Daphne (couldn't tolerate Trilostane) now rests in peace

[AvileeG]

Hello everyone – I am new here and looking for a voice of experience…

Daphne, our 12-1/2-year-old small-dog mix (Shih tsu? hairy hairless Chinese Crested?) was definitively diagnosed with Cushing’s over the summer (we had tested her three years ago, but both the ACTH Stim test and the ultrasound were borderline/inconclusive, so we did not start treatment at the time. She has been on insulin for the past three years for diabetes, assumed to be secondary to the incipient Cushing’s).

We started her on trilostane at the presumably low dose of 1 mg/kg (compounded to 5 mg/ml, so for an 11 pound dog, 1 mg/kg = 1 ml), BID, three weeks ago -- she had a fairly severe reaction after two doses, extreme lethargy (nearly immobile) and trembling/shaking, so we took her off for a day and restarted at half the dose; after one dose at 0.5 ml, she again had a severe reaction. She had been taking a Chinese herb to help with the incipient disease since three years ago, which we figured might have been interacting with the trilostane, so we discontinued the herb, waited a week, and then started again – figuring she is just exquisitely sensitive to this medication, so starting really low. We were shooting for one-quarter of the original dose, but creeping up to it by tiny bits – we started at 0.05 ml and planned on adding 0.05 / day until we got to 0.25 ml (BID).

We ended up going a little slower, because her blood sugar was affected more than we had anticipated, but other than that she had no bad side effects – until yesterday, her second day on 0.2 ml, when she began to have nosebleeds. They would not last very long (fortunately) -- not even long enough to get an ice pack to her nose before they stop on their own -- but in the last 24 hours she has had five nosebleeds, which is something she has never had in her life.

Other than that she seems fine – energy level is pretty good (as good as it gets, considering how much the Cushing’s has wasted her muscles), no appetite problems; only one odd effect of smelling like garlic.

So – what I wonder is if the nosebleeds are something that we could attribute to her body adjusting to the trilostane? Or is it something associated with Cushing’s? Right now we’ve temporarily discontinued the trilostane, because we’re afraid of the nosebleeds getting worse, and we’re waiting to hear back from the doctor… but I would love to know if anyone out there has had any experience with this symptom. (and if you’ve experienced this weird garlic smell, I’d love to know, too).

thank you for any advice!

[labblab]

Hello and welcome to you and Daphne, although I am very sorry for the problems that have brought you here to us. I wish I could offer some answers as to what might be causing these new issues, but neither nosebleeds nor a garlic odor are common or even known reactions to trilostane of which I am aware. A possible link between nosebleeds and Cushing's itself would be high blood pressure -- hypertension can result from effects of elevated cortisol, and hypertension can cause nosebleeds. I have no idea what could be causing the garlic odor.

But it does seem awfully coincidental that all of Daphne's ill effects have coincided with the new trilostane treatment. In honesty, I am a bit worried there may be a problem with your compounded med. I am wondering whether perhaps there is a mistake in the base chemical that was used, or in the concentration, or in some contaminant. I definitely would not give her any more of the liquid at this point. And these reactions are odd enough that if they should worsen -- especially the nosebleeds -- I believe I would seek emergency care if your own vet is not available. Can you check her gums to see whether they seem pink and healthy, or are they blue or mottled in any way?

Is there any chance at all that Daphne could have gotten into any type of poison (like rat or insect poison?). Some of those poisons act by disrupting blood coagulation, and the combo of the nosebleeds and the odd garlic odor would have me worried about that possibility, as well.

Please do update us as to how she's doing, and I certainly hope you'll hear back from your vet promptly.

Marianne

[mytil]

I do agree with Marianne - it could be a coincidence about the Trilostane and the sudden onset of nosebleeding and the garlic odor.

I would seek immediate attention for your pup.

There are numerous things that can poison a dog and cause nosebleeds and the smell of garlic in a garden. Possibly there is something in your garden that contains arsenic (like slug and snail baits and even ant bait).

Please keep us posted
Terry

[labblab]

Terry, now that you mention it, I am wondering about arsenic, too, because it does have a garlic odor and could also cause all the initial problems that Daphne experienced. Thanks for mentioning that!

I wonder if there is any chance that the the compound liquid could be contaminated with it, because the timeline sort of makes sense. There were acute problems when the dose was higher, and then subacute problems that manifested more slowly at the lower dose. I think that's kind of the way that arsenic poisoning works.

For sure I would not give any more of the liquid right now and I would keep it on hand for the possibility of lab analysis if need be.

Marianne

[mytil]

At least it should be looked at. Unfortunately, arsenic is also found in "trace amounts" in a lot of poultry etc under the name of 3-Nitro (Pfizer agreed to withdraw it from the market just this year). http://www.fda.gov/AnimalVeterinary/.../ucm257540.htm.

Please let us know where is your Trilostane compounded! I would contact them to see what the ingredients of the suspension are.

Please keep us posted

Terry

[Squirt's Mom]

How is Daphne this morning? I am worried along with others, concerned this might be a case of poisoning. Praying she is much better!

[AvileeG]

Hello everyone,

Wow! I did not expect so many responses so fast! As it happens, our regular vet clinic returned our call too late to bring her in, so we took her to the emergency clinic. Her bloodwork checked out fine (although her AlkPhos was higher than a couple of months ago, so the Cushing's is apparently progressing). The emergency doctor was quite thorough, talked with us for quite some time, and did not have any specific answers after the diagnostics other than that is is not end-stage liver failure (which she sometimes sees associated with nosebleeds), and apparently not poison since her RBS and WBS were normal. She did mention the possibility of her throwing clots, associated with Cushing's, but that the nosebleeds are not the way that would manifest ordinarily.

As of this morning, she had one more nosebleed at 2:00 am (10 hours ago now) and not since (am am touching wood as I type this). She has had no trilostane since Thursday evening, and we re-started her Chinese herb for Cushing's support (Si Miao San) in case discontinuing that had anything to do with this. So we are watchfully waiting to see if she has any more problems...

There is no possibility she could have ingested anything poisonous in our garden or house, we keep no toxics anywhere (she has also been on an organic, home-cooked diet all her life, low-glycemic for the past 3 years of course). The compounding pharmacy we use has been very dependable for us for many years -- we have used them for the postassium bromide our epileptic dog took years ago, as well as Calitriol and Methimazole for our cat -- all with no problems at all. However, they do often flavor the medications to appeal to non-humans, and this is the first time we have ever gotten anything with duck flavor (the kitty always had tuna flavor)... So the information about arsenic smelling like garlic is definitely interesting, and I wonder if the duck flavor might be the culprit.

The first two times she reacted to the trilostane, it definitely appeared as an overdose, heading-toward-Addison's reaction, with very high potassium and low sodium along with lethargy and trembling -- but I wonder if that may have masked something else going on.

At any rate, she appears to be recovering (except for the progressing Cushing's of course)... We are going to keep her off the trilostane for a while, and not restart until we can contact the pharmacy to have them test their flavorings and other ingredients.

thanks so much for all your advice and support!
Avilee

[AvileeG]

A bit of an update -- we spoke to the doctor at the emergency clinic who did the bloodwork, and she was pretty emphatic that it showed no toxicity. So now I'm very confused about this garlic smell, and where it is coming from...

Meanwhile, she has had only a couple of extremely brief and mild nosebleeds (a few drops, when getting really excited about eating) since the one at 2:00 this morning -- compared to fairly significant bleeding every 3 - 4 hours the day before, so it does seem to be abating. The garlic smell is also diminishing, though not gone (mostly garlic-smelling gas). So it is all very puzzling...

[molly muffin]

That is very strange. I would make sure that the nose bleeds have completely stopped before introducing trilostane again. Nose bleeds though are not usually associated with trilostane or cushings that I have noticed.

What did the emergency vet say she thought might be causing it?

[Squirt's Mom]

I would be pursuing the compounding possibility with all my power if I were you.