Protocol for ACTH Stimulation Testing to Monitor Dogs on Trilostane Therapy: Timing, Feeding, and ACTH Preparation All Matter

I have a question about the use of ACTH stimulation testing in dogs we are monitoring on Vetoryl (trilostane) therapy.  When we recheck these dogs, when should the ACTH stimulation test be started after the morning dose of the drug is administered? 

In other words, how many hours should we wait after giving the morning medication and starting the ACTH stimulation test?  I've read anywhere from 3 hours up to 6 hours?

We normally fast our dogs overnight before any cortisol testing. Should the dog be fed or fasted the morning of the ACTH stimulation test?

My Response:

Most of the initial studies recommended that the ACTH stimulation test be done 4-6 hours after dose administration times, but more recent investigation indicate that the drug generally has a peak effect earlier (1). I like to have my dog owners make the appointment at 2-4 hours because this interval ensures that we are testing at close to the peak effects of the drug (2).

Four important points here:
First, trilostane should always be given together with food. It has been shown that feeding immediately after the administration of the drug significantly increases its absorption (1,2).

Second, It's very important to be consistent in timing when using ACTH stimulation test to make dosage adjustments. We don't want to start one test at 10 AM, then do the next follow-up ACTH stimulation test at 2 PM and compare the results. Because of the relatively short-acting effects of trilostane, the results of ACTH stimulation testing varies considerably with the time of testing relative to dosing.

Third, when we state that the ACTH stimulation test be done 2-4 hours after the morning dose, that's when the basal serum cortisol is collected and the ACTH injected.

Fourth, the form of ACTH injected makes a difference. If synthetic ACTH (cosyntropin or Cortrosyn) is used, the post-ACTH cortisol sample is usually collected at 1 hour after ACTH administration. If the ACTH preparation used is a gel, the post-cortisol sample is usually collected at 2 hours.

• If we use ACTH get and start the test at 4-6 hours after the morning dose, we have a good chance of missing the time of the peak action of trilostane.  Remember that after administration of trilostane, peak concentrations are seen within 1.5 hours and decrease to baseline values in about 18 hours (less in some dogs). 
• In addition, many of the ACTH gel products are formulated by compounding pharmacies, and these may not always be reliable (3).
• For these reasons, I prefer using synthetic cosyntropin over ACTH gel when doing an ACTH stimulation test to monitor trilostane therapy.

Bottom Line:  

1. When monitoring dogs on Vetoryl (trilostane) for Cushing's disease, start your ACTH stimulation test 2 to 4 hours after the morning dose of the drug has been administered.
2. The dog should never be fasted on the morning of the test. Trilostane is a fat-soluble drug and must be given with food to help increase its absorption. 
3. Ideally, use synthetic cosyntropin to do the ACTH stimulation test to ensure consistent and reliable results.

References:

1. Melián CM, Pérez-Alenza D, Peterson ME. Hyperadrenocorticism in dogs In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat  (Seventh Edition) Philadelphia, Saunders Elsevier, pp 1816-1840, 2010.
2. Ramsey IK. Trilostane in dogs. Vet Clin North Am Small Anim Pract 2010;40:269-283. 
3.  Kemppainen RJ, Behrend EN, Busch KA. Use of compounded adrenocorticotropic hormone (ACTH) for adrenal function testing in dogs. J Am Anim Hosp Assoc 2005;41:368-372. 

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