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  #1  
Old 04-20-2009, 08:51 PM
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4Mikeydog 4Mikeydog is offline
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Default Mikey no longer doing well on Trilostane

I am so glad I found you!! My 8 1/2 year old miniature poodle, Mikey was diagnosed with pituitary dependent cushings last March after an ACTH stim test with results:
pre 4.3 and post 39.7 and an ultrasound.
He had most of the classic symptoms; excessive thirst, excessive urinating, ravenous appetite, weak hindquarters, potbelly, and lethargy. He had a dull coat which had gone from a beautiful apricot color to a pale shade of cream, but no visible hair loss...
Mikey was put on Trilostane 30 mg 1x per day and within 2 weeks most of his symptoms started to subside.
All subsequent ACTH tests show effective management of cortisol. Mikey was his old self for quite awhile
However..after 5 months on Trilostane, my sweet guy began to lose hair at the tops of his ears and on his tail. This hair loss has continued.
Trilostane remained at 30mg 1x per day until some adjustments due to trembling and lethargy.
Mikey is presently on Trilostane 10mg BID. He has continued to lose hair, weight and muscle mass. He has an underlying intestinal or absorption problem which is currently being mediated.
His IM specialist ordered the UTK adrenal panel 3/30/09.
The results are as follows:

Cortisol Pre 8.3 ng/ml Post 48.1 ng/ml

Androstenedione Pre 0.90 ng/ml Post 0.70 ng/ml

Estradiol Pre 85.6 pg/ml Post 82.6 ng/ml

Progesterone Pre 1.00 ng/ml Post 1.70 ng/ml

17 OH Progesrerone Pre 4.89 ng/ml Post 6.77 ng/ml

Aldosterone Pre 21.6 pg/ml Post 37.9 pg/ml

Androstenedione, Estradiol, Progesterone, and 17 OH progesterone are all elevated.
I've read enough to know that Trilostane can do this.
Today we met with the IM specialist who is taking over for his original dr who is out on maternity leave..
I am truly confused and upset.
Clinically all signs of urinating, drinking, and appetite are mediated. However Mikey is lethargic, has lost most of his hair and is down to 12 lbs (poor guy)!
The vet initially recommended increasing the Trilostane
I commented that I thought melatonin,
flaxseed oil with lignans and or a maintenance dose of lysodren may be a better choice.
The specialist said we could do that and suggested 5 mg of melatonin BID first with Trilostane as is..
Then if I wanted to introduce the maintenance dose of Lysodren, I should stop Trilostane for 2 weeks and then start a maintenence dose of Lysodren. I'm very alarmed about this because I don't know if the Trilostane will really be out of his system enough to do this safely...
The IM specialist said that if we wait the 30 days without Trilostane we will have to actually load him instead. My questions are as follows:
What is your experience with this concept?
What have you experienced in switching a dog from one treatment to another?
Do you have any recommendations for how to start treatment with melatonin?
Do you think the 5mg melatonin BID is too high a dose for a 12 lb dog?
I am sorry if I am rambling..but I am truly frantic!

Thanks,
Dorothy and Mikey
  #2  
Old 04-21-2009, 04:59 AM
frijole frijole is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorothy. I'm not sure how long is best to wait before switching from trilostane to lysodren... seems like it is less than 30 days but I am bumping this up so someone will read it and get back to you.

I'm glad you found us!

Kim
  #3  
Old 04-21-2009, 05:19 AM
we3dogs we3dogs is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorothy - I don't have an answer for you and do not know about test results but wanted you to know that I am thinking of you and Mikey. My Angel is having issues with trilostane as well that began last fall. She's been on trilo for 2.5 years. I certainly feel your frustration! And feel free to ramble on - we've all done it and it is sometimes in those streams of thought that we discover something important! Take care - Joyce, Pebbles & Angel
  #4  
Old 04-21-2009, 05:20 AM
barney's mom barney's mom is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi,
I had to switch my dog from Trilo to Lysodren. I want to say it is a 30 day wash out and you load on a much lower dose. It went very smoothy. I also had hair regrowth on Lysodren that I didn't have when he was on Trilo. To be fair he was only on Trilo a few months. I will see if I can't find the specifics for you.



Cheryl
  #5  
Old 04-21-2009, 06:26 AM
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Roxee'sDad Roxee'sDad is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorthy,
First I would like to welcome you and Mikey. You will find a lot of help here. I believe it was Glynda that seemed to have the same problem or very similiar. That is when she found out about atypical cushings. I am not sure myself about this and your UTK results but I hope she will check in soon and maybe help you sort this out.
Hope for the best for you am Mikey.
John (Roxee's Dad)
  #6  
Old 04-21-2009, 07:07 AM
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Lulusmom Lulusmom is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorothy,

I switched both of my cushdogs from Trilostane to Lysodren. They are both Pomeranians (4.5 lbs and 8 lbs) and like your Mikey, they are a breed that is over represented when it comes to adrenal hormone imbalances. They should have never been placed on Trilostane without having a UTK adrenal panel done. After two years of treatment, Lulu's sex hormones had skyrocketed and I took both off of Trilostane immediately.

You are correct in that there is no way for you to tell if the elevation in the other adrenal hormones is due strictly to the Trilostane or if Mikey already had an imbalance and Trilostane has exacerbated the problem. In order for you to have correctly determined this, Mikey should have been taken off the Trilostane for at least 30 days before an adrenal panel. It is also very important that you go through a minimum 30 day washout period when transitioning to Lysodren. In our case, I waited until they were symptomatic again, plus we had acth stim tests done to make sure that cortisol levels were above 22ug/dl before loading with Lysodren.

With Mikey's very high post stim number before starting treatment, I don't believe that it is going to be possible to transition from Trilostane to Lysodren without loading. The two drugs work very, very differently...Trilostane is an enzyme blocker which over time actually enlarges the adrenal glands whereas Lysodren shrinks the adrenals as it erodes the adrenal cortex to a point where they no longer oversecrete cortisol and in most cases, the sex hormones. Maintenance doses of Lysodren given with melatonin and flaxseed can be effective in reducing cortisol in dogs with mild cortisol elevation but Mikey doesn't have mild elevations so I would be very surprised if this treatment regimen is the right one for Mikey.

My Lulu lost 3/4 lb and with a starting weight of under 5.5 lbs, that was pretty significant. I wrote to Dr. Oliver at UTK and asked him if he had experienced this phenomenon with other atypical dogs. He said yes, weight loss can be due to the excess sex hormones. I would very much like to hear how your IM was able to pinpoint the absorption problem with Mikey. Other members have also reported weight loss in their pups while having a very healthy appetite. It is very difficult to watch your dog lose weight and not know why it's happening.

According to the UTK adrenal panel, Mikey's cortisol is being controlled by the Trilostane so like you, I am very confused as to why your IM would suggest increasing the Trilostane.

My IM consulted with Dr. Oliver at UTK to discuss the best approach to Lulu's treatment. It was mutually agreed that Trilostane should be discontinued and treatment with Lysodren be started after an appropriate washout period. Perhaps you might suggest that your IM consult with Dr. Oliver too.

I hope this helps.

Glynda

Last edited by Lulusmom; 04-21-2009 at 07:14 AM.
  #7  
Old 04-21-2009, 12:39 PM
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Squirt's Mom Squirt's Mom is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorothy,

Glad you and Mickey found us here! But wish it was with better news on Mickey.

Glynda has covered the bases expertly as always. I would like to address the melatonin dose recommended, tho. Dr O has Squirt on 3mg 2x/day and she weighs about 14lbs. I think the 5mg is too much for Mickey personally. This is from the treatment sheet provided by UTK:

"2) Melatonin. Often used as a first treatment, especially if alopecia is present, since it is cheap, has few side effects and is available in health food stores or via nutrient suppliers on the Internet.
Typically, a total dose of 3 mg is given q12hrs (BID) for dogs <30 lbs; a total dose of 6 mg is given q12hrs (BID) for dogs > 30 lbs. Regular melatonin is usually used rather than rapid release or extended release products. Melatonin has anti-gonadotropic activity (effective for ferret adrenal
disease), and it inhibits aromatase enzyme (decreases androstenedione and testosterone conversion into estradiol) and 21-hydroxylase enzyme (effectively lowers cortisol level). Monitor treatment effectiveness by improvement in clinical signs, biochemistries or by repeat of steroid profile.
"

You can find this sheet at:

http://www.vet.utk.edu/diagnostic/en...ushing%27s.pdf

Hope this helps.
Hugs,
Leslie and the girls
  #8  
Old 04-21-2009, 07:17 PM
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4Mikeydog 4Mikeydog is offline
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Default Re: Mikey no longer doing well on Trilostane

Thank You so much for your kind words of support and encouragement....and especially for sharing your knowledge. Glynda, my heart breaks when I hear about your dear Lulu. I can wholeheartedly relate to your pain.
My dear sweet dogboy is fading away to nothing. He is skin and bones
We have tried different diets and all kinds of testing throughout the past 4 months....
Mikey presented at his initial diagnosis of cushings weighing 20 lbs!
He was quite overweight, as his usual weight was between 15 and 16 lbs.
So when he reached 16 lbs again after 5 months of Trilostane, we certainly were not alarmed. However, his weight loss has drastically continued.

Of particular interest was how an intestinal manifestation presented itself immediately after an ACTH stim test administered 11/21/08.
Up until that point, Mikey had only 1 issue with diarrhea in the past, was medicated with metronidazole and made a complete recovery. He had never had a reaction to an ACTH stim test in the past.

After this particular Acth test in Nov, within 1 hr of returning home, Mikey began to vomit recurrently. He could not hold down water and had absolutely no interest in food, as he was probably nauseus. He vomited 5 times within 2 hrs and went back to the vet's office, where he was administered subcutaneous fluids, injectable prednesone , and injectable anti-emedics.
Within 3 hrs, Mikey was back to himself...supposedly.
Two days later, continuous diarrhea began.
Mikey, ultimately, was put on a diet of boiled chicken breast and brown rice as well as metronidizole 50 mg BID.
Mikey remains on this dose of metronidizole until presently because each time the medication is stopped, the diarrhea returns within 3 days.

He has been tested for parasites twice and the results have been negative.
He has been prophylactically dewormed with Pancur.
He is only able to tolerate the boiled chicken breast, brown rice, and the switch from science diet to...Nutro dog food with chicken meal, brown rice, and oatmeal for sensitive stomachs...(uh oh, I read about the FDA investigation of this company yesterday and now will change this)
His bowel movements are fully formed but soft on this regiment.
This is much better than the yellow soup he has had in the past.

I wondered why this seemed to happen directly after this particular ACTH test. It didn't seem like a coincidence. He has had so many of these tests uneventfully in the past.

Exocrine Pancreatic Insufficency was suspected and tested for in 12/08.
A nutritional panel was run at this time as well.
B12 and Folate levels were normal and Exocrine Pancreatic Insufficiency was ruled out as well.

Mikey has had 2 additional ultrasounds as well as an x-ray of his heart since that time. All showed no changes, thankfully.
Protein Losing Enteropathy was suspected subsequently.
Blood tests showed normal levels of albumin and lymphocytes.
Endoscopic biopsies need to be done to rule out Protein Losing Enteropathy,
but Mikey is certainly not a candidate for this at this time.

Our regular vet an IM specialist both felt that, perhaps, Mikey has an inflammatory bowel condition due to a food sensitivity which he had been able to mediate in the past with his own overproduction of cortisol.
However, once the cortisol production was suppressed with the Trilostane, perhaps, the symptoms of Inflammatory Bowel Disease ran amuck and are now creating a Protein Losing Enteropathy or a nutritional absorption problem.
Tylan powder 1/16th tsp sprinkled on food 2x per day was added to his regimen.
They recommended a consultation with a veterinary nutritional specialist and, perhaps, the introduction of a novel protein (hypoallergenic) diet.
Have any of you been down this road?

We met with the nutritional specialist yesterday and she does not necessarily concur with this theory because of the fact that the gas and diarrhea return when the metronidizole is stopped.
Therefore, she believes the problem may be bacterial (such as SIBO) rather than food sensitivty.
A Pro-Biotic treatment approach was recommended and commenced today.
He absolutely hated the taste of this supplement sprinkled on his food and refused to eat his chicken for the first time ever Now What?

I am somewhat enlightened to hear that Dr Oliver has stated that some dogs with excess sex steroids lose weight. Every time I have ever inquired as to the possibility of this phenomenon, I am told that this cannot be!

I truly believe that the Trilostane could be behind this awful weght loss due to it's ability to increase the adrenal sex steroid levels and I cautiously think the time has absolutely come for a change!
I intend to contact Dr Oliver and get his input.
I also wonder if, somehow, the fact that Mikey's aldosterone and andostedidone levels were lowered after the stim could be responsible for the nausea and vomiting he experienced. His androstenedione level was high initially and then went below normal.
Has anyone had any experience with this?
He only vomited once after his 3/30/09 ACTH stim, but, perhaps in November his levels of those hormones went even lower....Just a thought...
I love my boy and I just want to find a way to help him....

Thank you so much for your input!

Love and best wishes..
Dorothy and Mikey
  #9  
Old 04-23-2009, 10:17 AM
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Squirt's Mom Squirt's Mom is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Dorothy,

Just checking in to see how Mickey is doing today.

Weight loss and inappetence are some of the problems I have with Trilo. I haven't really kept a log or anything, but it seems to me that quite a few Trilo pups develop these issues plus shaking in some. We don't use Trilo or Lyso yet, but when Squirt was first diagnosed and I started researching, Trilo was my first choice. But the more I read the less I like it. Since Squirt has been diagnosed as Atypical, Trilo is no longer an option for her, tho.

The flip side is, many pups have done well on Trilo and remained on it for the duration of their life with no or few complications. These pups are each individuals and as such will react like no other! It is good, observant parents like yourself who listen to what their pup is telling them by their behavior that make the difference. I have no doubt that Mickey is in excellent hands and that you will make the best decision for him possible.

I am curious to hear what Dr O has to say about the drop in his hormones. That is interesting.

Let us hear from you when you can,
Hugs,
Leslie and the girls
  #10  
Old 04-23-2009, 04:18 PM
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4Mikeydog 4Mikeydog is offline
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Default Re: Mikey no longer doing well on Trilostane

Hi Leslie,

Thanks so much for your support. Mikey has had issues with shaking as well from Trilostane in the past, but a reduction in dosage seemed to have helped.
I am eagerly awaiting a reply from Dr. Oliver, but I haven't heard from him yet. I hope he writes back.
I know a change in treatment is imminent but I really want to know how to go about making this change with the least amount of risk
I am so worried...But as you all know too well..we must be strong and educated for our babies! They need us to be educated and strong to be their advocates!
Hopefully, we will have a strategy in place soon!

with best wishes,
Dorothy and Mikey
 

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