New member - hello, need some advice pls (Maltese) Trilostane

[Clyde]

Hi everyone, I have read many of your stories with interest in the past, but have only just registered to join your forum as my vet seems to be going in circles with no real answers. I am hoping someone can help us with some fresh ideas...............here is our Cushings story:
Our Maltese (Clyde) weighing 6kgs, was diagnosed with Cushings in 2008, aged 8 years. He was prescribed 30mgs Trilostane per day and remained stable with regular tests for over 3 years.
On 3 Dec 2011 (aged 11) his Cushings test reading was 118. A blood test also 3 Dec showed ALKP levels >2000U/L. Concerns over his liver function lead to an ultra sound to check his organs on 7 Dec. No abnormalities were detected. A urine sample ruled out diabetes. At the same time a suspicious surface lump was removed from his left lateral chest wall, 6mm in diameter – diagnosis cutaneous extramedullary plasmacytoma, the vet had no further concerns with the diagnosis.
With no apparent explanation for the elevated Cushings levels and blood tests, Clyde’s Trilostane dose was increased to 45mgs per day. Cushings test on 5 Jan showed further elevated levels of 139-155. Trilostane dose was increased again to 60mgs daily and Cushings test on 25 Jan again elevated to 112-163.
Clyde’s physical condition throughout all of these changes remained stable. He is a happy, relatively fit, somewhat active and healthy dog. His daily water intake perhaps a little high around 600-700mls, he loves his food and eats all meals quickly. We decided at this point to ‘leave things alone’ and have a break. It seemed that all major tests and concerns had been eliminated, so we let things be for a few months.
Two weeks ago (May 2011), we increased his Trilostane dosage levels to 70mgs under discussion with our vet. Another Cushings test has revealed a further increase in levels to 110-330.
Our vet has no explanation at this point, other than to increase his Trilostane to 80mgs.
Is there something our vet is missing???? Or something else we need to have checked????? He is quite a nervous dog......is it possible that his increased anxiety at the vet may be contributing to these elevated results each time???? His anxiousness seems to be increasing with his age lately.
At this stage, it looks like his Trilostane dosage levels will just keep increasing, yet having minimal effect on his Cushings levels...............how much Trilostane can a 6kg dog take safely? He appears to be a happy, fit and healthy dog (for his age), although rather nervous at times ..............if anyone can please help with some new ideas..................Thanks, Clyde

[mytil]

Hi and welcome to our site.

I am sorry but I do not have direct experience with Trilostane, but I do have several comments - a 6 kilo taking 70mgs of Trilostane sounds too high of a level to me. And there should be letters after the numbers from the ACTH testing (ug/dl or nmol) which one does your indicate?

Take a look at this link that provides additional information about Trilostane dosing and monitoring. http://www.k9cushings.com/forum/showthread.php?t=185

Terry

[frijole]

Welcome from me as well. You mentioned that the liver enzyme values remain elevated but I did not see results from the acth test which is used to monitor cortisol levels which is what you are trying to decrease. Are you having acth tests done? If so, posting those results would be helpful.

On the alk phos levels - cush dogs probably will never have normal range levels but they should go down. Perhaps there is something else going on. Many, including myself, have given milk thistle as a supplement to help with liver values. My experience was that my dog's levels went from 1800 to 800.

Regardless, the focus was on the cortisol level and the acth tests are used to monitor it. Any changes in trilostane should be based on the acth results. That is a mighty high dosage for a wee little thing.

Kim

[littleone1]

Corky and I also want to welcome you and Clyde.

Corky's been taking Trilostane for 19 1/2 months. His dosage has had to be increased, but the increases result in lower cortisol levels. Corky weighs 18.3 pounds and he is now taking 60mg of Trilo a day.

I'm not good at metrics, so I don't really know how many pounds 6kg would be. There is always a possibility that stress can cause some increase to cortisol levels, but it does seem strange the Clyde's level keeps increasing with higher dosages.

I don't have any answers for you, but I'm hoping that someone will be able to shed some light on this for you.

Terri

[Harley PoMMom]

Hi and welcome from me as well!

I agree, too, that 70-80mg of Trilostane seems high for a dog weighing 6kg or 13.2lbs.

According to Dechra's Product Insert a dog's cortisol can be as high as 9.1ug/dl or 250nmol/L with no dosage increase as long as the clinical signs are controlled. You can find this information here: Dechra's U.S. Product Insert. (http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf)

Is Clyde displaying any Cushing symptoms? As far as the liver enzyme, ALP, some dog's ALP never do fall within the normal ranges even if their cortisol is within the normal therapeutic ranges. Many other issues can elevate the ALP. How are Clyde's ALT levels? The ALT is a more specific liver enzyme than the ALP.

Love and hugs,
Lori

[Clyde]

Welcome from me as well. You mentioned that the liver enzyme values remain elevated but I did not see results from the acth test which is used to monitor cortisol levels which is what you are trying to decrease. Are you having acth tests done? If so, posting those results would be helpful.

On the alk phos levels - cush dogs probably will never have normal range levels but they should go down. Perhaps there is something else going on. Many, including myself, have given milk thistle as a supplement to help with liver values. My experience was that my dog's levels went from 1800 to 800.

Regardless, the focus was on the cortisol level and the acth tests are used to monitor it. Any changes in trilostane should be based on the acth results. That is a mighty high dosage for a wee little thing.

Kim

Hi Kim
Thanks so much for your kindness and reply. I am interested in using milk thistle..........do you have a guide to the dosage amount?? I assume it is the same milk thistle available in pharmacies/chemist supplies? Many thanks, Clyde

[lulusmom]

Hi and welcome from me too.

First let me say that Clyde is adorable. I love the breed and have two Maltese boys myself. Fortunately they don't have cushing's but my two Pomeranians do.

I remember reading somewhere that dogs can build up a resistance to trilostane with long term use. I just did a quick search and did find one source that confirmed that. It's a lecture given by Dr. Patty Lathan, DVM, ACVIM at the Central Veterinary Conference in Kansas City. It's a long article but there is one sentence in there that says "The dose of trilostane may need to be increased, as patients seem to get more resistant to it with time." I believe this may be what is happening to Clyde.

http://veterinarycalendar.dvm360.com/avhc/article/articleDetail.jsp?id=650450&sk=&date=&pageID

I know 80mg sounds like a huge dose for a 6kg dog but sometimes dogs will require multiple increase in dose that is ultimately 10 times the amount of the starting dose. Every dog is difference so you just never know. As a frame of reference, one of my cushdogs weighs 2kg and she was taking 30mg Trilostane once a day. That equals 15mg/kg. If you raise Clyde's dose to 80mg, that would be equal to approximately 13.33mg/kg. Whether Clyde will continue to be resistant to the drug, I have no idea but I bet Dechra, the manufacturer or Vetoryl, could tell you. I assume that since Vetoryl is not approved for use in Australia that Clyde is taking compounded Trilostane, right? We've had members on compounded Trilostane contact Dechra so you or your vet could contact either the U.S. or the U.K. divisions and ask them if it is likely that Clyde will continue to be resistant. Here is the contact information:

http://www.dechra-us.com/Contact-us-1.aspx
http://www.dechra.co.uk/contact-us.aspx

Glynda

[Clyde]

Thanks so much for this information. I know that many people think the dose is already quite high, but he is/and has coped with this amount over a period of time now with no apparent side effects. This makes me feel a little more comfortable. Many thanks. Clyde

[Clyde]

Thanks for your reply and interest.
Clyde's ACTH simulation test results a few days ago were:
110 nmol/L cortisol resting and
331 nmol/L cortisol, l hour.

A blood test today has given similar readings to blood tests 6 months ago with high readings for:
ALKP 3919 U/L (23-212)
HCT 58.9% (37-55)
HGB 19.0 g/dL (12-18)
ALT 133 U/L (10-100)
all other blood readings were in the normal range.

It has been recommended to repeat another ultrasound examination next week.
As I said earlier, we are going in circles again - same pattern occured 6 months ago, with nil abnormalities or explanations given for the high levels.............does anyone have any other ideas?
Clyde's general health and clinical signs continue to be good. Increased Trilostane does not appear to be having much effect on these readings.

[Clyde]

Thanks Glynda
Pleased to hear that some dogs require higher doses of Trilostane - seems to be the direction we are heading. However, the ACTH reading of 331 nmol/L a few days ago is way out of range....further investigation is needed (again). Will let you know the results of more tests this week. Clyde

[labblab]

Thanks for this additional information. I had suspected yesterday that the ACTH readings you had provided were in units of nmol/L. I had started to do the conversions for our U.S. readers last night, but I got sidetracked :o. But here they are -- I think I've got the history transcribed accurately (and the conversion formula is to divide the nmol/L result by 27.59). To start off, Clyde had been maintained consistently on 30 mg. of trilostane for three years. At that point:
______________________________________________

3 December 2010: post-ACTH 4.27 ug/dl (trilostane subsequently increased to 45 mg.)

5 January 2010: post-ACTH 5.62 ug/dl (trilostane subsequently increased to 60 mg.)

25 January 2010: post-ACTH 5.91 ug/dl (dosage remained at 60 mg.)

Two weeks ago, dosage increased to 70 mg.

Current post-ACTH 11.96 ug/dl
_______________________________________________

I do have a couple of questions. First, were Clyde's previous ACTH results (while stabilized on the 30 mg.) all lower than last December's reading? I'm just wondering, because that result (118 mnol/L or 4.27 ug/dl) is still within the ideal therapeutic range for a dog being treated with trilostane. However, you describe that result as being "elevated" for Clyde, which factored into the decision to increase his dose at that time.

Clyde subsequently had additional dosing increases which, until May, had still kept his test results largely within therapeutic range, and not hugely variable (4.27 ug/dl - 5.9 ug/dl). It's not until this most recent test that we see the big jump (to 330 mnol/L or 11.9 ug/dl).
Throughout all this time, however, it sounds as though Clyde has been doing well, behaviorally. Would it be fair to say that it is the laboratory abnormalities (particularly the ALKP) that have been of greater concern since last winter? I do wonder whether there is something else, unrelated, that is going on that is fueling that huge increase in the ALKP.

One last question: have the previous ultrasound images supplied information to indicate whether Clyde suffers from pituitary vs. adrenal Cushing's? I guess that's the one additional thought that I could offer out in terms of ever-increasing demands for dosing increases...if Clyde does suffer from an adrenal tumor, perhaps that is now "ramping up" the overproduction of cortisol. Just an idle thought...

Marianne

[Clyde]

Thank you so much for taking the time and interest to consider our situation. Your sumation of events is correct. Did the current blood results shed any further ideas? Yes, you are correct, the vet feels they are missing something else................another ultrasound is scheduled for later this week (having carried out all these tests 6months ago). I can't remember which type of cushings he has (I was told many years ago), but it was the most common type, I will ask next time I talk to them..............I have electronic copies of his ultrasound pics from Dec 10 if you are interested. These ultrasound pics will be compared to the new pics later this week. Thanks again for your information. I turned to this forum for some guidance and advice - it has been great.......amazing technology from one side of the world to another. I'm still finding my way through the use of the forum. Clyde:)

[Clyde]

Hi Marianne
I did not answer all your previous questions:
Clydes ACTH post result - June 2008 on 30mgs Trilostane was 53nmol/L - the vet considered this result to be 'ideal'. I did not keep the results for the next 3 years, although I believe they slowly increased from this point. Yes, the results have been lower in the past....the vet considered the test in Dec 2010 to be a bit high and as you can see, this trend has continued even though the Trilostan dose has increased.

Your idea is probably correct. I recall a comment last Dec that his adrenal glands were quite large..........

RAdrenal gland: cranial pole .94cm(w) x 2.26cm(l), caudal pole .78cm(w) x 1.18cm(l)
LAdrenal gland: cranial pole 1.0cm, caudal pole .58cm(w) x 2.65cm(l)
Spleen - multiple regular well circumscribed hyper echoic parenchymal lesions
Both Kidneys -NAD
Liver - generally moderately enlarged and hypo echoic. NAD

Summary Comments on ultrasound Dec 2010:
Splenic lesions most lidely hyperplastic.
Marked bilateral adrenomegaly however non symmetrical within each gland - suspect benign cortisol secreting microtumers.
Hepatomegaly and parenchymal lesions consistent with vacular hepathopathy associated with hyper cortisolaemia.

Clyde

[Clyde]

Another ultrasound (6months since the last) has revealed little or no change. The vet is comfortable that further tests are not required at this stage. An explanation for the ACTH 331 reading indicates that the Trilostane is no longer effective, and it would be unwise to continue to increase the dosage................I am pleased to hear that!

We will trial a new drug (I think it was vetoryl), but will check when picking it up next week. Unfortunately dosage only avail in 30mg and 60mg, so we will start with the larger amount. Fingers crossed this will bring his levels under control again???? I am also told that this drug is more expensive than Trilostane...............would be happy to hear other similar experiences or advice, thanks

[labblab]

Hello again!

Hmmmmm...I confess to being puzzled by the information that your vet is giving you about Clyde's medication. This is because "trilostane" is the identical active chemical that is contained in Vetoryl. So you will still be giving Clyde the same drug. The only difference is that you will now be giving him the brandname version (Vetoryl) rather than a compounded version (which is apparently what he had been receiving in the past).

It is interesting that your vet is raising a question about the effectiveness of the trilostane that Clyde has been taking thus far. By any chance, was it in a liquid form? A few other members here have used liquid suspensions rather than capsules/tablets, and I have often wondered whether the liquids retain their effectiveness for as long a time. At any rate, I am curious as to how your vet has determined that the compounded version is no longer working for Clyde.

For more information about Vetoryl/trilostane in general, take a look at this link:

http://www.k9cushings.com/forum/showthread.php?t=185

One of the replies on that thread discusses the difference between brand-name versions of drugs as opposed to compounded versions. I will also come back and add a link to another thread here on the Q & D forum that discusses some of the differences between the two forms of the drug. We do have members here who successfully use brand-name Vetoryl, and we also have members who successfully use compounded trilostane. So I'll come back and add that link in a moment.

Marianne

P.S. OK, I'm back again with that additional link. As you will see, we talk about U.S. regulatory issues in this thread, which will not be directly applicable to you in Australia. But the basic thrust of the conversation is the same in terms of the difference between the brand-name version of the drug (imported from the U.K.) and compounded versions (prepared by individual pharmacies).

http://www.k9cushings.com/forum/showthread.php?t=3223

[jani]

Hi,

Look into this supplement called Relora. It made a huge difference in my dog Maisie. You find it at the health food stores. It helps curb cortisol. My vet said it was ok....but always check with your vet as well.

good luck with everything,
jani

[Clyde]

Hi Marianne
Thanks for the information and links - I now understand what a 'compounded' chemical is. Yes, I can see that the other brand maynot be effective since it is the same.......

Clyde has been taking Trilostane capsules (not liquid) for several years now (stable for 3 years), but requiring increasing amounts in the last year, with no apparent side effects. Current ACTH figures not acceptable, not keen to keep pumping up the trilostane at this stage.

Our vet contacted a specialist who suggested trialling the non-compounded drug................not sure what other options are available if this proves ineffective???

Thanks again for your advice, will contact again when we trial the other brand.

Debbie & Clyde

[labblab]

Dear Debbie,

It will definitely be interesting to see whether or not Clyde responds more favorably to the brand-name Vetoryl. However, in the event that it does not work any more effectively, there is one other medication option that ought to be available to you: Lysodren (the chemical name for the drug is "mitotane").

Lysodren was the drug-of-choice for treatment of canine Cushing's here in the U.S. prior to the introduction of Vetoryl (trilostane), and many vets still choose to prescribe it for their Cushing's patients. It is not available for use in the U.K., but I do believe that it remains available in Australia (hopefully another Australian member can confirm that for us).

The mechanism of action is entirely different for Lysodren vs. trilostane. Lysodren provides cortisol reduction through the selective erosion of layers of the adrenal cortex. Dogs being treated with Lysodren first go through a "loading" phase in which they are given daily doses of the drug to achieve the desired level of erosion (verified through ACTH testing). Once the erosion is complete, then the dog moves to an ongoing "maintenance" phase of treatment during which time the dosing is instead spread out over a period of days in order to control adrenal regrowth.

If you look through other threads on this forum, you will find many members who are actively treating their dogs with Lysodren. First things first -- we will hope that the shift to Vetoryl will solve Clyde's problem. But if not, I just wanted you to be aware that there should be at least one other alternative that would be available to you.

Marianne

[Clyde]

Oh my goodness - what wonderful (surprising) results......this information might warrant a NEW THREAD for further investigation.

To recap Clyde on Trilostane 3-4 years.
Stable for 3 years, thence increasing Trilostane doses required, but no longer as effective:
May 2011 - 6kg maltese, age 11 - 70mg Trilostane
ACTH results
cortisol resting 110 nmol/L
cortisol 1 hour 331 nmol/L

June 2011 - after 12 days on 60mg Vetoryl
ACTH results
cortisol resting 85 nmol/L
cortisol 1 hour 39 nmol/L

We are so happy, these are the BEST results we have ever had for Clyde. Our Vet is also a bit shocked with the results. Although Vetoryl is twice the price of Trilostane, it is working for us!

This poses a few questions for all cushings dog owners........

Clyde

[Harley PoMMom]

June 2011 - after 12 days on 60mg Vetoryl
ACTH results
cortisol resting 85 nmol/L
cortisol 1 hour 39 nmol/L

Clyde

Dear Debbie,

Just a word of caution, in Dechra's product insert they advise that if the dog's cortisol drops below 40 nmol/L that Vetoryl be stopped and restarted at a decreased dose. Here is a link about this: http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf

Low cortisol symptoms include diarrhea, vomiting, lethargy and/or Clyde not acting himself.

Please keep us posted.

Love and hugs,
Lori

[Clyde]

Thanks for your concern.............it is interesting that both our local vets work towards a post ACTH level around 50nmol/L and the lab report suggests a 'normal' range of 28-55nmol/L.

In any case, Clyde's physical condition is very good, with no obvious problems encountered. My vet also tells me that VETORYL is only available in 30mg and 60mg capsules in Australia, so to change the dose poses another problem........

Thank you again for reminding me to continue to monitor Clyde's physical condition.

My main interest in posting these results was to highlight the fact that Trilostane is NOT the same as VETORYL. I thought the forum readers would find this interesting......particularly if (like Clyde) after a 3yr stable period, Clyde was no longer responding effectively to the Trilostane..............Clyde's favourable reaction to VETORYL was quite remarkable after 10 days..........

Debbie

[labblab]

I am delighted to hear that Clyde is responding so well to the Vetoryl, but I must also echo Lori's concern about the level of his ACTH results after only 12 days on this medication. For the benefit of our U.S. readers, Clyde's ACTH result converts into 3.1 ug/dl (pre) and 1.4 ug/dl (post). I am very puzzled by the lab "norms" that you have been given, because they do not correspond in any way to the published treatment and monitoring protocol of Dechra, the manufacturers of Vetoryl. Their ideal therapeutic range for a dog being treated with Vetoryl is 40-150 nmol/L. And they also warn that cortisol levels may likely continue to drift downward during the first 30 days when the medication is started or when a dosing change is made. So Clyde is already below their recommended "basement" (just barely), and we may expect that he'll fall even lower over the next couple of weeks. So I am very concerned that this dose of Vetoryl will prove to be too high for him.

As you have noted, this does provide a dilemma for you since you cannot obtain the 10 mg. Vetoryl capsules in Australia. However, if Clyde does need a dose that falls between the 30 and 60 mg. capsule strength, perhaps you can find a compounding pharmacy that will "repackage" your already purchased Vetoryl capsules into smaller units. This is a different situation from purchasing compounded trilostane, per se, in which the active ingredient may be sourced from any bulk pharmaceutical supplier in the world as opposed to the documented, approved supplier that is used by Dechra in the manufacture of Vetoryl.

Your experience highlights concern that I have personally felt about compounded trilostane usage. It is not that a compounded product will make a dog ill, but I worry that the effectiveness of the product may vary from batch to batch or capsule to capsule due to the fact that it is being prepared onsite by an individual pharmacy using ingredients from their personal suppliers rather than according to the established protocols required of a formal drug manufacturer that is making a brandname med or a true generic equivalent (compounded drugs are not the same thing as generics).

However, in cases where a dog requires a dose that is not available in Vetoryl, then compounding pharmacies serve a hugely important service. Also, the realities of the cost of brand-name Vetoryl may place it outside of the reach of many owners. In that case, less expensive compounded trilostane may be the only viable treatment option that is available to an owner. We do have many members who have used compounded trilostane (not using Vetoryl as the base) for lengthy periods of time with good results. They have been very pleased with both the professionalism and also the apparent quality of their compounding pharmacies.

I, myself, have used some compounded products over the years. But when availability and expense permits, my personal preference is to first begin by using the brandname version in order to establish a "baseline" expectation as to how the drug will affect me (or my dog). If I then notice no therapeutic difference after switching to a compounded version, I feel more comfortable that the compounded drug is equally as effective. But as I said above, sometimes that is not a reasonable option for an owner.

The bottom line is that I am very glad that Clyde is responding so well. But I am very concerned that you may need to find a way to reduce his current Vetoryl dose by finding a pharmacy that will repackage it for you. Please do keep us updated.

Marianne