CUSHING’S SYNDROME

The “Not So Common” Drug Therapy

          My last article discussed the “common” drug therapies used in the United States to treat Cushing’s Syndrome.  This month’s article is going to focus on the “not so common” drug therapy I chose for my golden retriever, Boomer.  Not so “common” at this point in time!!  But with the success that Boomer has had, I can only hope that sooner or later it will be “THE” drug therapy for Cushing’s here in the United States !  I call it “Boomer’s Wonder Drug”.

What is the drug? Its name is Vetoryl®, active drug: Trilostane a/k/a Modrastane

          When Boomer was first diagnosed with Cushing’s (PDH/Pituitary Dependent Hyperadrenocorticism) in June of 2003, at the tender age of 9, everything I read said “life expectancy” from diagnosis and start of treatment, on “average” was 2 years!  I was NOT ready for only 2 years left with him!  I did my homework, researched the drug therapies being used in the United State and at first, hit a brick wall!  The common drug therapies just didn’t sound good to me.  Too many side effects reported, too many dogs “crashing”.  The road and direction I was being urged to travel did not bode well.  Yet, I knew I had to do something to help my boy!  I considered treating him holistically and on the chance of getting some reassurance and guidance, I joined a Cushing’s listserv. I am forever thankful that I did!  I do not mean to imply the members were or are giving out veterinary advice.  Not at all.  They simply introduced me to  “Boomer’s Wonder Drug”.  Vetoryl®, (active drug: Trilostane) is relatively a “new” drug that has, after a few years of clinical trials, become the drug of choice in the UK and with great success! 

From my research, I learned that clinical trials were done in a study at the Royal Veterinary College in London , the Veterinary Teaching Hospital in Dublin and Small Animal Hospital in Glasgow . The efficacy and safety of trilostane in the treatment of 78 dogs with confirmed PDH Cushing’s was monitored for 3 years. The starting dose varied from 1.8 to 20 mg/kg (mean = 5.9 mg/kg).  

It was found that trilostane was well tolerated by almost all dogs.  Unfortunately, as sometimes happens during clinical trials, there were a few deaths reported; however, even with the deaths, the low prevalence of side effects compared to those reported with mitotane (Lysodren) was promising.  The reports of “mild” side effects were what drew me to trilostane.  I did not want to subject my dog to any more “risk” than necessary. 

The results of the study showed trilostane to be nearly as effective as mitotane in resolving the signs of hyperadrenocorticism.  Excess water intake, frequent urination and extreme hunger dissipated in 40 dogs within 3 weeks after starting trilostane.  Within 2 months, a further 20 dogs showed decreases in their water intake/output and food consumption/hunger dissipated.  These improvements were maintained as long as the dogs remained on adequate doses of trilostane.   Skin changes resolved in 24 out of 39 (62%) of dogs that initially presented with dermatological signs.  Again, all of these improvements were maintained as long as the dogs remained on adequate doses of trilostane.  Only 8 dogs that were treated with trilostane for more than 2 months showed poor control of clinical signs.   The current suggested starting dose for dogs with PDH (pituitary dependent hyperadrenocorticism) Cushing’s is 5-10 mg/kg once daily.  (Kg equals 2.2 pounds)

Even with trilostane’s mild side effects, monitoring the clinical and biochemical effects of therapy is necessary and dosage adjustments do need to be made to achieve optimal control.  Dogs are to be re-examined and an ACTH stimulation test is to be performed at 10 to 14 days, 30 days and 90 days after starting therapy.  Boomer was started on a daily dose of 120 mgs divided into 2 doses of 60 mgs given every 12 hours.  While his starting dose was the recommended dose, it was “my” choice after conferring with the vet’s at Arnolds to split the dose in half.  After 10 days, we performed his first ACTH Stim Test and his “pre” and “post” cortisol numbers were down but not yet into the “normal” range.  After discussions with his vet and a few emails back and forth between Dr. Laura at Arnolds , we decided to “stay the course” and continue to treat conservatively.  Two weeks later, Boomer’s ACTH Stim again showed his numbers were again going down.  We were making progress! 

In late September, approximately 3 months into the trilostane therapy, Boomer’s pre-test and post-test numbers were right where they should be!!  Yahoo!!  As the months passed, Boomer’s clinical signs kept improving and by late November, I had my boy back!!  Boomer is now on a regime of 60 mgs every other day.   His water intake is normal, as is his “water” output!  His muscle tone has returned.  No more skeleton head!  His coat is thicker than it has ever been in his life!  He is playful and happy again!  This in turn makes me very, very happy! 

Trilostane has been available in 60 mg capsules in the UK since late 2001 under a temporary veterinary product license as Vetoryl® C. It is also available in 60 mg capsules approved for human use as Modrenal® from Masters Marketing in the UK . 

* Arnolds ’ (Arnolds Veterinary Products, the company who developed Vetoryl®, (active drug: Trilostane) veterinary advisor Francesca Gordon explains: “Not only is Vetoryl® a highly effective treatment for dogs with Cushing’s Syndrome, it offers significant advantages over the current treatment, mitotane (Lysodren®). Firstly, it is much easier to obtain - you just order it like any other drug from your usual wholesaler. Also, Vetoryl’s® effect on cortisol production is rapidly reversible, making it a less hazardous drug to use and one that is more readily adapted to the needs of each case. The ease and flexibility that Vetoryl® brings to the treatment of Cushing’s disease in dogs, is a real breakthrough.”

As with any medication minor side effects are sometimes seen.  These might include mild lethargy and decreased appetite 2-4 days from start of therapy (potentially due to steroid withdrawal syndrome) and mild electrolyte abnormalities. Overt hypoadrenocorticism seems to be a rare event despite the marked decrease in serum cortisol values found shortly after trilostane dosing.  Boomer has had NO side clinically visible side effects!

**In order to import the drug (Vetoryl) into the US , you must have an FDA waiver and/or a prescription from your veterinarian.  It can, however, be imported from Masters Marketing without the FDA waiver.  Visit their website listed below for more information.

In conclusion, if your dog is ever faced with the diagnosis of Cushing’s Syndrome, do him a favor and do some research into “Boomer’s Wonder Drug”…… Vetoryl®, active drug: Trilostane a/k/a Modrastane!!  Of course, always seek veterinarian guidance on health issues before treating any illness. 

For more information please visit www.arnolds.co.uk/NewsPage and http://www.mastersmarketing.com/home.htm 

As always, the above information is based on my personal research and first hand experience with my golden retrievers.  My reference for the medical/technical information for this article is: Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism.
Neiger R, Ramsey I, O'Connor J, Hurley KJ, Mooney CT. and information taken from www.arnolds.co.uk/NewsPage/ 

My next article will focus on the “holistic” approach to treating Cushing’s Syndrome.  Until then, I can be reached at boomer@trianglenet.net.  Comments and/or questions welcome!

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