Angelina 13.5 year old/13kg Maltese Cross on Trilostane

[Lulusmom]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,

Regarding information on twice daily dosing, check out page two of the monitoring flowchart for dogs whose clinical signs are not controlled for a full day. It say to slowly increase the dose and divide twice a day. In other words, if a dog is getting 60mg a day, you would increase to something like 80mg divided which would be 40mg twice daily. This is also recommended by UC Davis. This information is not really clear in the article included in the Vetoryl/Trilostane information posted by Marianne, I did verify the UC Davis protocol on twice daily dosing via an audio of one of Dr. Edward Feldman's lectures. He used that exact example I mentioned above.

If a post stim number is within the desired range of 1 - 5 but the dog is still showing overt symptoms, this is a pretty good indication that twice daily dosing should be prescribed. Angelina's post stim was definitely well beyond the desired range. The correct way to determine if a dog needs twice daily dosing is to do a urine cortisol creatinine ratio which requires that the pet owner bring in a urine sample collected the morning before the acth and before meds and meal. If the ratio is abnormal, that is a good indication that the once daily dose is not lasting through the night. It looks like your vet made the call to switch to twice daily dosing based solely on unresolved symptoms that could be explained by the high post stim number as opposed to proof that the current once daily dose was not adequately controlling the cortisol overnight. However, I do recall that you mentioned that Angelina's symptoms seem to get worse at night which your felt was a good indication that twice daily dosing may be necessary.

http://www.dechra-us.com/File/vetory..._Flowchart.pdf

Every dog responds differently and it could be that Angelina will do just fine on a 100% increase in dose; however, I personally don't think that a post stim number 13 ug/dl after only two weeks of treatment is high enough to make me feel comfortable with that kind of an increase. Just be ever vigilant in watching for signs that cortisol may be too low.

I'm not sure about that Trilostane affects a dog's taste in food. It sure had no effect on either one of my chow hound's taste buds. Their appetite did decrease by they never turned their nose up to food. This is definitely a sign that cortisol can be too low and you should never give Trilostane to a dog that is not eating normally. If either one of mine looked the slightest bit off and wasn't doing their normal head dive into the bowl, they were off Trilo for a few days or until they were back to normal. Try eliminating the fish oil on a meal and see if that makes a difference. If not then you can rule that out as a factor which would make Trilostane the bigger suspect.

I am about as far from a medical professional as you can get but I still respectfully disagree with your vets and don't think that Angelina's numbers were that high after only 15 days of dosing. All dogs respond differently to Trilostane so the fact that another Maltese has done well on the same dosing regimen is irrelevant. A perfect example is my two cushdogs. My 4.5 lb Pom was on 30mg once daily for two years and my then 10 lb Pom was on 15mg twice daily and both were effectively controlled.

You know Angelina best so if you think something is not right, and a cushdog that doesn't eat normally is not right, then don't continue to dose her.

Hope this helps.

Glynda aka The Oracle

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Glynda to the rescue!

So, going by the flowchart you basically stick to the initial dose for a full month, unless there are signs of:
1) Post-ACTH serum cortisol <1.45 μg/dL (<40 nmol/L) and clinically well
2) Corticosteroid withdrawal syndrome
3) Hypoadrenocorticism
(If its points 2 or 3 you discontinue the dose and have an ACTH stim test done to determine the problem).

However if:

Post-ACTH serum cortisol >1.45 μg/dL (>40 nmol/L) and clinically well*

But wait! I see an asterisk on the flowchart - which leads to:

* If the post-ACTH cortisol is >9.1 μg/dL (>250 nmol/L) and the clinical
signs of HAC are marked then you should consider a dose increase
at this stage. Increase dose by smallest increment possible.

So an increase after day 14 is advised? Since this is Dechra's chart the "smallest increment possible" they would be talking about would be 30mg? That's the smallest they are making now (from memory). If that's the case, unless I'm completely confused, then a 30mg to 60mg jump is what they are advising?

Note all the question marks?

So the problem at this point is not the increase in dose, but the splitting the dose in two? Which should only happen after day 30? Which leads to:

[QUOTE=Lulusmom] In other words, if a dog is getting 60mg a day, you would increase to something like 80mg divided which would be 40mg twice daily. [QUOTE=Lulusmom]

So, eventually the dose is likely to be bigger?

And as far as determining twice daily dosing:

[QUOTE=Lulusmom] The correct way to determine if a dog needs twice daily dosing is to do a urine cortisol creatinine ratio which requires that the pet owner bring in a urine sample collected the morning before the acth and before meds and meal. If the ratio is abnormal, that is a good indication that the once daily dose is not lasting through the night.[QUOTE=Lulusmom]

[QUOTE=Lulusmom] Just be ever vigilant in watching for signs that cortisol may be too low. [QUOTE=Lulusmom]

This morning after breakfast - and her morning dose - I took Angelina out for a short walk. The way she was walking was painful to watch. But I couldn't be sure if it was signs of "Corticosteroid withdrawal syndrome (“relative” cortisol deficiency characterized by weakness, stiff gait)" or Hypoadrenocorticism (e.g.weakness) - I hate the way the symptoms overlap! So. should I discontinue for a few days or rush Angelina off for another ACTH stim test? Or just cut back to the 30mg per day?

Last night's dinner was fish oil free and although Angelina paused to consider it - she did finish every bit of it.

Thanks Glynda for such a thorough response!

John II

[Lulusmom]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,

Here in the US, a lot of vets (including UC Davis) use compounded versions of Trilostane when needing to adjustment a dose that isn't available from Dechra. Lulu was too small for the 30mg available from Dechra so we had no choice but to have her 20mg compounded. We ultimately increased to 30mg which is where she stayed until we switched to Lysodren almost two years later.

I'm glad that you took the time to check out the Dechra flowchart. The chart is meant to be a general guide but as my vet explained to me, you have to look at the big picture. She had never treated with Trilostane but after researching, she decided that it was best to have an acth stim test before starting treatment so that she would have a baseline to compare to the 14 day post stim test. This told her how quickly and how much the cortisol had dropped in a two week period. I hadn't found the cushings forum yet so I hadn't witnessed all the disparities from dog to dog when monitoring treatment so I was very grateful that she was so thorough. Jojo's cortisol continued to drop after the 2 week stim so had she increased his dose right away, his cortisol would undoubtedly have dropped too low. She did a great job considering Jojo was her first Trilostane patient.

Trilostane has a short half life and its enzyme blocking abilities start to diminish after 8 to 12 hours. This is why some dogs will eventually require twice daily dosing if symptoms don't resolve on a single dose. Since every dog is different, you don't know at which hour the Trilostane begins to wane so when you go to twice daily dosing, there are hour(s) in the day that there can be an overlap in dosing. This is why it is recommend that you up the dose a bit and split in two. Like I mentioned before, if a dog was at 30mg once daily, you'd up that to maybe 40mg and split it into 20mg twice daily. In essence you could have an overlap of a total of 40mg. If you simply double the dose like your vet did, a possible overlap would be 60mg. That's a big difference in my opinion.

Jojo was a mess when he first came to us and not only was he extremely weak in the hindquarters, he walked with an incredibly stiff gait. This is a rare symptom of cushing's called pseudomyotonia and sometimes it resolves once the cushing's is controlled and sometimes it doesn't. Jojo still walks like he is on pegged legs but his IM doesn't seem to think it has progressed or will be a problem for him in the future.

I hope all this makes sense but if not, Marianne is excellent in explaining much better than I can and hopefully she can clear the fog I've created in your head. I trip over my own words sometimes, become too verbose, lose my place, need access to spellcheck and eventually put people to sleep or maybe just into a catatonic state.

Glynda

[Roxee'sDad]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,
Glad to see you back. Can't help much with the once or twice a day dosing. I'm still trying to figure out what the best route is for Roxee. Thinking about a UTK panel but will make that decision within the next few weeks.

Regarding her apetite....When the trilo kicked in, Roxee got very, very picky about what she will eat. It has to smell good otherwise she would and still does walk away. Worried me at first but this was a good sign that the trilo was having a positve effect. I have her to 4 meals a day now trying to keep the weight on her. The more and more I read, this (weight loss) seems to be an unspoken side effect of trilo. Oh BTW - her potbelly is completely gone now.

Jojo was a mess when he first came to us and not only was he extremely weak in the hindquarters, he walked with an incredibly stiff gait. This is a rare symptom of cushing's called pseudomyotonia and sometimes it resolves once the cushing's is controlled and sometimes it doesn't. Jojo still walks like he is on pegged legs but his IM doesn't seem to think it has progressed or will be a problem for him in the future.

Glynda just gave me some homework, (pseudomyotonia) this is exactly Roxee's symptoms. Since starting treatment, it has improved somewhat. She doesn't hardly fall over anymore so hoping it continues to improve.

Well, keep up the good work with Angelina and keep us posted.

All the best to you and yours including a belly rub for Angelina (if she'll let you)
John (Roxee's Dad)

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hello All,

Even before I read the 2 new posts, I just want to submit my apologies all round for my earlier post because I should not be trying to think this through on 3 hours sleep!

John II

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

And now to continue...

I think that if Glynda is "The Oracle" then John must be "The Guardian"

This is tricky stuff and I wish I could find one of these "think outside the formula" vets that some of you have been lucky enough to find. Anyone know of one in Sydney?

Anyway - just a update about today. It's cool and windy here - which helps Angelina. Back on a single 30mg dose of trilostane. As the afternoon wore on, the trilostane wore off and the cortisol kicked in, she was walking straighter - still not great, but improved.

Angelina insisted on dinner at 4:30pm. Same stuff as yesterday - and the day before - but she didn't hesitate. And shaved about 15 seconds off yesterday's time.

After which she went for an afternoon stroll down the street and back. Less of an old lady dog than this morning.

From Roxee'sDad:
"When the trilo kicked in, Roxee got very, very picky about what she will eat. It has to smell good otherwise she would and still does walk away."

I knew I read that somewhere!

And I'm wondering if there's an Australian version of a UTK panel?

Actually Glynda, here in Australia we're in the same boat - our Trilostane is compounded too. Although I did find (on my wanderings this morning) a submission to the government to import Vetoryl into Australia dated just last February:

http://www.apvma.gov.au/gazette/0902...ds/page_16.pdf

"The Australian Pesticides and Veterinary Medicines Authority (APVMA) has before it applications from Dermcare-Vet Pty Ltd for approval of the active constituent trilostane and registration of products containing the active constituent trilostane. The products are VETORYL 120 MG CAPSULES, VETORYL 60 MG CAPSULES and VETORYL 30 MG CAPSULES. The products are for use on dogs."

We may be getting access to the name brand soon? Now we just need to convince Dechra to make it in 10mg and 20mg capsules! It also goes on to answer a few of those pesky exposure and environmental questions I had.

And apologies again to Glynda - my earlier sleep deprived brain misunderstood your reference to 60mg and 80mg doses - which I should have realised translated to 30mg SID becomes 20mg BID.

Believe me Glynda, as far as I'm concerned - nobody could be too verbose for my liking. Tell me more, tell me more!

John II

[BestBuddy]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,
I was lucky that I was close to the University of Melbourne and the specialists there, surely Sydney has something similar.
Dermcare-Vet was importing Vetoryl early in 2006 when Buddy was first diagnosed but they ran into problems and stopped being reliable so compounding was the only option. It was still possible to order from the UK for a short time but that loophole was soon closed unless you got through all the red tape and imported it yourself.
Jenny

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi Jenny,

Do you mean you got a UTK-type adrenal panel done in Melbourne? Or that the Melbourne University vets are the kind who actually do the right thing without having to be prompted?

John II

[Lulusmom]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,

The University of Tennessee Knoxville (UTK) is the only facility in the world that does the adrenal panel. They also do the panels for patients all over the world. Shipping must be done properly so the cost to you would be higher but your vet can contact UTK and get instructions on what to do. Just remember that Angelina would have to be off of Trilostane for about a month before doing the panel.

Quite honestly, if I lived in Australia and my dog was not doing well on Trilostane for any reason or I suspected that my dog had elevated sex hormones, I think I would forego the expense of a UTK panel and consider switching treatment to Lysodren. Lysodren is very effective in controlling cortisol as well as the other adrenal steroids/hormones. Estradiol is the only sex hormone that can also be found in other bodily tissues outside of the adrenal gland but Lysodren is only effective in controlling this hormone if it is confined to the adrenal glands. I personally wouldn't be too concerned about that as I don't recall any members treating with Lysodren reporting that despite routine acth stim tests showing post cortisol within range, their dogs symptoms remained unresolved for over six months.

If you are still interested in the UTK panel, here is a link to their website and be sure to share this with your vet:

http://www.vet.utk.edu/diagnostic/en...logy/index.php

If you are using a compounding pharmacy then I am unsure as to why they can't package 20mg capsules. Some pharmacies will also repackage for you so that might be an option if you and your vet decide to lower the twice daily dosing to 20mg. By the way, Dechra manufactures Vetoryl in 10mg, 30mg, 60mg, and 120mg capsules, however, the US has only approved the 30mg and 60mg capsules. I believe they are working on getting the FDA to approve the 10mg and 120mg.

Glynda

[LuvMyMunchie]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,

Although I've been following Angelina's story, this is the first time I've posted to your thread. Basically, I've just stopped by to say, "Hi...how are ya".

I wish I could find one of these "think outside the formula" vets that some of you have been lucky enough to find.

Good luck on your vet quest! I've been searching for 2 years....and I'm still searching for one who doesn't think one dog is an exact clone of all others!!!

Glad to hear Angelina was feeling a bit more chipper for her stroll. That's a good sign.

Take care,
Louise

[BestBuddy]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hi John,
I have nothing but nice things to say about Buddy's treatment and care at Melb Uni and especially the specialist in charge of Buddy. I didn't know anything about the UTK type testing when Buddy was dx so I never asked but my special specialist was silly enough to give me his email address so I am going to ask. I will be back if I can get an answer.
Jenny

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hello All,

Glynda,

Isn't it odd that only one place in the world does the UTK type Adrenal panel? If we weren't all losing our life savings paying medical bills we might otherwise be able to pool our resources and establish a grant to get more specialist hospitals the funds to incorporate this test into their practices. I'll keep that in mind for when I win the lottery.

I'll keep Lysodren on hold as an option - I'm beginning to think I may need a new vet to point me at a new specialist. Time will tell - but after sinking $2000 into this specialist so far (not to mention another $600 to the vet before that) I'm worried about starting over. Especially if you don't know what you're getting. New mantra: lottery lottery lottery lottery lottery lottery. I hate to be thinking about money - but seriously everytime I see a bill it's like the receptionist punched me in the stomach!

I haven't been directly to a compounding pharmacy - the specialist simply handed me a jar of 100 x 30mg capsules of Trilostane. The original label - including handling instructions was obscured by the new printed label for Angelina to take one per day. The only warning on the new label was "Keep Out Of Reach Of Children".

Louise,
Thanks for keeping tabs on Angelina's Tale (Angelina's tail keep curling up - so she doesn't seem too unhappy about things ) and stopping by to say "Hi". As for me - I'm cramming information into my skull, confused, sleep deprived, frustrated, worried, sad, 8 kilos lighter since Christmas (forget the Atkins Diet! The Cush Dog Owners Diet is way more effective! )

Jenny,
Thanks for your help as always!

Thankfully Yours,
John and Angelina.

[BestBuddy]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Well I got a reply about something similar to the UTK panel from the best specialist in the world (in my opinion). It is not available in Australia but he did try to have run what he called the "17 OH progesterone" and was messed around by the pathology company and could not get the results. I guess it will be something hopefully that can and will be done here in Australia but it seems like it will be a long way off.
Jenny

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Well Jenny thanks anyway for checking.

Does it seem to anyone else as though the universe moves in mysterious ways to thwart Cush Pup Parents? Or am I just getting paranoid.
It should be much simpler than this!

John II

[John II]

Re: Angelina 13.5 year old/13kg Maltese Cross on Trilostane

Hello All,

I think my hair turned grey (greyer ) today.

Angelina was lying next to the fridge. Eventually, I wanted access to the fridge. Angelina tried to get up - but couldn't. She started screaming. Not a sound I EVER want to hear again. I helped her to her feet and the screaming continued. She could not use her front, right leg!!!

Had she somehow broken her leg? It was that bad! Had her bones become that weak? Had the Cushings advanced to the point where "weak and wobbly" had become much much worse? Had she lost the use of that leg? Was this the beginning of the end?

After a few minutes she settled down. Limped around a little. Went to the loungeroom and assumed the sphinx pose. I lured her forward with some mince meat. The gait was wobbly, but the front right foot was working again.

She had had such a good, quite energetic day last Thursday - I thought I was on the right track - finally. But since then, mostly geriatric again.

Angelina has always loved to rest against something. If you're sitting at a table, you will find ber resting against your foot, or your chair leg, or such. But if you make the slightest move, her self-preservation kicks in, she will over-react, yelp, and make a good attempt at biting your foot. Even if it was only the breeze created by the shifting of your foot, slightly ruffling the hair of her back. Heaven help you if you actually step on her hair! We don't know what would happen if you stepped on her.

It's not surprising - in retrospect - that she would scream the house down upon discovering that her foot had gone to sleep. I hope that's all it was.

My specialist is still missing in action - today I learned he's overseas. "Call me if you have any questions" he says! I'm going to take her in tomorrow, get her electolytes and biochemistry checked out. Probably get an ACTH Stim test done as well if I can. Her liver enzymes have me worried.

The weekend reception can't take appointments - so I'll have to call bright and early tomorrow. Just have to decide if I want to enlist another one of their specialists as well as the resident I've been dealing with.

Since reading Roxee's Dad's thread about good days/bad days on Trilostane, I'm wondering if I jumped the gun by dropping Angelina back to 30mg per day. At 60mg she was good for 3 days - then she was an old dog - now back at 30mg she's become an old dog anyway! Argh!

If I ever meet Mother Nature she will have some explaining to do!

Angelina has developed darkening patches of skin on both sides of her distended lower abdomen (Does anyone know what that might be?) looking like large light bruises.

I was looking at her, once she had calmed down and it seemed as though some of her hair is becoming darker - tanner? Might have been a trick of the light. It only seemed to be happening on the right side of her back.

What a day!

John the Grey