Q & A: Prednisone and Cushing's Syndrome: Which Screening Test Is Best?

I'm treating a 10-year old, F/S Bichon Frise who has been on 2.5 mg of prednisone daily for months. Her appetite has always been good, but recently she has become extremely ravenous on the same dose of prednisone. In addition, lately she has become noticeably more polyuric and polydipsic (PU/PD). 

So, I suspect that naturally-occurring Cushing's syndrome may be developing — oddly, while taking predisone. We found not abnormalities on her routine lab work except an very high serum alkaline phosphatase activity of 1100 U/L (reference range < 100 U/L).

My thought is that stopping the predisone for a few days should be enough to allow for us to perform an ACTH stimulation test or a low-dose dexamethasone suppression test (LDDST). That amount of time will allow the predisone to leave the system so there won't be any interference with the testing. It would seem to me that an interval longer than a few days shouldn't be needed.

That being said, everyone keeps telling me it will take a few months for the adrenals to regenerate once I stop the prednisone. Presuming this dog has truly developed PDH or an FAT, does it make any sense to you that I should have to wait any longer than just a few day to let the prednisone out of the body?

My Response:

Good question. If this dog's pituitary and adrenal glands are "normal" (ie, she does not have naturally occurring Cushing's disease - either pituitary-dependent hyperadrenocorticism or a functional adrenal tumor), then the prednisone could feedback on the dog's normal pituitary gland to inhibit ACTH secretion. With time, the resulting low circulating ACTH concentrations would lead to atrophy of the inner 2 zones of the adrenal gland that secrete cortisol.

If you stop the prednisone for 24-48 hours and do an ACTH stimulation test in that dog, the results would likely show a low to low-normal basal cortisol with a "blunted" cortisol response to ACTH stimulation (generally > 2.0 ug/dl but < 6 ug//dl). Despite the suppression basal and ACTH-stimulated cortisol values, that same dog with iatrogenic hypoadrenocorticism could show clinical signs of iatrogenic hyperadrenocorticism (due to the direct glucocorticoid effects of the prednisone).

Now, if this dog really does have natural Cushing's syndrome (either pituitary-dependent hyperadrenocorticism or adrenal tumor), the doses of prednisone you are giving will NOT be high enough to shut off pituitary ACTH secretion or suppress adrenal cortisol section. (This "resistance" to glucocorticoid negative feedback in Cushing's disease is the whole physiologic basis for use of the low-dose dexamethasone suppression test.).

So in this dog with Cushing's syndrome, performing an ACTH stimulation test after being off the prednisone for 24-48 hours would show a normal to high basal cortisol with a high-normal to exaggerated serum cortisol response. In other words, the prednisone would not affect the ACTH stimulation test because the adrenal cortex would still be hypertrophied.

Another important point: in this scenario, you want to use and ACTH stimulation test, not the low-dose suppression test. If another long discussion for me to explain the reason why that's the case, but you can get false-positive results in dogs with iatrogenic Cushing's disease so you do NOT want to use a low-dose dexamethasone suppression test in this dog, at least as your initial test.