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/SafetyHealth/ProductSafetyInformation/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. ;)

[Harley PoMMom]

Has her blood pressure been checked? High BP can cause nosebleeds.

[AvileeG]

Sorry, I've been off the forum for a week (dealing with school)... Anyhow --

Unfortunately, the emergency clinic doctor didn't have a definitive answer as to what could be causing the nosebleeds, She did rule out end-stage liver failure (apparently she sees that a lot when dogs are brought in with nosebleeds), and, quite confusingly, she ruled out toxicity. Meanwhile, the nosebleeds did stop (last Sunday was her last tiny one), so it seems awfully coincidental if it was not contamination in the trilostane, given that nothing else has changed other than discontinuing it (and that nosebleeds are not a known side effect of trilostane).

So now this leaves me wondering whether her earlier reactions, which really did look like trilostane overdose/severe steroid withdrawal, were actually due to contamination and she is not as incredibly sensitive to trilostane as we thought... We are seeing a new holistic doctor this afternoon (this whole incident comes in the wake of having lost our long-time, amazingly perceptive holistic doctor over the last half-year), so we'll see if she has any interesting insights.

Thanks so much for your concern, everyone!

[AvileeG]

Oops, I only saw that last question after I had already posted -- yes, her blood pressure was checked at the emergency clinic and came in perfectly normal. At any rate, she is well over them now.
Thanks again...

[AvileeG]

Hello everyone,
Since so many of you here have been so kind and concerned when I posted about Daphne's nosebleed crisis, I figured that now that crisis is ameliorated I ought to more generally introduce her to the forum. Sorry if this is really long, it's been a bit of a saga with her that I'm writing down all at once...

She is a now 12-½-year-old little dog, we have no idea what but we always assumed part shih-tsu or lhasa, lately thinking more toward hairy hairless Chinese Crested (her hair was always pretty thin, even before the Cushing's).

We started testing her for Cushing's in spring 2012, when her liver values started to rise (AlkPhos 890 in April, 1800 in July; ALT 140 in April, 244 in July), at the same time as she was drinking and peeing a lot and we noticed the pot belly. Both the SCTH Stim test and the ultrasound were borderline /inconclusive, so our vet was not ready to start treating her with the usual heavy-duty treatments. At the time, we had an amazing (and amazingly perceptive) holistic doctor (western medicine plus traditional Chinese medicine) who had treated all our babies for many years -- she started her on Si Miao San, hoping that would keep her mild, incipient pre-Cushing's at bay, as well as Denamarin to help her liver.

During that fall she lost a lot of weight while eating everything in sight, then her blood glucose spiked and she was diagnosed diabetic (presumed secondary to the incipient Cushing's) in December 2012, started on insulin January 2013. We started with just a half-unit and worked up from there, so it took a while to get her to her current dosage of 7-½ units, but once we did her liver values came down a lot (though not normal, sill a lot better -- AlkPhos in the 500s, ALT down as low as 99) and things stabilized for a couple of years. It was definitely a relief to see her gain the weight back and get some energy back once we got her blood sugar stabilized — although diabetes can definitely drive you crazy, we get a lot of good advice from our neighbor who is a type-1 diabetic.

In the summer of 2014, we noticed her liver values rising a bit, so our doctor added another liver-support herb, but we didn’t really see her symptoms progressing at the time. We do think now that probably the Si Miao San and other herbs managed to keep the pre-Cushing's at a low level for a while... It wasn't until early this year that we noticed how much her hair was thinning out, and that she was getting steadily weaker and weaker as her muscles deteriorated. This unfortunately coincided with our trusted holistic doctor having to give up her practice and move away (long story); we stayed with the the second doctor, who had also occasionally seen Daphne over the years, for our summer checkups. She took a look at her and advised us to have her re-tested for Cushing's, for which we are grateful (her ACTH Stim test came back 5.1 pre-stim, 30.5 post-stim, which combined with her now-accelerating symptoms looked like enough to start treating) -- but since she is not a holistic practitioner she couldn't advise us on the Chinese herbs and how they might interact with any conventional treatment.

We started her in late August on trilostane at the standard low dose of 1 mg/kg BID (easy, since she’s an 11 lb / 5 kg dog), compounded to 1 mg/ml because they were out of 5 mg pills. After two doses, she had an intensely severe reaction — shaking and extreme lethargy (nearly immobilized), so we stopped the drug for a few days, then restarted at 1/2 the dose (0.5 ml). This time she only had one dose before developing the same severe reaction; and this time we took her to the clinic where they tested her and found her electrolytes way off (potassium high, sodium low, what you might expect with too much trilostane). So we figured she was just immensely sensitive to this stuff...

The impression we got from the doctor was that it was trilostane or nothing, that Selegiline wasn’t even worth trying — and since she is aging fast with this disease, not treating her felt like just giving up on her. So we tried the trilostane again (after more than a week off, and after stopping the Si Miao San), starting at 0.05 ml to work up to 1/4 ml. We had gotten her up to 0.2 ml, seemingly fine — when on the 2nd day at that level she started having sudden and very frightening nosebleeds. We ended up taking her to the emergency room, where they did more blood tests but never found an explanation, aside from ruling out any toxicity.

We had stopped the trilostane, and the nosebleeds diminished and then stopped, about two days after they started... She did also have diarrhea (very severe at the time of the nosebleeds), which started about the time we started that last bout of trilostane.

So last week we did what we should have done months ago, and made an appointment with a holistic doctor recommended by our previous doctor. We saw her last weekend,and she advised us on some strategies for the diarrhea as well as how to go forward with treatment for the Cushing’s. She agreed with us that the nosebleeds must have had something to do with the medication — the timing was just too much of a coincidence — and that since the blood-work showed no sign of toxicity, even though nosebleeds are not a known side effect of trilostane, it is just too much of a risk to try it again.

So we are going to try Selegiline/Anipryl, along with a new herb formula for support. Although it feels a little odd to change doctors while we’re trying to deal with such a difficult disease process, the amount of time she spent with us, closely observing Daphne, felt much more like what we’ve been used to, and we feel like we made the right decision... I do so hope the Anipryl will work, I know it doesn’t with all dogs — but after that episode with the nosebleeds I would be afraid to try trilostane again even if the doctor recommended it (although, heartbreakingly, I did see some signs of increased energy with that extremely low dose). Right now we are still dealing with the lingering effects of the shocks to her system, with the diarrhea still very gradually improving — we would like to get her closer to her "normal" before starting a major new medication, but it looks like we are figuring on starting the Anipryl tomorrow or Saturday at least.

Again, sorry this is so long — thank you so much for reading this, if you've gotten this far!

[Squirt's Mom]

MODERATOR NOTE: I have merged your post giving more detail of her health history into Daphne’s original thread. We like to keep all posts about each pup in a single thread as it makes it easier for members, and parents, to refer back to the pup's history when needed. Thanks!

[molly muffin]

Those nosebleeds where very strange indeed.
Anipryl works in a small percentage of dogs so I hope that it helps Daphne.

Let us know how it goes.

[Squirt's Mom]

My Squirt used Anipryl with success for about 9 months - much longer than it usually works when it does. For Anipryl to have any effect at all, the pup MUST have the pituitary form of Cushing's (PDH) - Anipryl will do absolutely nothing for the adrenal based form (ADH). In addition, the tumor on the pituitary MUST be in the pars intermedia portion of the pituitary gland. 85% of cush babies have PDH; of that 85%, about 20-25% of those pups will find Anipryl is effective. We were extremely lucky with Anipryl that it worked as well as it did for as long as it did. Squirt was not the typical cush pup. ;) Because of our experience with this drug, I always support it's use tho many don't. In this case with the apparent sensitivity to the Vetoryl (Trilostane) I think trying the Selegiline (Anipryl) is worth a shot. If it works, it will give you a few months to look into other options.

Anipryl does have side effects. It can make them nauseated; keep Pepcid AC (NO OTHER FORM OF PEPCID) on hand as she may need that daily or another antacid approved by the vet. It can make the very restless, especially in the beginning - it is metabolized into something similar to speed in dogs. ;) But this aspect fades with use - digestive upsets do not. I am glad that her blood pressure was checked before starting this drug and recommend it be monitored after starting just in case. BP can spike causing problems yet be normal when checked - the spikes have to be caught. With the nose bleeds, the BP should be monitored anyway I would think to make sure there isn't something going on causing extreme spikes. ;) Here is a link on Anipryl - http://www.drugs.com/vet/anipryl-tablets.html

Unless you are in the UK, you do have another option - Lysodren. Some folk, including some vets, are afraid of this drug. But I am much more afraid of Vetoryl myself and will always choose Lyso first if faced with other cush babes. Lysodren has been around for a very long time and we KNOW what it is doing in the body. Vetoryl is the new kid on the block and we are still learning exactly what all it does and how to use it. BOTH drugs have the exact same warnings, up to and including death. Neither drug is safer than the other. BOTH are life-savers for our babies. It is not uncommon to find that a pup simply cannot handle one or the other and needs to switch. Some can't handle the Trilo, some can't handle the Lyso...but do wonderfully on the other when switched. ;)

Are you a member of our sister site, K9Diabetes? If not, go register. They are THE experts on canine diabetes. http://www.k9diabetes.com/forum/ That does NOT mean you get to leave us, tho - nope, not at all. You and Daphne are family now but we do want you to have the best of both. :)

Hugs,
Leslie and the gang

[AvileeG]

Hi Leslie,

Thanks so much for the link and all the other info... Daphne's ultrasound was consistent with PDH (plump adrenals on both sides), though of course we have no idea where the tumor is without doing some more extensive testing -- so we're crossing our fingers hoping the Anipryl will help given her absolute inability to tolerate trilostane (the doctor who originally prescribed it concurred that "this looks like a dog who just won't get along with trilostane"). So far so far -- she had her first dose this morning with no ill effects, and some evidence of increased energy (that speed effect, I imagine) -- on our walk today, she spontaneously broke out of "first gear" into trotting or galloping more than I've seen in a while without major encouragement, and we went farther than usual as well. No apparent nausea or appetite effects yet (though with this little girl, we figure the first time she really loses her appetite will be pretty near the end -- her food obsession long predates her Cushing's or diabetes ;)).

I guess my fear of Lysodren would be mostly with that initial loading dose -- especially now, given her history with such miniscule doses of trilostane. No matter at the moment, we're trying the Anipryl; but if it doesn't seem to be helping after the requisite couple of months, I guess I may start looking into whether it's possible to ease into lysodren (as we were trying to do with trilostane)...

I did know about the K9 diabetes forum, and registered and looked in on it a bit initially; but I haven't had many questions about the diabetes for a while because she has been pretty well-controlled since we got her up to her current insulin dose a couple of years ago. Although diabetes can drive you crazy, with seemingly random fluctuations in BG, we manage to keep her in or near her target range at her afternoon nadir at least most of the time... Our previous doctor (the holistic one who had to move away) was also very experienced with diabetes, plus we've had our neighbor to commiserate with. ;)

thanks again!
Avilee

[AvileeG]

Sorry it's been so long since I checked in here — things tend to get away from me once the school year gets rolling. Anyway...

Little Daphne is hanging in there since her experience with trilostane early in the fall — but we are only now, almost 4 months later, digging out from under the effects of that little adventure. (to recap, since it's been a while: we made three tries with trilostane, each about a week apart — once at the standard low dose (1mg/kg), once at half that, and the last time at 1/10 that... She went into apparent Addisonian reaction after only two doses the first two times, then started a frightening series of nosebleeds after only a few days of the 1/10 dose. Those nosebleeds (6 per day) are still unexplained, since they are not a known trilostane side effect — both our regular vet and the emergency clinic were emphatic that her bloodwork indicated no toxic exposure — but they did stop the day after we stopped the trilostane).

Meanwhile, she also developed a nasty case of diarrhea which took months to mostly resolve — it only really began to improve after we figured out that her body chemistry had shifted so that she is now allergic to both turkey and oats, two components of her diet for years. She is now on de-fatted duck and rice, and finally making progress, but not nearly back to normal. And of course she lost weight during the course of the diarrhea, which we are working to get her to gain back.. but this is not an easy prospect, complicated by the limitations in her diet, especially since she now seems to have long-term IBD and if we give her anything with a moderately high fat component the diarrhea comes right back.

Her blood glucose levels have also become wildly unpredictable — where we used to test her once a day at her afternoon nadir, we now have to test her six times a day (including 2:00 am) to catch her swings and keep her from spiking too high or, even worse, crashing into dangerous hypoglycemia. In all, it's been a difficult few months, from which we are gradually recuperating...

Meanwhile meanwhile... We started her on Anipryl back in October, in hopes that it might help as an alternative to harsher drugs. So far it doesn't seem to have done much — although she does seem to have stopped getting weaker, as she had been doing over the summer, so perhaps it has at least arrested the progression of the disease. We are giving it one more month (figuring that she was so sick with the diarrhea for much of the time she's been on it that it wasn't really a fair test) before we try doubling the dose to see if that will have any more visible effect.

So at this point it feels like we are pulling her out of a serious crisis, but we are pretty much back at square one with the Cushing's, with nothing that effectively treats it without half-killing her in the process. I have read here and elsewhere about the U of Tennessee protocol with melatonin and lignans, as well as phosphatidylserine — of course I've read that it is only effective as a starter for really mild cases, or for atypical Cushing's, or for a little extra support along with the usual meds; but I have to hope that maybe that, along with the Anipryl (and the Si Miao San she's been on for three years) can keep this thing at bay for a while... Because after her reaction to one-tenth of a low dose of trilostane, I am not at all ready to go down the road on an irreversible medication like Lysodren which has to start with a loading dose!

Right now, Daphne's quality of life is good — yes, she's pretty naked and hairless, but she does have a good collection of sweaters; and yes, she's a lot weaker than she used to be, but she can still climb the stairs and her energy on neighborhood walks is still good (and long hikes were never her great joy anyway -- that would be eating and visiting with people). After the crisis she's been through recently, I'm afraid of messing that up for her...

I guess I'm not really looking for any solutions here, since I don't see any really good ones out there. The good thing is that we now have an excellent new vet who works in both allopathic and alternative modalities — we will see her for another re-check in January and see if she has any insights on those supplements with her, and go from there... Just thanks for having this resource, and giving me the chance to write about this!

[molly muffin]

well I'm very glad to hear that Daphne is recovering from her terrifying crisis earlier this year.
I have to agree, that those nosebleeds certainly do seem to be tied to the trilostane based on timing. It is just not something we usually see, but they do say that every dog is different so nothing can be ruled in or out.

Did we mention before that pumpkin is great for diarrhea episodes. They now make pumpkin packets for dogs. It doesn't take much, like a teaspoon when you notice diarrhea starting. I also give foriflora probiotic which seems to help too.

Those unique proteins are essential with the IBD, although they can get pretty finiky about what they want to eat with it too from the ones on here who have gone through it. Rabbit, venison? Those might also be options.

Glad to see you back again. :)

[AvileeG]

Pumpkin, huh? Our neighbor told us about Japanese sweet potato for diarrhea, and we tried some of that for a while -- problem with that is that it's also a pretty effective (though gentler) sugar substitute for when she's going hypoglycemic... So feeding her too much of it could send her blood sugar through the roof! If pumpkins works with just a tiny bit that could help.

[molly muffin]

It's worth a shot. Most of us on here have or do use it.
You'll have to try a bit and see what it does to her blood sugar.


Pumpkin ranks high on the glycemic index, or GI, which suggests that the ... pumpkin may not cause a dramatic increase in your blood sugar.

So might be worth trying but I'd closely monitor to see how she reacts.

[AvileeG]

It's been a while since I was able to check in here — sorry I haven't been more active, I do so appreciate this forum being here and the information I find when I have the chance to look in on it — so, apologies for this being a bit long (and I guess the original title of the thread is obsolete, since nosebleeds have not been an issue for a long time...).

Anyway... After the brief experiment with Trilostane last fall, Daphne's health went into a fairly alarming decline for a few months — she has since stabilized to some extent, but we are still digging out from under that episode 10 months later. Although the nosebleeds stopped as soon as we stopped the trilostane, she was left with a nasty case of diarrhea, which resolved to something like low-grade IBD (soft poops and plenty of gas), but her digestive system has never managed to get back to normal and we had to revamp her diet to deal with it. The medication also played hell with her blood sugar and insulin response, and we are just now gradually getting her back to the fairly decent regulation she had had for a few years prior. In the meantime, her obvious Cushing's symptoms (hair and muscle loss) kicked into high gear after the trilostane trial — she went from very thin hair last August to nearly naked by January... In the five months since then she has not exactly improved, but at least she has held fairly steady. I think I had read on this forum, years ago, the advice that Cushing's dog guardians should periodically take photos in profile, to track the physical changes, so I have done that (is it possible to post some here?) — the changes in her physical appearance in the 5 months from August to January were frankly alarming, while the changes in the last 5 months were relatively minor.

So, given her atypical and severe reaction to trilostane, our doctor agrees that it would be quite risky to try lysodren, especially with the necessity of a loading dose (so not being able to try creeping up by miniscule amounts as we did with trilostane). We did try Anipryl for a few months, but it didn't do anything that we could see. So we are now in the realm of supportive and palliative care — she is on Cushaway and Si Miao San specifically to help with Cushing's support (Si Miao San was prescribed long ago by our excellent holistic vet, while Cushaway is the one "natural" remedy I have found with ingredients which actually have some legitimate research behind them), along with various herbals to help with her digestive symptoms and diabetes (and hefty doses of insulin, of course).

As far as her quality of life — her current weakness would have been pretty hard on her big brother, who was part kelpie and whose joy in life was exploring far and fast and finding any excuse to run; on the other hand, Daphne's raisons d'etre are hanging out with her human friends and eating, so as far as we can tell she is still a happy little girl as long as she gets plenty of lap time and good things to eat. She did go through a phase where walks got to be a chore for her — but since we took to carrying a handful of Cheerios and rewarding her every block or so, she has picked up the pace and seems to even be enthusiastic about walks again. So her life is pretty okay, at this point.

So, if I have any question about this, it would be — I understand that Cushing's is not in itself a painful disease, but I wonder what we might be looking at in terms of how this progresses... Sorry, I know this might be an unpleasant subject for those who have Cushing's dogs who have passed — but I guess a voice of experience would be appreciated. We have had dogs who died of cancer and kidney failure (both hard, had to call in a doctor to help them go) and one of congestive heart failure (who went on his own, peacefully) — and I suppose I'm wondering which end of the spectrum we may be heading toward. At this point we are just seeing her get weaker, of course, but don't know what form this takes as it gets farther down the road...

And, of course, if anyone knows of any other supportive herbs or such that might help (with research behind them that I haven't found yet), that would be most appreciated as well!

Thanks so much for being here, and for the opportunity to talk about our little girl...

[DoxieMama]

Welcome back! I'm sorry I don't have any answers to your questions, and only a moment to post (am at work and just popped in for a minute). Hopefully one of the more experienced members or admins will stop by and provide their insights.

[judymaggie]

Avilee -- absolutely no need to apologize -- it sounds like you have been very occupied with helping Daphne regain her quality of life and it sounds like she is doing well in that regard.

In response to your questions, I wanted to provide you with two links. The first is a description of how you can post pictures:

http://www.k9cushings.com/forum/showthread.php?t=7195

The second is a description of some of the situations that can arise with untreated Cushing's:

http://www.k9cushings.com/forum/showthread.php?t=195&highlight=untreated.

One thought with regard to trying Lysodren. There are situations where vets have prescribed a low dose of Lysodren without going through the loading stage. This may be something to discuss with your vet.

I'm sure others will be along to add their good counsel to your situation. One other thing -- if you would like us to change the title of your thread, we can do that -- just give us an idea of what you would want.

A big hug to Daphne!

[Harley PoMMom]

I am sorry that the Trilostane had such a negative effect on Daphne :( As Judy mentioned, a low dose of Lysodren may help.

Trilostane unmasked kidney disease in my boy, Harley, besides the Cushing's he was diagnosed with pancreatitis too. His vet and I agreed that we would focus on his kidneys and forgo the treatment for the Cushing's. Eventually that elevated cortisol had a detrimental effect on his liver and his heart. :( It was around 2 years after he was diagnosed with Cushing's that my precious boy received his angel wings.

Don't know if this will help, Dr. David Bruyette, who is renown Cushing's expert, has published a 3 part series of articles regarding the cause and control of Cushing's disease. In the 3 part he lists the medications that are being investigated for the treatment of Cushing's, here's a link to that and the other articles which are found in our Helpful Resource Forum: http://www.k9cushings.com/forum/showthread.php?p=189827#post189827

Hugs, Lori

[AvileeG]

Thanks Judy and Lori for getting back with resources so quickly — I know I could have spent some time in the resources pages to find the articles I had previously missed, but it had been so long I wanted to go ahead and post the update.

We actually did discuss with our vet whether it is possible to try Lysodren at a low dose, and she explained why the loading dose is generally necessary (it was a few months ago and I don't remember the details, but I'm sure you know)... At any rate, Daphne had severe Addisonian-type symptoms on only ½ the standard low dose of Trilostane, and the nosebleeds set in after a couple of days at only 1/5... so I'd be pretty spooked to try even a low dose of a more irreversible drug like Lysodren. Yes, it could help; but on the other hand, if she were to have an atypical reaction as she did before, it could conceivably kill her.

I looked at the papers by Dr. Bruyette and in that chart of treatments I was quite intrigued by retinoic acid — it sounded very promising until I tried looking up more about it and found that it is incredibly expensive if even possible to get (and I certainly don't want to go messing around with Vitamin A without knowing what I'm doing!). I will probably try asking the doctor about it, in any case, in case it has become more available in the past few years.

My understanding is that even with the standard treatments, the condition will eventually progress, so the treatments are essentially delaying the inevitable... But I am still haunted, as she gets weaker, by what might have been, if she had been able to tolerate the Trilostane.

I did figure out how to make an album of Daphne's profile pictures (http://www.k9cushings.com/forum/album.php?albumid=1099). They kind of came out in backwards order, though (most recent first) even though I uploaded them in chronological order.

Oh, yeah -- I guess Daphne's thread could just be titled "Daphne"...? Or maybe "Daphne -- dealing with a dog who couldn't tolerate Trilostane"...

thanks so much again,
Avilee

[lulusmom]

Hi Avilee and a very belated welcome to you and Daphne.

I have read every one of your posts three times in an effort to understand Daphne's medical history and aside from what looks like a post stimulated cortisol result prior to starting Vetoryl, I could find little clinical information that answered my many questions. I stepped away from your thread multiple times because I wasn't able to bring anything to the table that would help you make any decisions for Daphne without overwhelming you with a boatload of questions. After reading your posts a fourth time, I've decided to come out of the shadows to ask the more obvious questions when trying to wrap my head around the reasons for complications of concurrent diabetes and cushing's. So here goes.....

You joined here in September, 2015 and in your first post you stated that after having borderline cushing's diagnostics three years earlier, Daphne now had a definitive cushing's diagnosis. At this point, I'm not sure what Daphne's definitive cushing's diagnosis was based on. I do know that Daphne had been diagnosed with diabetes mellitus three years earlier which your vet assumed was a result of uncontrolled cushing's. My first thought about this statement is that it would be highly unlikely that you would have ever achieved control of Daphne's blood sugars and gone three years without serious complications of both diseases remaining uncontrolled. This statement is definitely not something you would hear from a pet owner who had been dealing with diabetes and uncontrolled cushings for three years:


I did know about the K9 diabetes forum, and registered and looked in on it a bit initially; but I haven't had many questions about the diabetes for a while because she has been pretty well-controlled since we got her up to her current insulin dose a couple of years ago. Although diabetes can drive you crazy, with seemingly random fluctuations in BG, we manage to keep her in or near her target range at her afternoon nadir at least most of the time.

Aside from hair loss, what was the driving force that prompted you and your vet, after three years, to pursue the cushing's diagnosis again? Was Daphne displaying more overt symptoms associated with cushing's and if so, which ones? Did routine blood and/or urine test screening that should have been done first, show abnormalities consistent with cushing's at that time? Many abnormalities on blood chemistry overlap between cushing's and diabetes so if Daphne's blood sugars were not well regulated, knowing which disease was contributing to the abnormalities would be extremely difficult. While not certain of all testing that was done, I am assuming that the cushing's diagnosis was finally confirmed based on a post acth stimulated cortisol of 30 ug/dL. Is that correct?

With respect to trilostane dosing, your vet prescribed 5 mg compounded liquid trilostane. Was dosing once a day or twice a day?
Which compounding pharmacy filled the prescription? From the very first dose Daphne had a serious adverse reaction to the drug that landed her in the ER. You mentioned that the ER vet said there was no sign of toxicity. What does that mean? Did an acth stimulation test show pre and post cortisol levels above 1.5 ug/dL? Were electrolytes normal? You continued to dose Daphne with the same compounded prescription, titrating doses downward and she continued to have adverse reactions, all of which ceased once you stopped dosing her. Call me crazy but did any of your veterinary professionals get a clue that it was highly probable that there could have been something in that liquid trilostane, other than the active ingredient, that was causing the problem? After assurances from the er vet that Daphne's horrible reaction to the compounded trilostane was not caused by insufficient cortisol, did your vet ever order a new prescription, preferably name brand Vetoryl to rule out bad fillers or questionable bulk trilostane used by the compounding pharmacy?

You mentioned that Daphne had a garlic smell to her after you started treating her with trilostane. It is well known that fillers in some medications can cause various odors, depending on your sniffer, so if the odor resolved within a relatively short period of time, I think you have your answer. It was probably the drug itself.

I have other questions but I don't want to overload you so much that you miss some of them. However, I do have one last question and two comments. Question: How much does Daphne weigh and how many units per injection of insulin is she receiving now? Comment 1: Daphne looks to be a mix of Chinese Crested and Yorkie. The Chinese Crested in her makes her coat follically challenged to begin with but if she's mixed with a Yorkie, that could be double whammy. Yorkies are high on the list of breeds who are genetically predisposed to Color Dilution Alopecia, so this could be a differential diagnosis. You already have the treatment for that condition....a sweater. :) We've seen a few cases of that over the years in blue coated dogs. Comment 2: I looked at Daphne's pictures and besides the hair loss, I would have expected more noticeable changes in the body of a dog who has had untreated cushing's for over three years. I personally don't see that but others may and I welcome their comments.

Based on the information available to me right now, I'm not convinced that Daphne has cushing's and if she does, I'm certainly not convinced she's intolerant of trilostane base on adverse reactions to one compounded prescription, which in my opinion is the likely suspect. Your answers can help me and others try to put all the pieces of Daphne's puzzle together.

Glynda

[AvileeG]

Hi Glynda,
I just want you to know that I am a slow and painstaking writer (a bit OCD about it), so if I don't reply right away, I am not ignoring you! Thank you for your thoughtful questions, I will reply as soon as I get it written...

[AvileeG]

Hi Glynda, I did not forget about your questions — it's been four years' worth of history, tests, and bloodwork (not all of which I have in front of me at the moment), so this will be a long one (forgive me for writing a book here!) and still be somewhat incomplete, but I'll do my best so here goes...

Back in the spring of 2012, what we first noticed was the polydipsia/polyuria (along with an insatiable appetite, but that's just Daphne — when we first adopted her we used to joke that she was the smallest lab on the planet). That, combined with her thinning hair (at that time just a bit), her obvious pot belly, and especially her rising liver values (AlkPhos went from 48 in 2010 to 416 in 2011 to 890 in April 2012; ALT from 54 to 48 to 81) spurred us to ask about testing her for Cushing's. She ahd both the ACTH stim test and an ulrasound, both of which were inconclusive / borderline (I don't have the numbers for the ACTH test at home, but I do know it was out of normal range but not enough to think about treating for Cushing's; the ultrasound showed symmetrically enlarged adrenals but not enough to conclusively show Cushing's). So our longtime, most excellent and experienced Western/TCM vet at the time told us to opt for watchful waiting, and in the meantime put her on Si Miao San, which she said she had seen many mild/borderline Cushingoid dogs do very well on for a long time.

We brought her back in the summer for blood work, which showed her liver values still rising (AlkPhos 1471, ALT 140), along with her blood glucose (152 - borderline / pre-diabetic). During that summer I also tried to quantify her polydipsia — basically counted her tongue-laps per drink (by 8‘s) for a whole day, for a couple of days, and came up with 700-800 day, which I determined to be anywhere from 2-4 times the amount indicating polydipsia (4 oz / 2.2 lbs, in my doggie health book).

By January of 2013, she was eating like crazy but steadily losing weight (down to 10.6 lbs, from 11.8 in the summer), so we brought her in again for more testing: her liver values were up again (AlkPhos 1650, ALT 146), and her BG was up to 281 — enough to start treating for diabetes. At that time, we also did an LDDS test, which showed her just barely out of normal range (1.5 at the 8-hour mark). Our doctor said that diabetes is often a complication of excess cortisol, so it was assumed that Daphne was very mildly Cushingoid which would set her up for the diabetes.

So we started her on insulin (a long process, working her up to the correct dose) — fortunately our doctor was a bit of an expert on diabetic dogs (we sorely miss her right now!), and helped us through the transition. She started at ½ unit of NPH Humulin insulin BID; by July (2013) she was up to 7 ½ units BID, which is where she stayed for two years. She quickly gained back a lot of the weight she had lost (back up to 11.5 by April), her liver values went back down (AlkPhos to 823 in March 2013, 517 the next January, ALT 144 & 112), and her polydipsia also decreased — though her drinking still seemed more than normal, when I counted her drinks again that summer she was averaging more like 400-500 laps / day — about 5/8 of what she had been drinking the summer before. It was quite a relief to have a condition that we could actually treat successfully (even if the threat of Cushing's eventually progressing was lurking in the background).

Through this period (early 2013 - summer 2015) Daphne's hair continued to thin, but very gradually. Since she seemed to be doing well otherwise, I started hoping that maybe the thinning hair didn’t mean much — at one point, we met a middle-aged Chinese Crested at the dog park and, seeing the same basic face shape and odd-looking skin as Daphne, started looking into the breed... and came across a Crested breeder online who mentioned that “hairy hairless” Cresteds “tend to thin out as they age”... Voila! I managed to convince myself that we didn’t have to worry about her hair loss, it was just her breed. (By the way, though many people at the park also look at her and think she is part Yorkie, we don’t believe it for a minute — her immediate predecessor was Alfred the nearly-purebred Yorkie and she does not resemble a him or any terrier in any respect, most especially her personality. The more she loses her hair, the more we are able to see the underlying shape of a Crested in her, so we think that’s pretty much it).

Shortly before last summer, one complication in all of this is that we lost our longtime and very trusted doctor (long story, having to do with letting a corporate vet chain take over the business end of her practice, then finding out it was not as hands-off as her colleagues had assured her it would be... due to the non-compete clause, she had to move away to get out from under the corporate thumb).

So last summer (2015) we saw the pretty-good vet (good manner with the dogs, but Western medicine only) who had taken over. She saw the AlkPhos going up again (800); that, coupled with her hair loss and increasing muscle weakness, led her to suggest that it might be time to think about testing Daphne for Cushing’s again. So we did the ACTH stim test as well as an ultrasound; I do not have the ACTH results in front of me, but I know the doctor said it was definitive for Cushing’s this time; and the radiologist’s report stated: “mild hyperechoic hepatomegaly with plump adrenal glands. Given the results of the ACTH stimulation test, this is most consistent with steroid hepatopathy and adrenomegaly due to pituitary dependent hyperadrenocorticism.” So that is what led us to trying the Trilostane, which you have read about.

As far as contamination of the compounded medication — we were working with a trusted pharmacy which had compounded many medications for us for years; and again, two lab reports from two offices showed no signs of toxicity (which we specifically asked about)... I do not understand how a contaminant could have caused the problem if there was not toxicity involved — if a contaminant leads to such serious side effects, what is that if [I]not toxicity?

The primary symptoms we are seeing now (aside from the hair loss, which is obvious in the photos) are continuing muscle weakness and increased polydipsia (her liver values are staying relatively stable). She is definitely taking much longer drinks (twice as many tongue-laps) than she ever did before, even that first summer, and she is certainly not taking fewer drinks. As for her muscle weakness — since this winter it has been harder and harder for her to climb upstairs (she hasn’t been able to jump on the couch or the bed for a very long time), to the point that she can’t really go upstairs at all any more, even with a “spotter” pushing her from the back. The change in her musculature is not something that shows up in the photos so much (since her shoulders and hips used to be covered by hair), but it has has been fairly dramatic — she really has almost no muscles left on her arms and legs. This spring she was trudging so slowly on all her walks we were beginning to think she was going downhill fast... but she did perk up considerably when we started food rewards for walks, so we have been somewhat encouraged in that regard.

I would very much like to think that all of this is caused by something other than Cushing’s, with an easier treatment profile... I know the symptoms of Cushing’s are often mistaken for old age, and I would like to think perhaps we have simply mistaken old age for Cushing’s — except that she is only 13 (perhaps it’s unfair to compare her to Alfred the Yorkie, but he was in perfect health until his kidneys gave out at nearly 18), and her muscle wasting has been so severe.

All that said — we now have another wonderful Western/holistic/TCM vet (recommended by our previous longtime doctor) who is able to advise us on supportive herbs and nutrition... And again, Daphne is a contented little girl who still has a good life as long as she has her people and good food.

Sorry this is so long, this is the only way I know how to answer all those questions fairly coherently — thank you for reading this far!

Avilee

[AvileeG]

Hi again,
After I finished that long monograph on Daphne's history and posted it late last night, I started remembering (of course) the things I left out... One thing that jumped out at me from your questions was the part about it being highly unlikely we could ever have achieved control of her blood sugar for as long as we did if Cushing's were truly a factor. A few things occurred to me:

1. Daphne is and has been on a fairly large dose of insulin to keep her regulated — 7 ½ units of NPH for a 10 - 11 pound dog. This does not put her in the range which defines insulin resistance (2U / kg or approximately 1U / lb), but it does put her fairly high in the "non-resistant" range. This was naturally a source of frustration during the half-year it took us to gradually creep up to the dose that finally got her under control...

2. Daphne's life is extremely consistent and well-regulated in order to keep her blood sugar under control — homemade hypoglycemic diet, thoroughly measured, meals nearly exactly 12 hours apart, any treats exactly the same every day and accounted for, and multiple walks to help the insulin work, at the same time every day, most importantly right after meals / insulin injections (this is something we learned from our neighbor, himself a type-1 diabetic and diabetes geek) — we do everything we can to keep her routine consistent so as not to throw off her blood sugar. Even at that, she has huge and frustrating swings, which we understand is often just the part of diabetes that can drive you crazy... By "well-regulated" I simply meant that she made it into her target range at the afternoon nadir more often than not. Even that has gone by the wayside since the events of last fall...

3. Our longtime vet was a very experienced TCM (Traditional Chinese Medicine) specialist as well as allopathic practitioner. If she had experienced Si Miao San holding off further symptoms in borderline Cushing's dogs, I have no doubt that that medication may have helped to keep Daphne's symptoms at bay for a couple of years. Traditional and herbal medicines can be quite powerful — which is why I would never use them without the guidance of an experienced doctor. (This is the main reason we changed doctors last fall, as the allopathic doctor who moved to the head of the practice after our longtime vet moved away was not able to advise us on how the TCM herbs Daphne was already taking would interact with any new Cushing's medications.)

Sorry, this got pretty long again — thank you so much for your help and concern...

[lulusmom]

Thank you for your response. I sincerely appreciate the time you took to present all of the helpful information. Even with all that beautiful information, I still have a few questions and comments. :o

The words toxicity and overdose as it relates to trilostane are interchangable so when the er vet told you that there was no evidence of toxicity, I believe s/he was referring to an overdose that was ruled out by the results of either acth stimulation test or possibly a baseline cortisol that showed no evidence of cortisol insufficiency caused by too much of the drug. You mentioned that they said toxicity was ruled out after two lab tests were done. Can you please get copies of those tests and share the results with us?

Unless the er vet shipped Daphne's bottle of liquid trilostane to a qualified lab for examination, there is no way the er vet could have determined if a bulk drug or any other filler in a compounded med is contaminated nor could they have confirmed that the dose in the capsule matched the dose stated on the bottle. Once your vet knew that the er vet ruled out overdose, did your vet order a new prescription of trilostane or did you continue to use the same bottle for the multiple reduced doses that continued to make Daphne sick? We have a number of trusted compounding pharmacies members use and recommend. Which pharmacy compounded Daphne's trilostane?

With respect to insulin requirements, I am certainly not well versed on the finer points of DM but I've followed enough threads of dogs with both diseases and have seen a number of those dogs misdiagnosed with cushing's. I still question a cushing's diagnosis in a dog who has been suspected to have had uncontrolled cushing's for over three years yet whose bg is fairly well regulated, though on a higher dose of insulin, and is not displaying more overt symptoms that cannot be explained away by breeding, diabetes and even old age. Has your vet ruled out degenerative disk or joint disease as a reason for or a contributing factor in muscle wasting and weakness?

I realize that Daphne has been receiving Chinese herb treatment but unfortunately, there is no science based evidence that Chinese herbs or any other alternative treatment effectively reduces cortisol. I am very much a science based person with an open mind and anecdotal evidence is great if you are dealing with a benign problem but cushing's is not benign. Did your vet perform any acth stimulation tests to determine if the Si Miao San was having any effect on the cortisol or was her primary objective to alleviate symptoms?

So now we know that the hair loss could very well be Daphne's breeding but you said that Daphne's drinking is enough to meet the criteria for polydipsia. Dogs with cushing's have polydipsia because they have polyuria, meaning they drink tons of water because their kidneys have lost the ability to concentrate the urine and they are peeing huge volumes of dilute, odorless urine. If they don't drink enough to keep up with the loss of fluid, they can dehydrate quickly and even die if water is withheld. Is Daphne peeing huge volumes of urine and having accidents in the house? Has your vet done a recent urinalysis, with culture, to check urine specific gravity as well as rule out a UTI?

Sorry for so many questions but Daphne is certainly not a textbook case.

Glynda

[AvileeG]

Hi Glynda,

I think the perhaps timeline in my early posts has been a bit confusing here -- we did not see the emergency vet until the very end of the trilostane episode (actually a day after we had stopped it entirely). So no one had ruled out overdose between the (brief) trials of trilostane. To clarify -- after two doses at 1mg/kg, Daphne presented symptoms which appeared to be possible overdose. The doctor did not put her through another ACTH stim test after only two doses, but advised us to wait a few days and then try again at half that dose. She again had a severe reaction after one dose at 0.5mg/kg, so again we stopped and waited a week before trying again at 1/20 the original dose (0.05mg/kg), gradually increasing to 0.2mg/kg. The nosebleeds began her 2nd day at that dose, on a Thursday -- she finally ended up at the emergency clinic Friday evening, after our regular vet clinic failed to call us back in time to bring her in (one reason we are no longer with that clinic). At no time in this process did our vet suggest that we should do another ACTH stim test, and we did not question that since our understanding from all we had read was that monitoring is usually done a week or two in. We do not know how experienced this doctor is with Cushing's, and we are no longer taking Daphne to that clinic (again, this was the vet who was the junior doctor in our longtime vet's practice, and who took over after our own vet had to move away).

In regard to the question of "toxicity" vs. "overdose": by the time we went to the emergency clinic, we had already read multiple suggestions on this thread that the nosebleeds could be related to arsenic poisoning, among other things, so we specifically asked about any indications of toxicity in relation to that. The emergency vet was very clear that there was no indication of any sort of poisoning, since her WBC and RBC counts were normal. He did NOT tell us that there was no trilostane overdose.

So where we are at this point is that we have no definitive proof that it was the trilostane itself that caused her extreme reactions, since there were no further ACTH tests done at the time; but we do have the opinions of two doctors, based on two sets of bloodwork, that there was no poisoning.

As far as whether she actually has Cushing's, the ACTH stim test and the ultrasound done in August both showed Cushing's (no, I do not have the ACTH numbers in front of me, but apparently they were enough to convince the radiologist).

We have seen no signs of degenerative disc or joint problems. She did have an x-ray earlier this year (January, I think). At any rate her exercise routine has stayed consistent, so it would be unlikely for muscle atrophy to occur so rapidly simply due to lack of exercise (the only way joint problems would lead to loss of muscle mass in the first place). Her muscle atrophy, again, has been dramatic over the past year -- her adductor weakness makes it difficult for her to stand on non-carpeted floors, and her spine, shoulder- and hip-bones are now prominent due to lack of surrounding musculature... It does not show up as well in the pictures, but please believe that I know this dog very well and her muscular weakness is not just "old age."

You say that "now we know that the hair loss could very well be Daphne's breeding" -- actually, I do not see that. The color dilution alopecia theory looks rather unlikely, as that begins early in life (even if she were part Yorkie). As far as hairy hairless Cresteds "thinning out" as they get older: I was happy to jump on that for a few months to convince myself I didn't really have to worry about Cushing's, but that is the word of one breeder -- for all I know, this breeder may have a bunch of inbred purebreds which are predisposed to Cushing's or something else, and this is his rationalization...

Yes, I do know how polydipsia and polyuria work, and yes Daphne does pee large volumes. She does not pee in the house because she gets many many walks. She did not have a UTI when she saw the doctor in late April, her specific gravity was high as it always is; urinary issues are something that we always check on, of course.

As far as the Chinese herbs: I am also science-based (that is why we opted to try Cushaway, because melatonin and phosphhatidylserine are among the few alternatives which do show some promise for reducing cortisol in the peer-reviewed research literature). However, I do know that there are traditional remedies which do not have as extensive a profile of peer-reviewed research (for various reasons, some having to do with how research gets funded), but which still have powerful effects (as was borne out in cautions from an old friend who is a research-physician at Johns Hopkins -- as he said, herbs can be powerful medicine that you don't fool around with without knowing what you are doing!). No, I do not expect that that Daphne's herbs effectively reduce cortisol in the way that the standard medications do -- they are supportive; and in the absence of a standard medication that we are confident she can tolerate without life-threatening effects, supportive therapies are what we are working with at this point.

Sorry for going on at such length again — and sorry if I might seem to be getting a tiny bit cranky... I do appreciate your concern, I guess it just feels like I'm being questioned on the diagnosis of Cushing's while simultaneously being challenged on our decision not to retry the standard Cushing's medications... I do know that Cushing's is not benign, and I do wish there were something we could do without the potential of sending her into another tailspin; and again, I would be delighted if her symptoms were all due not to Cushing's but to something more easily treatable (for her)... I know that Daphne is not a textbook case -- all of this would be a lot easier if she were!

thanks so much again,
Avilee

[lulusmom]

I am certainly not challenging you on anything, I am simply asking questions about things that don't make sense and bringing information to the table that perhaps you had not thought of. What I don't want to happen is for you to leave and not receive the support you came for so I am going to step away from your thread and allow others to help you. Since I have hijacked the conversation and most likely moved the focus of your thread in a direction you didn't want to go in, I hope you will restate any concerns you may have and ask any questions that may not have been answered. There are a lot of educated and experienced minds here and they will not let you make this journey alone.

Before I leave I would like to share one more thought. Over the years I've seen many dogs with diabetes and cushing's present with complications that have, more often than not, been well above the average gp vet's depth of knowledge and experience to resolve long term. That's not to say that your vet isn't awesome. I'm just saying that even with the best gp vet I have ever had the pleasure of working with, if my own dog had both diseases, I would be asking for a referral to an internal medicine specialist. I routinely recommend that to any members who are dealing with both diseases and I hope that might be something you would consider for Daphne. No matter what, I sincerely hope you can get your girl stabilized and on her way to a better quality of life.

Glynda

P.S. If Daphne's USG is high, she would not have polyuria as that would be an indication that her urine is overly concentrated and would not be the likely cause for her excessive water intake. Dogs with cushing's have low USG. I think that was probably just an oversight on your part. Heaven knows there are a lot of things to remember.

[AvileeG]

Hi Glynda,

I'm sorry if I got sounding snippy and I certainly didn't want to chase you away! I do appreciate your concern, I think I was tired and possibly overwhelmed with many questions, many of which can't be answered adequately (because of the lack of definitive proof of trilostane overdose)...

I think the suggestion of an internal medicine specialist is could be a good idea (I'll admit we were put off the idea when we were at our former vet clinic during this crisis, and a specialist was called in who tried to advise us without ever having actually looked at Daphne herself!) -- I will check with our vet for recommendations to a good one.

In any case, Daphne has been pretty much stabilized of late -- her major decline occurred last fall-winter, after the trilostane trial, and she had held pretty steady since then; although we are still seeing some further decline in muscle mass, is has been not nearly as precipitous. As long as she gets plenty of good stuff to eat and an abundance of mommy-lap time (which is in good supply during summer break), she is quite the happy little girl.

thanks,
Avilee

p.s. You are right, I did mess up on the USG -- I was thinking of high volume and typed that word by accident...

[molly muffin]

How has Daphne's electrolytes been through all of this?
We have seen dogs who cortisol shows within normal standards when on trilostane, but have a what I can only call an electrolyte reaction, where those end up going too high or too low and this is what can cause a very severe life threatening situation even.
I haven't seen it all that often, but we do have a current member whose dog has to take even lower doses of trilostane than one would expect because of that very issue. I'm not sure if they checked the electrolytes or not, or would even think to after 2 doses, but it's certainly a though and what popped into my head.

[AvileeG]

I don't know anything specific about her electrolytes at the time of the crisis last fall, but she did have two complete sets of standard bloodwork at the time (one at the regular vet clinic, one at the emergency clinic), and apparently nothing about her electrolytes popped out at anyone then. Since then she has had multiple visits with our new doctor, with her last bloodwork in April; I did ask about potassium specifically because of her polyuria (since in our previous experience with CHF and kidney failure patients we have had to give potassium supplements because of losing it in their pee), and her electrolytes as of April are normal.

[molly muffin]

Hmm, then it wasn't an electrolyte issue as that would have shown up on the blood tests. Potassium, sodium, etc being normal.

[AvileeG]

Yes... Nothing other than the Cushing's- and diabetes-related symptoms (high liver values and blood glucose) has ever shown up in her bloodwork, so that's pretty much what we're left with.

I've emailed the doctor to see about getting the actual numbers from her ACTH stim test last summer -- after some of Glynda's questions, I'm wondering if Daphne's earlier "incipient" Cushing's was so very slow-growing that by last summer she was just barely over the line, with such low-grade Cushing's that trilostane wasn't really warranted after all... We have seen a decline in her health since then, but nearly all of it was last fall after the trilostane trial -- ironically, whatever idiosyncratic reaction she had to that medication seemed to kick all her visible symptoms into high gear! Since January she has continued to lose hair and muscle mass, but much more slowly, so we are kicking ourselves wondering how much better off she would have been if we hadn't tried the trilostane at all.

[AvileeG]

Okay -- I got the copy of last August's ACTH stim test from the doctor yesterday, here are the numbers:

pre-ACTH: 5.1µg/dL (ref: 1.0 - 5.0)
post-ACTH: 30.5 µg/dL (ref: 8.0 - 17.0)

So, it looks pretty definitive, given that high post-ACTH reading...

I guess my question, looking at this, would be how much does the pre-ACTH cortisol concentration tell us? Since Daphne's was just barely out of reference range, could that mean that her constant dose of cortisol from her disease isn't as severe as it could be (I'm probably indulging in a bit of wishful thinking here)? Or is the pre-ACTH level pretty much stochastic, reflecting more about how much stress she's going through at the time (not a whole lot, for this one at the doctor's office)? I know it is the post-ACTH number that is used for diagnosis, so I suspect that the latter is the case...

[labblab]

Unfortunately, it's the latter. Baseline cortisol readings are variable even within the course of a normal day, and there can be a lot of overlap of readings among dogs who do and do not have Cushing's. That's why baseline cortisol alone can never be used to diagnose the disease.

Marianne

[AvileeG]

Yeah, that's kind of what I figured -- thanks for confirming...

[AvileeG]

I guess I haven't posted here in a while, been too busy dealing with keeping Daphne comfortable and happy, among other things...

... So, our little princess has left us — it's two weeks ago now, I suppose it's taken me this long to be able to write about it. She continued to get weaker through the fall and winter (as of last summer and even into the fall, she could still run a little bit on her walks, with Cheerios for an incentive). Sometime in the fall, she really couldn't run anymore, and her walks got slower and slower. We started walking her with little booties because she wasn't picking up her feet and was scraping her toenails too short; but even that stopped working as she scraped holes in her booties and and came back from one walk with a bloody toenail.

So around about Thanksgiving, we started just walking her in the house — she would do "laps" up and down the hall (for treats, of course); plus her best game was "magic carpet," where we would put Cheerios all over the living room carpet for her to find (being nearly blind, it could take her a while, and she got some exercise in the process). As the weather got worse, this was a more attractive option anyhow — she never was very happy about going out in the rain, and she never much cared for socializing with other dogs (except for the few she knew well as neighbors), so being an inside dog was perfectly fine with Daphne.

Through it all, she was quite content. Eating got to be literally more difficult for her, as her tongue and facial muscles were atrophying it got to be harder just to pick up the food, so we made it into little gelatin squares which were easier for her to deal with, and she still looked forward to her meals. Right up to the end, she was wildly enthusiastic about her bedtime treat of duck jello (our answer to the question of what to give her that wouldn't spike her blood sugar), as well as the ubiquitous Cheerios that were her incentive to move around... and she was also very happy sitting in my lap, or snuggling with her daddy.

Two weeks ago she seemed to have some kind of crisis, as she woke Monday morning with her heart and respirations faster than her usual. This continued intermittently throughout the day and seemed to grow worse in the evening, to the point that we were considering calling the house-call doctor if it continued the next day. She still enjoyed her dinner and looked forward to her bedtime duck jello as usual, then rested quietly, snuggling on the couch, until about 3:00 am when she got restless, needing to go out to pee... So Daniel took her across the street to her favorite lawn, and as he was carrying her back home he felt her head slump — and back at home he got out the stethoscope to listen for her heart, and she was gone. She died in her daddy's arms...

We are grateful that she was comfortable and happy right up to the end, and that she went in her own time... We have had dogs with painful diseases, for whom we had to make the decision to euthanize so they wouldn't suffer any longer; but Daphne did not have a painful disease, only one that made her very tired, and had no suffering that we could see. Even though her world had shrunk, she still enjoyed life right up to her last day. She has left a big hole in our lives, but we are glad that even her last days were good ones...

[AvileeG]

p.s. - I've posted Daphne's obituary page in her albums
(http://www.k9cushings.com/forum/album.php?albumid=1160) - including pictures of her back when she still had hair...

[labblab]

Oh my, I am so deeply sorry for the loss of your dear little girl. Thank you so much for returning to tell us what has happened, though. Daphne now joins our other angels on our special memorial thread of honor:

http://www.k9cushings.com/forum/showthread.php?t=8383

I've just now visited your obituary page, and it is so lovely. I'll be contacting you soon to see whether you'd also like for us to add a photo link to Daphne's line on our "Remembering" thread. In the meantime, please know our hearts are with you.

Always in loving memory of sweet little Daphne ~ Always in honor of a life so very well-lived.
Marianne

[Harley PoMMom]

I am so sorry for the loss of your precious girl, Daphne, and my heart goes out to you and your husband. Please know we are here for you and always will be.

With Heartfelt Sympathy, Lori

[Joan2517]

I'm so sorry, too...she went peacefully and in her Daddy's arms, I hope that brings you some comfort. I'm sure that Daphne felt surrounded in his love as she passed.

[DoxieMama]

I'm so sorry to hear of the loss of your sweet Daphne.

[Squirt's Mom]

I am sorry to hear about your sweet girl. Fly free, precious one, fly free. Thank you for coming back to let us know...that had to be difficult for you. Know we are here anytime you need to talk - we DO understand that bond more than most.

Our deepest sympathies,
Leslie, Trinket, Sophie, Fox, Bud, and all our angels at The Bridge


Remember Our Love

I was chosen today
I'm learning to fly
the world took me away,
but please don't you cry

And I chose you today
to try and be strong
so please don't you cry
and don't say that I'm gone

When you're feeling alone
just remember our love,
I'm up near the stars
looking down from above.

Remember our love
In a moment you'll see
that I'm still here beside you
when you're thinking of me.

Julie Epp

[LaurieS]

I'm so sorry for your loss of your precious girl. But I wish all of our babies could have an ending that peaceful so I hope you have comfort in that. My heart still aches for your loss and I have tears as I type this because I so understand what you went through.

Laurie (and Charlotte who is still fighting the good fight)

[rainiebo]

What an awesomely beautiful ending for a much loved pup. Thank you so much for sharing how she left in her daddy's arms, she made it to the end just as she had lived her life, in the care of her sweet doggy parents.

[molly muffin]

I am very sorry to hear of the loss of your beloved Daphne.
I am inspired by the jello cubes of duck and favorite foods. What an inspiration you are for other dog parents. I never thought of that one. :)

Daphne was a lucky little girl. I like the cheerio idea in the living room for exercise too.

A life well lived. That is a good expression and what we all wish for our furbabies.

[AvileeG]

Thank you everyone for your kind thoughts... Daphne has certainly left a big empty space in our home and our lives, but I am going back to memories of her early days — as well as remembering what a trouper she was in her last years. Had I known it was her last night, I would have given her more of a backrub and snuggle before going to sleep that night... But she did enjoy her duck jello bedtime treat, only a few hours before she died, so her passing was about as peaceful as we could have wished.

Thank you again... I wish I had been more active here over these years (school takes up so much of my time) — those of you who are able to post more frequently and have so much good advice for us all are invaluable.