Comparing therapies for canine hyperadrenocorticism - DVM
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Comparing therapies for canine hyperadrenocorticism


In the United Kingdom, trilostane is officially registered for use in dogs under the trade name Vetoryl. The product for use in humans is listed as Modrenal. The current recommended initial dose is 30 mg once daily for dogs that weigh 3 to 10 kg; 60 mg once daily for dogs weighing 10 to 19 kg; 120 mg for dogs that weigh 20 to 40 kg, and 120 to 240 mg for dogs weighing more than 40 kg.

Re-evaluations are suggested after one, three, six and 13 weeks, and then after six and 12 months. Each re-check should include a history, physical examination and an ACTH stimulation test. The ACTH stimulation test should be completed two to six hours after administration of the trilostane. The target range for serum or plasma cortisol concentration should be between 1 and 2 mcg/dl.

It is readily apparent that these dose recommendations result in tremendous dose disparity among dogs. A dog that weighs 3 kg, being given 30 mg once daily, receives 10 mg/kg, while a dog that weighs 20 kg receiving 120 mg would receive 6 mg/kg. A dog that weighs 40 kg could receive as little as 3 mg/kg. These dose disparities can result in severe negative side effects.

Experience at UC-Davis differs quite a bit from that in the literature and the United Kingdom. It is not clear why the results have not been similar. It seems that the most common reason for choosing this drug over o,p'-DDD is safety. In other words, trilostane has been viewed as much safer and, perhaps, more effective in controlling clinical signs of pituitary-dependent hyperadrenocorticism.

Some of the dogs we have treated have done remarkably well on a once-daily protocol. However, a significant percentage of dogs we have treated with trilostane have become ill (including deaths), either from glucocorticoid deficiency or from glucocorticoid and mineralocorticoid deficiency (hypoadrenocorticism). Some of the iatrogenic hypoadrenocortic dogs appear to have this condition permanently. In addition, treated dogs that fail to exhibit resolution of polyuria despite having ACTH stimulation test results within the recommended range do occur.

Therefore, trilostane is neither more effective nor safer than o,p'-DDD. Of greatest concern is that trilostane has been less predictable regarding underdose, overdose, resolution of signs or need for dosing more often than once daily.

The UC-Davis current recommendation is to initiate trilostane therapy at 1 mg/kg once daily. That dose is continued for about one week until a veterinary re-check can be completed.

Owners are instructed to collect a small urine sample from their dog before leaving home the morning of the scheduled re-check prior to trilostane administration. Trilostane should then be given and the dog should be seen by the veterinarian two to three hours later.

The goal of therapy is an owner who is completely pleased with the response. As aids in achieving this goal, both urine and blood tests are indicated. The urine should be checked, at a minimum, for specific gravity, glucose and urine cortisol-to-creatinine ratio (UCCR). An ACTH stimulation test should be started at the time the dog is seen, again about two to three hours after trilostane administration.

The UCCR result should be within the reference interval and the post-ACTH serum cortisol concentration should be between 1.5 and 5.5 mcg/dl.

If the serum-cortisol concentration is within that goal and the UCCR is abnormal, the medication should be given BID. If the serum-cortisol concentration is too high, the trilostane dose should be increased. But if the serum-cortisol concentration is too low, the dose should be decreased.

This approach should be used at each re-check until the dog is doing well.

Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small-animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail:


Source: DVM360 MAGAZINE,
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