The low-dose dexamethasone suppression test (LDDS test), considered by many endocrinologists to be decidedly better than the adrenocorticotropic (ACTH) stimulation test, is both diagnostic and discriminating, making it possible to differentiate forms of pituitary-dependent hyperadrenocorticism (PDH) from forms of adrenal-dependent hyperadrenocorticism (ADH) by taking advantage of the negative feedback mechanism of cortisol on the release of ACTH. Indeed, in a healthy dog, the administration of exogenous corticosteroids blocks the release of ACTH by the pituitary gland and thus cortisol is not produced by the adrenal glands. The reduction in blood cortisol levels is detected as early as 2-3 hours after the intravenous administration of dexamethasone and can last for 8-48 hours.
Performing the test
The test protocol involves measuring the blood cortisol levels at baseline and 4 and 8 hours after the intravenous administration of 0.01 mg/kg of dexamethasone.
Interpretation of results
The blood cortisol level at 8 hours enables a suspected diagnosis of hypercortisolism to be confirmed: the test is considered negative if the blood cortisol level at 8 hours is below 1 μg/dl. Values between 1 μg/dl and 1.4 μg/dl indicate an equivocal response to the test; values higher than 1.4 μg/dl confirm the diagnosis of hypercortisolism.
In the majority of cases, blood cortisol levels measured 4 hours after the administration of dexamethasone make it possible to differentiate subjects with PDH from those with ADH.
In a healthy subject, blood cortisol levels decrease to below 1.4 μg/dl as early as 4 hours after the administration of dexamethasone and remain low even after 8 hours.
Subjects with PDH may exhibit different types of responses at 4 hours after the administration of dexamethasone:
- 20% of subjects show no suppression of blood cortisol, thus resembling subjects with ADH.
- an additional 20% of subjects have slight suppression.
- 30-40% of subjects have a cortisol level at 4 hours that is more than 50% lower than the basal value, but not below 1.4 μg/dl.
- in the remaining 25% of subjects, the blood cortisol level at 4 hours is below 1.4 μg/dl.
In the first two cases it is impossible to distinguish PDH from ADH; the test simply gives the diagnostic confirmation of hypercortisolism. It follows that a clear response to the suppression test is obtained in only 60% of subjects with PDH.
On the other hand, in subjects with ADH, the adrenal glands do not suppress cortisol production. However, the test may be equivocal when there is an apparent suppression of blood cortisol at 4 hours after the administration of dexamethasone, which is probably actually a slight, random and temporary fluctuation in the blood cortisol level occurring at the time the blood sample is taken.
It is important to note that a false positive result can be caused by the animal’s stress level. In this regard, in order to limit possible false positive test results, it is a good idea not to perform other diagnostic procedures, such as ultrasound scans and anaesthesia, on the day the LDDS test is performed. Furthermore, the LDDS test should preferably not be performed on the same day as the ACTH stimulation test.