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Old 08-20-2013, 09:09 PM
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Post New Cushings Case (12.5 y/o Boston Terrier)

Hi everyone. My name is Jen and I have a 12 1/2 year old Boston Terrier named Jigsaw. She is my love (as I'm sure you all feel the same way about you kids, thats why we are meeting here). Here is her story, and please any input is openly welcome. Let me apologize now for it is a lengthy story.

Last January she developed what looked like vasculitis bilaterally on her ears, crusty, flaky, and would bleed. They were affected identically. We did a full blood workup and everything looked good, only her BUN was a a bit under the low normals. Instead of doing a biopsy, we decided to treat her with Tacrolimus topically first and monitor response. I thought I saw a little improvement after a month, but decided to add in pentoxifylline as well. After adding this I did see noticeable improvement, but never completely resolved. I realize that not all vasculitis cases completely resolve so at that time I was ok with what it looked like.

In late April, I noticed that she started drinking a little more and asking to go out as well. I continued to monitor and was increasingly getting concerned as time went on about diabetes, kidney, or cushings.

At the beginning of May, I went to my vet and expressed my concerns, and we did a first morning urinalysis and she had some protein, no ketones, with a specific gravity of 1.012. Oh crap. Stopped the Pentoxifylline. So diabetes is ruled out, but now kidney or Cushings. The next 3 mornings we did specific gravities and all 1.012.

Retrospectively, I was thinking about her haircoat... (she has always had hairloss due to a worked up diagnosis of Adrenal Gland Sex Hormone Imbalance when she was 9 months old) and realized that her haircoat had become brittle, losing more hair on her thighs, and she was still brown in Spring, I live in Oregon we don't see the sun until July (of course she is a sun worshiper so she is always brown in the summer and then black in the winter).

Now I was sure she was Cushnoid, right? We did bloodwork again, BUN again just under low normal, Glucose of course was normal, ALT, Alk Phos were NORMAL. What? How can that be? I was sure she was cushnoid. She did not have the classic signs of a pot belly, but.... By the time we did bloodwork, finally got the results interpreted, and spoke to the vet (after 4 days), she was just starting to show some muscle weakness in her hindquarters, a little bit confused, her water consumption really amped up, along with trips outside almost on the hour, oh and the stance... shifting her weight to the front due to her weakness in the hindquarters, certainly she is cushnoid. My vet said, I don't know, her bloodwork looks good, you need to go to the internist.

The internist had an opening 2 weeks later, and by that time her symptoms had really worsened. She couldn't jump up on the couch, she was wobbly, seemed like senility had really set in. We went over her history, and she too thought she was cushnoid. Good but not good. She said even though she did not have the classic pot belly and the elevated ALT and Alk Phos, 5% of patients will not. We did a LDD and sure enough, we confirmed Cushings. I felt ok about the diagnosis because I knew that with medication, she could have a good quality of life. She had been on Lysodren (mitotane) for 4 1/2 years with the Sex Hormone Imbalance with it never helping her hair regrowth, so I was advised to discontinue it slowly and monitor response. No change, so she has been off it for 7 years. For the Cushings, the internist advised me to try Trilostane, it being a better drug of choice, and of course I'm on board! Here we go!

She started the Trilostane 8mg bid, by the 10th day that evening, she started kinda a grunt, reverse sneezing thing, with slightly open mouth breathing. Odd, had never heard of this being a side effect, but regardless I was 2 hours away from Emergency and 1:30am so I gave her Pred, bummer because she was suppose to have her stim that morning. Two hours after giving her the Pred the symptoms went away, didn't matter though she was going to be at the internist front steps first thing that morning. Of course she showed no signs of the breathing issue, and I think they thought I was overreacting and maybe I was just seeing reverse sneezing or something...uh nope! Of course I had to wait another week for the stim and was advised to restart the Trilostane, so I did. Everything was going fine for the first 4 days and then the breathing thing started again along with hard sneezing, clear liquid drips from her left nostril, trembling, and lethargy. She was of course still eating! They asked me to videotape it, so I did. They were thinking maybe with her cortisol level decreasing, it was maybe allergies getting stirred up, maybe a tooth root abscess, a foreign body, tumor maybe.... I was advised to continue the Trilostane. I relunctantly continued with her symptoms worsening, and then her stim test. After seeing her for the stim test, the internist came out and added another possibility for the nose issue...aspergillis. Her thought was because it was only 1 nostril, and her lungs and heart sounded good. The slightly open mouth breathing was because she couldn't breathe out her nose. The other possibilities are still there, but she just added that to the list.

So her stim came back 2.2. I was advised to decrease to 6.4mg bid due to the results being on the low side of normal. I did but she continued to worsen. Two days later, I talked to the tech, and said I have to stop, she is miserable. Her drainage is a bit green now. The tech said continue until I get an answer from the doctor, I just couldn't!!! I stopped it that night. Thankfully the next day, another tech called and said discontinue for 3-4 days, monitor, and then restart the Trilostane at 4.8mg bid. After the discontinuation she amazingly got back to her old self a little bit each day. I couldn't believe the turnaround in her. By day 2 off of the meds, she had no nasal drainage, no lethargy, no sneezing, she was sunbathing again, waking me in the morning by standing on my chest and stretching, being all lovey. Thank god my girlie is back. I emailed the internist and explained the miraculous change in her and explained how reluctant I was at starting her back at 4.8mg, so she said try 3.2mg bid instead and if the symptoms return decrease to 1.6mg bid. I just couldn't bring myself to start at 3.2mg, I thought I'll start her low at 1.6mg and then if no symptoms, I'll increase to the recommended 3.2mg, etc.

I started her on the 1.6mg and the first 11 days, she was doing great. She was acting totally normal with no symptoms, until day 12. She started slowly with the nasal drip, then the green gunk, the sneezing, and now lethargy again. So far, no trembling. She had a stim today and hoping within the next 1/2 hour to have the results. I have decided to discontinue the Trilostane and monitor her response until she is back to her normal self again. I haven't spoken to the internist yet, but does anyone have any experience in using Trilostane on such a low dose? And has anyone ever dosed every other day?

I do realize that the nasal thing is not a side effect directly linked to the Trilostane, but indirectly causing this to occur. I suspect a tumor, I pray I'm wrong, but whatever it is, it seems to like the over abundance of corticosteroids she produces when off the Trilostane.

Oh and back to the Vasculitis with her ears... I don't think so! Since being treated with the Trilostane, her ears have improved with no Pentoxifylline and every other day application of Tacrolimus. So obviously she had calcinosis cutis with her ears not vasculitis. Hindsight is always 20/20, but if I had biopsied the ear, we would have known in January what the ears were, and then been able to look directly into the Cushings. With the Trilostane the water consumption and urination is back to normal as well, and her haircoat is already becoming soft again. I need to find a balance, and if anyone has suggestions or comments, please do.

As far as working up the nose issue, I don't mind spending the money, but with her being depressed and not herself, I can't even imagine putting her under anesthetic for a CT and rhinoscopy. What do you all think?

Thanks for the feedback!
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Old 08-20-2013, 10:32 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Hi Jen and welcome to you and Jigsaw,

Wow, it seems Jigsaw really is a jigsaw. I am so sorry for everything you and he are going through. I wish I could help, but I am sure others will stop by to welcome you and maybe be able to offer some help.

One of our admins just had her pup go through some nasal surgery, she may have some insights or idea's

http://www.k9cushings.com/forum/showthread.php?t=5603
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Old 08-20-2013, 10:35 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Hello and welcome to the forum Jen and Jigsaw. What a cute name.

Wow, what a journey you have had. Do you by any chance happen to have the result of that LDDS test that you had done to diagnose the cushings? Also the ACTH tests that have been done. Is her BUN still low?

Okay, first I'll say I haven't heard of this symptom, but many of admins and mods have been involved with cushings for many, many years so they might have an heard/seen/read something. This is very baffeling, but the main thing to remember is that ever dog is different and responds differently.
Have you thought about going back to lysodren instead of the trilostane? I don't see you mentioning it but have you had an ultrasound done? Was an ACTH done prior to starting trilostane? I'm curious about the baseline readings on her cortisol, or if perhaps her cortisol wasn't risen and her sex hormones were. (in which case, it would be called atypical and lysodren is the usual treatment) To find that out, you'd see if her cortisol while off trilostane is risen at all and if not, then send a panel to UofTenn. They are the only place that does that specific test that we know of.

I do understand the worry about the tumor, I am guessing that is the thought due to the disorientation that you mention.

One other thing that can also be done, is to call Dechra (the makers of vetroyl) and tell them about this and see what they have to say. They will give you a case number that you can give to your vet and internist and will consult with them and talk to you. Now aren't you glad you live in the states as this is the only place I know of that offers that service. Many of our members have contacted Dechra directly and they have generally been Very helpful. I think this would definitely warrant a call as it is so unusual and seems to be related to either, the trilostane, or the cortisol being lowered. That is a question that needs to be determined for sure. Dechra 913-327-0015 I know they have a Toll Free number, I don't see it right now though.

Some of the others will be by to soon to welcome you and to pass on their thoughts.
I'm very glad you found us, and we'll be right here, all the way.
I do want to say, you have done awesome, on what has been a very long year. Hang in there.

Sharlene and Molly Muffin
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Not currently being treated for cushings, but monitoring liver values.
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Old 08-20-2013, 10:44 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

I've been here since before trilostane was legally available in the US and I honestly don't ever ever remember having that kind of symptom/reaction to trilo. As I read your story I honestly thought you were going to end it with "and we found out my dog doesn't even have cushings".

Watch the dosing as we see it tends to have a cumulative effect and alot of dogs have to lower doses over time. The cortisol level is pretty low now. Lastly I think calling Dechra re your experience is a fantastic idea. We have a lot of members who have had success in talking to their vets... very helpful.

Glad you found us. Kim
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Old 08-21-2013, 07:45 AM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Hi Jen and welcome to you and Jigsaw!

I love the name!

You did a great job in providing the current history but there is quite a bit missing.

Why was she on Lysodren 7 years ago? Do you have the testing from then and would you post the results of all those here?

Between the time of stopping the Lyso and the current issues, how was she?

I am assuming Jigsaw was tested by the Uni. of TN to determine the sex hormones, intermediate hormones, were out of balance? If so, Trilo is not recommended for these pups by UTK; they recommend Lysodren for these pups tho there have been these pups on Trilo. Would you mind posting these test results from UTK?

Has she had an abdominal ultrasound? If not, I would have that done asap. It can go a long way toward confirming Cushing's as well as getting a look at other organs.

If I were you, I would stop the Trilo. I am not convinced Jigsaw has Cushing's. Has her thyroid been checked lately? Has she been checked for diabetes lately? Two conditions that mimic Cushing's and can cause false-positives on the testing.

Non-adrenal illnesses are notorious for causing false-positives on the LDDS. Was an ACTH done?

Have her ears been tested by a derm vet? IF this is calcinosis cutis, they will be able to confirm. That diagnosis would also go a long way toward confirming Cushing's as CC is pretty much a cush condition.

One thing I feel the need to mention even tho I don't want to - Trilostane has been shown to cause the cushing's pituitary tumors to grow, leading to a macro. Like others, I have never heard of the reactions you are seeing to Trilo or a macro but each pup is a unique biological entity so those reactions would be possible I suppose.

Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis. (causes growth of macros)
http://www.ncbi.nlm.nih.gov/pubmed/19041802

A MRI could confirm a macro if this is deemed a possibility. Cush pups with the brachycephalic skull, what I call the smush-face profile like Bostons, Boxers, etc., are more prone to macros for some reason. Sorry to add to your worries.

I'm glad you found us and look forward to following your story. You have done a great job with Jigsaw and she is very lucky to have you as a mom.

Hugs,
Leslie and the gang
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Old 08-21-2013, 03:32 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Thanks! Truly the support is terrific and greatly appreciated.

Jen & Jigsaw
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Old 08-21-2013, 05:07 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Wow, you all have so many good questions. I'll try to answer them in some sort of order.

October 2001 - (7 months) Spayed

January 2002 - (10 months) Beginning of hair loss, monitor

February 2002 - (11 months) Symmetrical hair loss on ventral trunk, medial extremities, and ventral neck
and chest, non pruritic, Blood work normal

March 2002 - (1 year)Diagnosed with Adrenal Sex Hormone Imbalance by Boarded Vet Dermatologist

University of Tenn Blood Results
Cortisol Base=23.9 Range=2.1-58.8
Post=153.9/2hr=112 Range=65.0-174.6
Androstenedione Base=9.9 Range=0.1-5.7
Post=63.9/2hr=19.8 Range=2.7-39.7
Estradiol Base=62.1 Range=30.8-69.9
Post=55.1/2hr=54.9 Range=27.9-69.2
Progesterone Base=0.34 Range=0.01-0.49
Post=2.65/2hr=1.43 Range=0.10-1.50
17 OH Preogest Base=0.54 Range=0.01-0.77
Post=5.73/2hr=3.37 Range=0.40-1.62
Testosterone Base=0.02 Range=0.01-0.32
Post=0.03/2hr=0.03 Range=0.02-0.45
Recommendation from UTenn due to her age, rec ultrasound to rule out adrenal tumor or ovarian stump.

March 2002 - Ultrasound Normal

March 2002 - Started Melatonin 3mg tid & Pentoxifylline 60mg tid No Change

April 2002 - Started Mitotane (Lysodren) with lots of Stim Tests over the next many months to finally get
her dose range 55-65mg sid. She never had any adverse effects from the medication.
Dosages were only changed due to the results of the Stim Tests.

*UTenn Blood work done yearly til 2005 w/ Stim Tests.

June 2006 - (5 years+) New Boarded Vet Dermatologist advised that if no improvement over all these
years, slowly decrease the Mitotane over the next several months and monitor response. If no
changes in hair coat, etc, then stop medication forever.

August 2006 - Stopped Mitotane with no side effects noted.

*Historically Jigsaw has always had a BUN of 5-8 Normal=7-27

August 2012 - Bloodwork/Thyroid Normal Ranges

January 2013 - Bloodwork/Thyroid Normal Ranges

June 20, 2013 - Bloodwork/Thyroid Normal Ranges

June 28, 2013 - Bloodwork
T4=0.9 Range=1.0-4.0
ALT=127 Range=5-107
GGT=21 Range=0-14

June 28, 2013 - Ultrasound Normal

July 3, 2013 - Low Dose Dex
Resting=1.0 Post 4 hour=1.6
Chest Films - Clear
Urinalysis Culture - Clear

July 12, 2013 - Started Trilostane 8mg bid

July 21, 2013 - UR issues

July 22, 2013 - Gave Pred 5mg, symptoms disappeared after 2 hours, no Trilostane that morning, restarted
8mg bid that night

July 24-25, 2013 UR issues again, advised to continue same dose until stim on July 29

July 29, 2013 ACTH Stim Test 2.2 (Trilostane 8mg bid x 1 week)

I think from there you can pick up the rest from my OTHER long story.

August 20, 2013 ACTH Stim 4.8 (Trilostane 1.6mg bid x 13 days) Bloodwork - Normal Ranges

Talked to a new Internist today, and we (together) decided to discontinue the Trilostane until Friday and see how she is feeling. If she is feeling totally back to normal, then she wants to restart at 1.6mg sid, if not wait through the weekend and check back in with her. We did talk about moving to Mitotane, but I felt she wanted to give the Trilostane another chance.... I kinda feel at this point, why not try Mitotane? I know she tolerated it last time, knowing that it was many years ago and her body has changed.... but maybe that is a better choice. Have any thoughts?

Okay I think that concludes the preface and body of my story, now I'll I need is that "they lived happily ever after".

Thank you again for the input and support. It truly means the world to me that I am not alone and you all understand my feelings.

Thanks again,

Jen & Jigsaw

Last edited by nvmybostons; 08-21-2013 at 05:20 PM. Reason: Easier to read
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Old 08-21-2013, 05:37 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Well, one thing I see right off the bat is the initial treatment for the Atypical is not correct. It takes the combination of melatonin and lignans to affect the intermediate hormones. One or the other alone will not work. So I'm not in the least bit surprised the treatment prescribed didn't work even with the addition of the Lysodren. When the Lyso was started was she loaded or was she put on a maintenance schedule where she got the med 2-4 days a week? The melatonin and lignans can take 4 months or so to work so patience is required for this form of Cushing's. After that length of time, if the intermediates are still elevated, then the Lyso is added as a maintenance only.

Quote:
June 28, 2013 - Ultrasound Normal
Were both adrenal glands seen and both were normal?

Quote:
July 3, 2013 - Low Dose Dex
Resting=1.0 Post 4 hour=1.6
The LDDS has three numbers; there should be another result at the 8 hour mark. And would you mind posting what the lab says concerning interpreting the results? Most are the same but some do differ.

If you want to switch back to Lysodren (Mitotane), and that would be my choice with the intermediates already elevated, you will need a wash out period between the two drugs of 30 days. Meantime, I would start her back on the melatonin and add the lignans asap. You can wait several months before revisiting the Lyso while you wait to see what effect this combo is having.

Hugs,
Leslie and the gang

http://www.vet.utk.edu/diagnostic/en...ings201107.pdf
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"Remember these moments always, but do not ignore the sad times, either. Memory is the greatest of gifts."

Spoken by Aditu, a Sithi (an Elf)
from "To Green Angel Tower II"
by Tad Williams
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Old 08-21-2013, 05:59 PM
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Question Re: New Cushings Case (12.5 y/o Boston Terrier)

Excuse my ignorance, but what are lignans?

When the Lysodren was started it was at a higher dose 125mg sid. She never was put on a 2-4 times a week treatment, it was always sid.

So I understand about the 4 months for it to work for the Atypical Cushings, but now she is Typical Cushnoid, right?

In her last ultrasound, yes both adrenal were seen. I was told normal, although, they said the reference they give is the same for a 100lb dog and a 10lb dog, seems a bit odd to me, but....

I stayed for the LDD and I dont recall being there for 8 hours, I thought it was a 4 hour LDD.

So you would still rec. starting her on the melatonin and lingnans even though she now has typical Cushings (not just her haircoat)?
Her typical Cushnoid symptoms were PU/PD, muscle weakness in her hindquarters, confusion, brittle hair coat, suspected CC on her ears, ravenous, etc (Unsure if I made that all clear in my first post)

Are you a vet? I've worked in veterinary medicine since 1986, general and specialty practice, and always learning more and more. I just wish it didn't have to be first had experience, ugh!

Thanks again,

Jen
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Old 08-21-2013, 08:51 PM
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Default Re: New Cushings Case (12.5 y/o Boston Terrier)

Hi Jen, no we aren't vets. Most of our admins though have years and years of experience with cushings. That comes from having a couple thousands members, over 300 of which are active at any given time it seems. Which is rather sad, to think of all them going through the same issues. Anyway, sorry, I got off track for a moment in my thoughts.

Dr. Oliver, from UofTenn, still the only place that does testing for Atypical Cushings (elevated sex hormones), was a great friend to k9cushings prior to his passing and his recommended treatment is still the recommendation to this day. He helped many members among them Leslie.

His passing was a great loss to the canine cushings community and to this forum.
What Leslie said is taken directly from his research papers and from her communication with him. It is also what is considered the standard for Atypical treatment and this is a combination of melatonin and lignans, with lysodren being added if no improvement is seen. Leslie or one of the others can tell you exactly how the lysodren is added.
I haven't had any personal experience with the treatment, but I am aware of Dr. Oliver's research.

I don't know about now with a cushings diagnosis, just that for Atypical that is the recommendation. I'm sure some of the others will pop in with their thoughts.

I can say that yes, an LDDS test will have a base draw, then the injection, then a 4 hour and an 8 hour draw. You are basically looking to see if and how much they will suppress at each draw 4 and 8. Some will suppress at 4 hour and then escape by the 8 hour. Some vets use the suppression rates at the different mark to try to determine pituitary vs adrenal cushings. I've had 4 LDDS tests for my dog in the last couple years. It is given the same the world over, so no different in Canada, Brazil or the US.

The ACTH test on the other hand takes a base draw, gives an injection and then an hour later takes a draw to see how much cortisol is dumped into the body from the adrenal glands. This cortisol is normally sitting in reserve in the adrenal glands and dumped after the injection. In some countries, if a compounded agent is used, then you will have two draws rather than one and they are about at the 1 hr and 2 hr mark. Canada uses this method for ACTH testing in most areas.

okay, wow, that was a lot of info for a simple question eh.

I agree, it doesn't matter how long you are in this life, there is always something new just around the corner to be discovered, learned, enjoyed and puzzled by. Part of that life is a mystery thing that seems to be never ending. I have to say I have learned so much on this forum about cushings. I knew Nothing it seems when I walked in the door. Yet, here we all are today, still trying to figure so much out. Cushings is horribly hard it seem to get a firm handle on. (We're still trying with my dog, and we just take it day by day, month by month)
That and a good colorist for the gray hair it gives me. LOL

Gosh, I don't know if that helped, or hindered, sorry, I did sort of prattle on for a bit.
Sharlene and Molly Muffin
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Not currently being treated for cushings, but monitoring liver values.
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