Q & A: Adjusting the Trilostane Dose in Dogs with Cushing's Syndrome: Blunted Cortisol Response to ACTH Stimulation

I am using trilostane (Vetoryl, Dechra Animal Health) to treat a 14-year old, MC Poodle (10 kg) with pituitary-dependent Cushing's disease.  He has also been diabetic for the past year. 

Prior to diagnosis of the Cushing's disease and treatment with Vetoryl (10 mg, BID), his diabetes was difficult to control and he was slightly insulin resistant. Now that he is on treatment for the Cushing's disease, his diabetes is well controlled with NPH insulin (7 U, BID). 

It is now 3 months since we started this dog on Vetoryl.  His 30-day recheck was good, with a basal cortisol of 2.0 μg/dl and a post-ACTH cortisol of 5.2 μg/dl. 

On his 90-day recheck, the dog looks great and the result of his CBC, serum chemistry panel and complete urinalysis look good. Results of the ACTH stimulation test, started 4 hours after the morning dose of Vetoryl, revealed a basal cortisol of 3.8 μg/dl, with a post-ACTH value of 4.0 μg/dl. 

I am concerned about the blunted cortisol response to the ACTH injection, more than the absolute numbers. What do you think? Should I lower the dose of the Vetoryl?

My Response

Do not worry about this dog's blunted serum cortisol response— this is a perfect response for a dog on Vetoryl.

As long as both the basal and ACTH-stimulated cortisol concentrations are above 2 μg/dl and the dog is doing well clinically, you should not be concerned about the lack of cortisol response to ACTH stimulation (1,2). In fact, even if the post-ACTH cortisol concentration was lower than the basal cortisol (but both were greater than 2.0 μg/dl), I would still not be concerned.

If all continues to be well, I'd follow-up with another recheck in 3 months. At each recheck, I would recommend at least a serum chemistry panel, urinalysis, and cortisol determinations (1,2). If no signs of relapse are apparent, you might want to monitor only a basal cortisol concentration (3), but I would recommend that you perform an ACTH stimulation test at every other recheck visit at the minimum.

Remember that dogs with either Cushing's disease or diabetes are predisposed to developing urinary tract infections (1), so I also recommend doing a urine culture every 6 months on these dogs with concurrent diabetes and Cushing's syndrome. These dogs can have asymptomatic urinary tract infections, so the urine culture should be done even if they do not show any overt clinical signs of hematuria or stranguria.

References:

1. Melián C, M. Pérez-Alenza, D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010; pp. 1816-1840.
2. Ramsey IK. Trilostane in dogs. The Veterinary Clinics of North America Small Animal Practice 2010;40:269-283.
3. Cook AK, Bond KG. Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism. Jornal of the American Veterinary Medical Association 2010;237:801-805.