cortisol level – a controlling mechanism called a negative feedback loop. This feedback loop is capable of causing rapid changes in blood cortisol levels in response to the body’s needs. However, in a dog with Cushing’s syndrome, this controlling mechanism is not working correctly. The dexamethasone suppression tests exploit the negative feedback mechanism in order 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 timed intervals following dexamethasone injection, and the amount of cortisol in each of the samples is compared.
What sort of result will a dog with Cushing’s disease have?
With Cushing’s disease the negative feedback loop is diminished or lost due to either excess secretion of ACTH by the pituitary gland, because of a tumour, or due to excess production of cortisol by the adrenal glands, also often related to a tumour.
With the pituitary type of Cushing’s disease, a SMALL AMOUNT of suppression in cortisol production may be seen in the 4 or 8-hour blood samples. This is because some of the natural negative feedback mechanism usually remains. .
With Cushing’s disease that is caused by adrenal disease, NO reduction in blood cortisol concentrations will be noted in the 4 or 8-hour samples. This is because the negative feedback loop is lost completely.
Will the low dose dexamethasone test always allow diagnosis of Cushing’s disease?
No.
In most instances, the low dose dexamethasone suppression test will allow both the diagnosis of Cushing’s disease to be made and also give us an indication of the type of Cushing’s disease (pituitary gland versus adrenal gland origin).
When is it necessary to perform the HIGH DOSE dexamethasone test?
Occasionally with the pituitary form of Cushing’s disease, there is no suppression of the cortisol blood levels (because the negative feedback loop is more resistant to the effects of the synthetic cortisol). A higher dosage of dexamethasone (high dose dexamethasone suppression test) may therefore be required to overcome this resistance and demonstrate the negative feedback mechanism.
Cushing’s disease caused by an adrenal gland tumour 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 is supportive of an adrenal origin to the Cushing’s disease.
In summary, if we get a reduction in cortisol levels at 4 and/or 8 hours after either dose of dexamethasone, then we have diagnosed pituitary origin Cushing’s. If the levels don’t budge from the high values of the 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 hyperadrenocorticism (Cushing’s disease), dogs with chronic medical conditions and those in other stressful situations, may also fail to suppress.
It is important therefore that other medical conditions be ruled out by blood screening tests and that there are strong supportive clinical signs consistent with Cushing’s disease before we undertake dexamethasone suppression testing.
Why does it matter which type of Cushing’s disease the dog has?
If your dog has pituitary dependent Cushing’s disease the treatment is different than it would be if your dog 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.
Based on material written by Kristiina Ruotsalo, DVM, DVSc, Dip ACVP &
Margo S. Tant BSc, DVM, DVSc. and modified with permission from Lifelearn Inc.
© Copyright 2004 Lifelearn Inc.
