Hola and have a question...

[Oli]

Hello, all...

My wife and I have a Pekingese named Gracie Anne. She is almost 14 years old and has been diagnosed with Cushings Disorder for almost 5 years now (average lifespan of the Cushings furbaby is 2 years, or so I hear). She was on Selegeline until this year and it stopped working, so we switched to Vetoryl. We went up slowly and reached her first 30 day testing at 20mg and got an early Christmas present... the doctor called and said her ACTH was right in the middle of the normal range... perfection. The day after she had her first seizure (petit mal... lasting @ 10s, arms flayed out in front of her and she screamed). As parents we were scared to death... we took her in and the vet said that there was definitely neurological issues (way she walked... back legs not always doing what she wanted them to), but he felt that was due to the Cushings. Being a medical professional of the people type, I agreed... She also has luxating patellas so it is also physical, not just neuro... Anywho... the doctor said he didn't see anything that was damaging, eyes were good, reaction time good, followed commands, etc. He wanted us to watch her for a few days and see if it reoccurred. He did say that it might not have been a seizure but could have also been related to having the ACTH test the previous day with the needles, etc. Since we wanted to believe that... sounded good.

Monday she had another in the morning. This time the Vet that had been working on her Cushings was there. She is a realtively new Veteranarian and was kinda unsure where to go. She said her gait had changed but we are with her all the time. She was walking the best she had in a while. She can even urinate while standing on one (1) leg again... Anyway, the less experienced Vet wants us to go to UGA to have a neurology consult. While I do not think that is absolutely necessary, I feel like we need to do it j.i.c.

Now that you have the back story... now it is time for the question. As I said, I work in a hospital so I started doing a little research into anticonvulsants. I know that phenobarbitol is not a good one with Vetoryl due to liver interaction on the part of both drugs. I am looking at Neurontin (Gabapentin). Neurontin has very few side effects and is not as harsh on the liver. I was wanting to know if any of you had any experience with this particular drug and Vetoryl together?

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[StarDeb55]

Welcome to both you & your little Gracie Anne! What a wonderful life I'm sure that she has had to reach 14. Anyway, I can't offer a lot of help with seizure medication except to say that one of our longtime members, Zoesmom, dealt with both. Sue used potassium bromide pretty successfully with Zoe. Zoe did cross the bridge about a year ago, but she was getting up in years, too. I will post a link to her thread, but it is rather lengthy, so you will have some reading to do. I will also PM Sue, so hopefully she will eventually stop by & offer her input.

http://www.k9cushings.com/forum/showthread.php?t=551&highlight=bromide

Again, welcome! We are here to help in anyway we can.

Debbie

[labblab]

Welcome from me, too! As a mom of a Cushpup (who passed several years ago) and also now a non-Cushpup with seizure disorder, I can sympathize with all of Gracie Ann's issues. My current dog is being treated very successfully with phenobarb, and although concerns about liver toxicity in conjunction with trilostane seem very reasonable, I honestly don't know whether the combination of drugs is actually contraindicated. As Deb has mentioned, the vet of another one of our members preferred to treat her Cushpup with one of the bromides. But we have had at least one other member recently who seems to be successfully using the combo of phenobarb/trilostane. But if phenobarb is not recommended for Gracie Ann, I'd agree with Deb that either potassium or sodium bromide would likely be the most obvious recommendation. In order to obtain the most accurate info re: drug interactions, I'd encourage you to contact the vets who serve as technical representatives for Dechra (manufacturer of Vetoryl, brandname trilostane) in their Kansas office. I'd feel confident that they could give you any relevant info of which they are aware. Here is Dechra's contact info:

http://www.dechra-us.com/Default.aspx?ID=365

As far as the neurological consultation, I certainly wouldn't discourage you from going to Univ. of Georgia. But from my own experience, I know there are some relatively simple blood tests that even a GP vet can perform in terms of identifying possible causes for seizures. However, if your vet is concerned that there is other neurological impairment in addition to the seizures, then the consultation may be especially helpful.

Also, if Gracie Ann has been diagnosed with the pituitary form of Cushing's, I will mention one possible cause for the seizures: over the course of these five years, her pituitary tumor may have been gradually enlarging to the point where it is now placing pressure on other areas of her brain. The only way to diagnose this condition is via a CT scan or MRI of Gracie's head. Both of these procedures are quite expensive, and may or may not be worth pursuing, especially given Gracie's age and available treatment options (most commonly available is conventional radiation treatments over the course of a month). I lost my own Cushpup to what we assume were the effects of an enlarging pituitary tumor, so this is also an area with which I have some familiarity. This testing is performed at both UGA and also the veterinary school at Auburn.

As far as Gracie's Cushing's, I'm glad to hear that the trilostane seems to be working well for her. However, it would be great if you could post her actual monitoring ACTH results because the desired therapeutic range for a Cushpup treated with trilostane is actually somewhat lower than the "normal" range for a dog without the disease. Understandably, Gracie's neurological issues may take precedence right now. But obtaining her test results will help us to also offer feedback and suggestions about her Cushing's treatment, too.

Marianne

[Oli]

I apologize... she does have PDC. That is why I think the seizures are Cushings related due to the increas(ing) size of the tumor. I usually review the lab work for Gracie Anne and it was within limits. As I said... I am still debating the Neuro consult, but it is likely I wouldn't do the MRI, only because we have no baseline for the original size of the tumor, I would rather not put her through that (I think it would scare her and I feel she has been through quite enough). I have considered speaking with the first Vet, with the most experience, and ask him for a second opinion. As I said... the newest Vet said she saw a definitive difference in Gracie Anne's gait... and we did too... it was the best she has walked in over six (6) months. She now walks around with her chest out and does this little prancing/prissy walk thing. Since the Vetoryl has been started we have seen a dramatic change in her demeanor and behaviour for the better.

I read up a little on Sodium Bromide and Potassium Bromide. From what I read Sodium Bromide can be more difficult on the body than Potassium Bromide. Like I said in the above paragraph, I am thinking about asking for a second opinion from a more experienced Vet and the possibility of starting her on an anticonvulsant. I am really interested in Neurontin (Gabapentin), but would like to hear of some other options. Phenobarbitol is not something Gracie Anne cannot have but it would require some change in her dosage of Vetoryl. With her current happy-go-lucky actions I hate to change that. Also... the seizures... she has had 3 lasting no more than about 5 to 10s and afterwards she goes about her business as if nothing has happened. She even started "itchy-facing" on the bed right after her second one...

[lulusmom]

Hi and welcome to the forum.

How many seizures has Gracie Anne had and how far apart were they. My little cushdog, Lulu, has infrequent seizures. As a matter of fact, she had one about an hour ago. She hadn't had one for about a month. She too has the petit mal type which lasts anywhere from 2 to 10 minutes. Her last one was about a month ago. She's had these for the last three years and unless she starts having them frequently, I will not put her on meds for it. She is being treated with Lysodren.

In our experience, it does seem that the Brachycephalic breeds tend to be over represented relative to macro tumors. Selegeline tends to work for the small number of dogs with tumors in the pars intermedia lobe of the pituitary or those with a mild form of the disease. Efficacy is only about 20% so you are lucky that Gracie Anne responded so well and for so long. Unfortunately, if the tumor expands into other areas, the drug becomes ineffective so that might be more evidence of an expanding macro tumor.

You mentioned that your vet said the last ACTH stimulation test results were within the normal range. I'm not sure what normal range your vet is using but normal reference range used by the lab is not normal for purposes of monitoring treatment. The objective of treatment is to reduce the post stimulated cortisol level within the basal reference range of 1 ug/dl to 5 ug/dl but if symptoms have resolved, the manufacturer of Vetoryl indicates that a post stim of 9 ug/dl is acceptable. UC Davis, who has done their own clinical studies, does not agree and wants the post stimulated number to be below 5 ug/dl.

Can you please post the results of the ACTH stim test?

Glynda

[Oli]

I can get her results in the morning. I am at the hospital at the moment. She has had 3 seizures. The first was the day after her ACTH test. It lasted approximately 5 to 10 seconds afterwhich she was rolling around and wanting to play. The second seizure was Monday of this week (12.26.2011). It lasted about the same amount of time... and afterward she was rolling around scratching her back and going after her little brother. The third was later that evening around 2245... it was about the same as the others. She has not had one (knock on wood or whatever proverbial substance you wish) since then and we have noticed no neurological deficiencies other than what she already had, to which have improved since we have got her on a therapeutic dose of Vetoryl.

[Oli]

OH... on a lighter note... I mentioned a brother... Gracie Anne has two (2). She has Rusty (almost 14 year old Pekingese... about 1.5 months older than Gracie Anne) and Eli Noah (Pug). She gives Eli hell... but he is a mischievous little boy too... so he deserves it sometimes...

:)

[labblab]

Phenobarbitol is not something Gracie Anne cannot have but it would require some change in her dosage of Vetoryl. With her current happy-go-lucky actions I hate to change that.

Can you tell us what Vetoryl dosage adjustment would be required, and also the source of this info? For a while now, I've been really interested to find out whether there are indeed interaction/potentiation effects associated with the combination of phenobarb and trilostane. That's why I suggested earlier that you might want to contact Dechra, although I guess there's no reason why I can't check with Dechra myself, right? ;)

Also, you may already know this, but even though gabapentin is not metabolized by the liver in humans, apparently it is partially metabolized by the liver in canines. So if you are wanting an anticonvulsant that has no liver involvement at all, potassium bromide might still be the most likely candidate. Additionally, there may be newer research available, but from these two articles discussing gabapentin as "add-on" therapy, it sounds as though a couple of downsides to gabapentin are the very short half-life and also the fact that a significant number of dogs just don't appear to be responsive to it.

http://veterinarymedicine.dvm360.com/vetmed/article/articleDetail.jsp?id=608398&pageID=1&sk=&date=

http://veterinarynews.dvm360.com/dvm/Medicine/New-anticonvulsant-drugs-show-promise-in-dogs-cats/ArticleStandard/Article/detail/501084

Marianne

[labblab]

OK, I just spoke with one of Dechra's technical reps, and what he told me pretty much coincides with what you were already thinking. Even though there is no documented interaction between trilostane and phenobarb (he is unaware of any clinical trials that specifically addressed that drug combination), dogs who are being treated with both drugs need to be monotored very diligently both in terms of liver function and also trilostane efficacy. He is aware of dogs that are currently being treated with both drugs, and no particular problems have surfaced thus far. But theoretically, phenobarb's effect on the liver could alter the way in which trilostane is metabolized by any given dog, leading to the potential for trilostane overdosing in the absence of appropriate dosing adjustments. Everything being equal, potassium bromide would probably be a preferable treatment choice for a dog suffering from both conditions. I'm sorry, but I forgot to ask about gabapentin :o.

This is just my own opinion, but if my own sweet "seizure-girl" were to now develop Cushing's, I might be inclined to leave her on the phenobarb because she has done amazingly well with it (knock on my wooden head!!). But if I had a Cushpup on trilostane who was newly diagnosed with seizures (like you guys), I'd also be looking at alternatives such as potassium bromide. Oh, in that regard, I also asked whether there would be a preference in a Cushpup between potassium bromide and sodium bromide (due to potential effects on electrolytes), and he said it was a good question but one for which he is unaware of an answer. He suggested asking a neurologist about that one.

Marianne

[Oli]

Update on Gracie Anne... We went to UGA for the Neuro consult and discovered something that had never crossed my mind. Gracie Anne has hypertension... The episodes that appeared to be really short siezures were actually syncopal episodes that occurred from extremely high blood pressure. We ended up staying overnight in Athens to get some serial blood pressure readings. Her initial readings were 270/120... 275/108, etc. She has been put on Amlodipine (Norvasc) for her blood pressure and it has been monitored. Her blood pressures are running around 100/80 or 100/70 at the moment and she is bouncing around like a puppy sometimes. We split her dose of Trilostane and her numbers came up perfect. I think we have resolved Ms. Gracie Anne's issues... My wife and I thank you for your support in this whole ordeal... Just thought you mates might want an update...

[Rebelsmom]

Thanks for the updates. Please keep us informed of how she does we would love to hear.