Calcinosis Cutis and Trilostane

[lulusmom]

I will be posting this on four members' threads, all of whom are dealing with calcinosis cutis. Kerry, Millie's Mama; Crystal, Annabelle's Mama; Shelly, Lucy's Mama and Pat, Peety's Mama.

I've seen too many dogs on Trilostane who have either had little to no effect on Calcinosis Cutis or a worsening effect while on the drug. Based on the frequency with which we've seen calcinosis cutis on this forum, there seems to be a correlation with the increased popularity of Trilostane for treatment of cushing's. I've had a gut feeling for a very long time that Trilostane is responsible for worsening calcinosis cutis due to it's effects on the sex hormones. Dr. Oliver, was the leading expert on adrenal steroids and he firmly believed that 11-deoxycortisol levels build-up in dogs being treated with Trilostane as did other intermediate steroid such as androstenedione, 17-hydroxyprogesterone, estradiol and progesterone. I've never been able to find anything in layman's terms that explains the affect, if any, these steroids have on calcium metabolism. While searching for that connection, I stumbled upon something even better. It was an abstract of a study entitled, "Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations". The last sentence of that abstract was eye opening.

[B]Despite no significant difference between calcium concentrations in the pretreatment HAC and control groups, calcium concentrations increased significantly with treatment....and....These results show that adrenal secondary hyperparathyroidism resolves with treatment and suggest that increased calcium and phosphate levels have a role in its pathogenesis./B]

It looks to me that cortisol isn't the only adrenal steroid that can cause elevations in blood calcium levels. Dr. David Bruyette, a renown endocrine expert, readily admits that he has had bad luck in resolving cc with trilostane. That's pretty telling coming from a high profile specialist who is a contributor to Dechra's continuing education program for veterinarians. This is not a new study. As a matter of fact, I believe it may have been published before Vetoryl was approved by the FDA.

You can find the complete abstract here: http://onlinelibrary.wiley.com/doi/1...283.x/abstract

I'm just sharing my thoughts with those of you who may want to start asking more questions of your vets....or you may even consider calling Dechra, the manufacture of Vetoryl (Trilostane). I'd be very interested to hear what they have to say about this study.

Glynda

[labblab]

Glynda, this is a really interesting study, that's for sure. I hope you don't mind, but I've placed a copy of your post here so that we have one consolidated place in which to post general replies so as to avoid having to repeat them on each of the four separate members' threads. I'll come back in a little while to add some thoughts of my own.

Marianne

[labblab]

OK, I'm back with a few thoughts to add. I'm really interested in tracking down this study and reading it myself. Good find, Glynda!

I definitely agree with you that we've recently seen a huge increase in the number of dogs presenting with Calcinosis Cutis. But my own memory is that the majority have come to us prior to any treatment at all. In fact, it is the CC that is contributing to the Cushing's diagnosis in the first place. I believe three of the four dogs in whose threads you earlier posted all exhibited CC before they began treatment. I think Annabelle is the only one who has developed initial skin problems subsequent to treatment. My memory may certainly be wrong, but I think it remains somewhat unusual for us to see a dog who has been stabilized on trilostane to subsequently develop CC for the very first time later on down the road.

So that leads me to believe that there is some other unrelated mechanism that is increasing the incidence of CC, or perhaps vets are just becoming more knowledgeable and/or vigilant as to their awareness that skin issues may warrant a speciality derm referral or a Cushing's work-up.

Now as to whether trilostane helps/hinders the resolution of pre-existing Calcinosis Cutis once treatment is initiated -- I think that's a different question, and this study may be very valuable in that regard.

Marianne

[spdd]

All I can say is "Oh Geez." I'll be watching for this in Keesh.

[Trixie]

I'm pretty relieved to read your assessment Marianne. So basically the cal cutis existed on all but one dog (on this forum) prior to the start of Trilostane?
I found myself starting to re-think the med choice if it was the Trilostane causing the ailment itself. So much scary stuff associated with this disease.

You all are amazing experts and researchers! This site has, by far, the most comprehensive Cushing's info bank on the internet. None of the sites for animal health or vet info has anything near what is on this forum!
The vet schools should all have their students on this site so they can learn a few things!

Thank you all for the time spent getting the word out on this board..it's helping so many people (and pups) in so many ways!

Barbara

[spdd]

Amen to that Barbara, and when I spoke to Dechra, I told them how often they are mentioned on here and they should take a look at the forum. She told me they try to stay away from here... their loss.

[labblab]

I'm pretty relieved to read your assessment Marianne. So basically the cal cutis existed on all but one dog (on this forum) prior to the start of Trilostane?

Barbara

Hi Barbara, the four dogs I mentioned are four currently active members who are battling CC, and on whose threads Glynda had earlier today posted the info about the study result. And yes, I think that of those four, only one developed CC subsequent to beginning trilostane treatment. Over the years, we have had additional dogs on the forum with CC, but we've suddenly seen a surge in the incidence of the disorder. So that is what is really prompting our special interest now.

I haven't gone back through our archives to review the status of all the other dogs with CC, but my memory is that the majority were already afflicted with CC prior to diagnosis/treatment. So that is why I'm doubtful that trilostane is to blame for the overall increased incidence that we're seeing.

If somebody had the time to do it, it probably would be interesting to go back through our archives and make note of all the dogs diagnosed with CC, whether the diagosis preceded treatment, which drug was used to treat the Cushing's, and whether or not the CC ultimately resolved satisfactorily.

A nice project for a rainy day, right????

Marianne

[Harley PoMMom]

If somebody had the time to do it, it probably would be interesting to go back through our archives and make note of all the dogs diagnosed with CC, whether the diagosis preceded treatment, which drug was used to treat the Cushing's, and whether or not the CC ultimately resolved satisfactorily.

A nice project for a rainy day, right????

Marianne

I am on vacation next week and I'll look into that.

[labblab]

YAY, Lori!!!!!!!!!!!!!

[Arizona Boston]

Glynda,

Thanks for your work on our behalf! Before these recent weeks of reading posts, I just assumed everyone's dog had Cutis.

I am racking my brain to remember the exact sequence...which came first, the Cutis or the Vetory. There may have been one crusty bump at the time of Lucy's diagnosis, but I couldn't swear to it. I will say this for sure, since the start of her Vetoryl therapy, the Cutis has really escalated, probably increasing by 5 % each month of her 9 months of treatment. It is the main reason we switched vets and why we increased her dose of Vetoryl from 30mg to 40mg.

I will have more info after we get her next ACTH 7/24. Then she will have been on the 40 mg dose for 3 weeks.
Shelly