Cushing S Disease in the Canine and Its Confirmation by Endocrine Diagnostic Testing

Cushing ’s Disease in the Canine and its Confirmation by Endocrine Diagnostic Testing

Cushing’s disease is the second most common endocrinopathy in the canine. Hypothyroidism takes first place as the most common endocrine disease in the canine. Cushing’s disease has been well characterized clinically and is normally thought of as a clinical diagnosis. With that in mind, confirmation by using a diagnostic tool provides for support of the clinical diagnosis. The most common clinical sign noted on clinical histories through the Texas Veterinary Medical Diagnostic Laboratory (TVMDL) is polyuria and polydipsia. Other common clinical signs include polyphagia and the “pot” bellied appearance along with some muscle wasting of the hind quarters in advanced cases. Often times, Cushing’s Disease will also suppress thyroid function giving the clinical appearance of hypothyroidism. Other biochemical tests are elevated such as serum alkaline phosphatase (ALT).

There are two common diagnostic tools for evaluating Cushing’s disease; the Low Dose Dexamethasone Test (LDD) and the adrenocorticotropic hormone (ACTH) Stimulation Test. Both confirmation tests have respective pros and cons. The LDD is designed to test the negative feedback system (in the normal adrenal dog, exogenous corticosteroid treatment will suppress the hypothalamo-pitutiary adrenal axis and give low or undetectable concentrations of cortisol). With the LDD test we are adding exogenous corticosteroids to induce negative feedback. If the feedback system is intact, then the cortisol will be suppressed at specific intervals. If the system is circumvented by over production of cortisol by the adrenal gland, suppression will not take place by giving exogenous corticosteroids in the majority of cases. One of the most popular diagnostic regimens for the LDD is to draw a baseline sample, administer 0.01 ug/kg of dexamethasone and obtain a 4 and 8 hour post dexamethasone injection sample. In the normal adrenal dog, exogenous corticosteroid treatment will suppress the hypothalamo-pitutiary adrenal axis and give low (< 1.0 ug/dl) or undetectable concentrations of cortisol post dexamethasone at 4 and 8 hrs. If the animal is hyper-adrenal (Cushing’ Disease), the 4 and 8 hour post dexamethasone sample will be elevated (> 1.0 ug/dl)

Using the ACTH stimulation test evaluates the reserve of the adrenal gland. In the hyper-adrenal patient the adrenal gland is usually hypertrophied and thus can produce/release more cortisol than the normal adrenal gland upon stimulation. In the normal adrenal canine, the post ACTH stimulation test results in concentrations less than 14.0 ug/dl. Concentrations that are greater than 20 ug/dl are considered confirmatory at TVMDL. The most common regimen for performing the ACTH stimulation test is to draw a baseline sample, give exogenous ACTH, IV or IM depending on the type of ACTH and drawing a post sample, either 1 hour or 2 hours post injection. The feedback system is not interrupted with this regimen. This test is designed to test the reserve of the adrenal gland by giving a pharmacological dose of ACTH and overriding any negative feedback of cortisol in circulation.

The most common question asked, is which test is better? Both tests are equal in their ability to confirm Cushing’s. The current dogma on the ACTH stimulation test is to reserve that for evaluating therapy for a Cushing’s patient. The cost of the ACTH can be expensive, but the time to post injection sample is much less than the LDD testing, from 1 to 2 hours post injection instead of 4 and 8 hours. The LDD test takes 8 hours to obtain samples post injection and therefore may be a limiting factor because of how long the test takes in order to get samples.

Other tests that are available include endogenous ACTH or Urine Cortisol Creatinine Ratio (UCCR) for evaluation of adrenal status. The endogenous ACTH test is usually reserved for differentiating between pituitary dependent hyper-adrenocorticism and adrenal dependent hyper-adrenocorticism. UCCR is reserved for screening for Cushing’s, and not necessarily for confirmation of Cushing’s. One point to remember, Cushing’s disease is a clinical diagnosis in the majority of cases.