Q & A: Trilostane Treatment of a Cat with Cushing's Disease

Rickie is an 9-year old, male-neutered DSH weighing 5.9 kg that presented for weight loss despite a voracious appetite and poor hair coat. Routine blood work showed a moderate hyperglycemia (serum glucose, 250 mg/dl; reference range, 70-150 mg/dl), Complete urinalysis showed a specific gravity of 1.050 and 3+ glucosuria.

We switched him to a low carbohydrate/high protein diet (Purina DM) and rechecked him again in 2 weeks. At that time, he had gained almost a pound and was not polyuric or polydipsic. His repeat serum glucose concentration was normal at 110 mg/dl.

The owner continued to monitor his blood glucose concentrations at home and got readings between 100 to 200 mg/dl. He continued to maintain his weight, but the owner remained concerned about his voracious appetite (tearing into food bags, etc.) and the thinning of his coat.

In the hospital, a blood glucose was measured at 220 mg/dl with 3+ glucosuria. He had lost his black outer coat with only a soft brown undercoat remaining. He had lost the hair around his neck (where his collar rubs) and on his belly. He had a pendulous abdomen with muscle atrophy most noticeable on his spine. The skin appears fragile and thin.

So we ran an low-dose dexamethasone suppression test (0.015 mg/kg, IV). The results were as follows:

• Baseline cortisol was 5.5 μg/dl (reference range, 2-6 μg/dl)
• 4 hour post 4.2 μg/dl (reference range, 0-1 μg/dl)
• 8 hour post 4.2 μg/dl (reference range, 0-1 μg/dl)

At least to me, these results appear consistent with Cushing's disease. I'd like to start Rickie on trilostane (Vetoryl; Dechra Veterinary Products) at a dose of 10 mg BID, and then do an ACTH stimulation test in 2 weeks. Do you agree?

Is there anything else you'd recommend?

My Response:

First of all, Cushing's is a rare disorder of cats, with less than 100 cats ever reported. As in dogs, most cats have the pituitary-dependent form of hyperadrenocorticism, but cortisol-secreting adrenal tumors also occur in cats with some frequency (1,3). Many of these cats develop mild diabetes secondary to insulin resistance. With treatment of the hypercortisolism, the diabetic state may be reversible in cats with Cushing's syndrome.

What dose did you use for the LDDST? We have previously shown that the low doses of dexamethasone used for the test in dogs (0.01-0.015 mg/kg, IV or IM) gives us a high prevalence of false-positive test results in normal cats or cats with nonadrenal illness (3).

Because of that, in cats we use a much high dexamethasone — 10 times higher or 0.1 mg/kg, IV or IM — for the dexamethasone screening test in cats. So if this wasn't the dexamethasone dosage you administered for your LDDST, I would start by repeating the test to confirm the diagnosis.

I'd also recommend that you do a complete urinalysis and culture, if that has not recently been done. Many of these borderline diabetic cats with Cushing's syndrome will have "occult" urinary tract infections. If not detected and treated, these cats can go on to develop renal disease.

Followup and More questions:

For my LDDST, I did use the dose of 0.015mg/kg IV, so that was too low a dose for the dexamethasone screening test in cats. We repeated the test using the dose that you recommended (0.1 mg/kg), and the results are as follows:

• Baseline cortisol was 6.5 μg/dl (reference range, 2-6 μg/dl)
• 4 hour post 3.9 μg/dl (reference range, 0-1 μg/dl)
• 8 hour post 7.3 μg/dl (reference range, 0-1 μg/dl)

Those results appeared to be diagnostic for hyperadrenocorticism, so we did go on to perform an abdominal ultrasound. Result of the abdominal ultrasound showed two large adrenals (twice normal size according to the radiologist). So the finding of lack of cortisol suppression on the dexamethasone screening test plus the ultrasound findings of bilateral adrenal enlargement seems to point to pituitary-dependent hyperadrenocorticism (PDH.

Rickie's urine culture, collected on a urine sample at time of the ultrasound, was negative.

I'd like to start the Vetoryl at 10 mg, BID. Do you agree with my diagnosis and treatment plan? I appreciate your help and any other guidance you can give.

My Response:

Yes, I would agree that these test results are consistent with PDH. And I would definitely agree that you should start the Vetoryl now. This is a fat-soluble drug so it's important to give each dose with food. Hopefully that will help control his propensity toward diabetes as well as control his hypercortisolism.

We don't really know how exactly to monitor trilostane treatment in cats, but it does appear to be the medical treatment of choice for cats with hyperadrenocorticism (4,5). in general I do it the same way as we do in dogs. So in 2 weeks, I'd do the first recheck, getting a carefully history and performing a good physical examination. Additional rechecks should be done in 1 month and then every 3 months while on treatment with the drug.

I like to repeat the ACTH stimulation test on that day also, starting the test 3-4 hours after the morning trilostane capsule was given. In general, I aim for basal and post-ACTH cortisol results between 2-5 μg/dl; but again, we don't have tons of data to show how we should use this drug to treat cats with PDH.

Followup and More questions:

Rickie started the Vetoryl 5 days ago (10 mg, BID). Overall, he is acting fine, but the owner has noticed a definite drop in his appetite. He had to be called for a meal and didn't finish his dinner last night.

Would you change the dose or do anything different, or hold the line and do the ACTH stim as planned in another 9 days? This is definitely a change from a cat who would tear through bags to get at food and always had a good appetite even prior to his Cushing's disease.

My Response:

This is not a good change, and it may be a reaction to the drug. I'd lower the Vetoryl dose to 10 mg once a day, and continue to monitor the appetite. Keep me posted.

Followup at 1 month on trilostane (Vetoryl):

Rickie has been doing really well at the 10 mg trilostane once daily for the past few weeks. He's acting much more his normal self—still hungry and eager for food but not so voracious. I did a recheck this week and his basal and post-ACTH cortisol concentrations were 4.1 and 4.9 μg/dl, respectively. His serum chemistry panel was relatively normal, with a glucose level of 155 mg/dl.

We are continuing the same dose and plan to recheck him again in 2 months.

Followup at 3 months on trilostane (Vetoryl):

Best of all, he's growing in new black hair along the collar line and on his front feet where the skin was bare. The hair is also coming in nicelyon his belly where it was shaved!

We ran an ACTH stimulation test this week (125 μg Cortrosyn, IV) 4 hours after the morning Vetoryl dose. The basal cortisol concentration was 2.7 μg/dl and the post-ACTH cortisol level was 3.1 μg/dl, so we appear to be in the right range. Results of a CBC and serum chemistry panel were relatively normal. His serum glucose concentration is normal at 122 mg/dl. So, clinically he's definitely improved and doing very well.

References:

1. Duesberg C, Peterson ME: Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 27:321, 1997.
2. Peterson ME: Feline hyperadrenocorticism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Third Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, pp 205-212, 2004
3. Peterson ME, Graves TK: Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat. Research in Veterinary Science 44: 38-40, 1988
4. Neiger R, Witt AL, Noble A, et al: Trilostane therapy for treatment of pituitary-dependent hyperadrenocorticism in 5 cats. Journal of Veterinary Internal Medicine 18:160, 2004
5. Skelly BJ, Petrus D, Nicholls PK: Use of trilostane for the treatment of pituitary-dependent hyperadrenocorticism in a cat, Journal of Small Animal Practice 44:269, 2003