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Thread: Skippy has passed; 12 y/o Yorkie with likely pituitary tumor (Trilostane)

  1. #141
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Skippy update again - The good news is that his BP is now in the normal 150's and in many respects he is stable - for Skippy. But I continue to see neurological deficits intensifying, e.g., he no longer wags his tail, smiles, can't sit and shake without losing his balance, can't kick his back feet and has given up trying to jump on anything. There are a dozen other tiny changes that I won't bother describing. The local vet thinks his front legs are beginning to buckle. Externally his Cushing's symptoms have not increased although his hair is thin and he is developing new tiny adenomas on his feet and butt. Except, and a big one, for diarrhea, he is tolerating the Cabergoline.

    Next Monday, I guess I will agree to a Stim test if Scott-Moncrieff thinks it is appropriate. Otherwise, I am moving on - to radiation. He will need Prednisone for a month and I want to thoroughly understand the proposed protocol. I also will contact Wisconsin and see if they will look at his MRI and tell me what they would propose and the cost. The research on radiation, various protocols and equipment is slim and mixed. If he survives the radiation and still has Cushing's, which is likely, I do wonder about treating with Vetoryl as reportedly it makes macro tumors grow. I will ask Dr. Scott-Moncrieff but if anyone knows anything or has had experience with this issue, I would appreciate your feedback. So, nine months, and many thousand dollars, I'm grateful and lucky that he has survived this long. And, I know how fortunate I am to be financially able to take the next step; I only hope he survives and radiation gives him his quality of life back, at least for awhile. Thanks again for everyone's kind thoughts and support.
    Skippy's Mom

  2. #142
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Well dang, I'm sorry to hear that the neurological symptoms are increasing.

    Find out if any place has the radiation treatment that only requires two doses (as used by UC Davis) rather than the 10 - 12 that many use. It is much easier on the dog with less risk from what I heard from those that used it at Davis.

    I think worry about treatment for cushings later if necessary. One step at a time.
    Sharlene and the late great diva - Molly muffin (always missed and never forgotten)

  3. #143
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Lengthy trip to Purdue today for Skippy. They did another blood panel, a Stim Test, a Shirmer's tear test (normal) to check his eyes, and I'll drop off a fecal sample tomorrow. I met with the radiologist for nearly an hour. In summary of all issues:

    Blood panel compared to 3/9, most high numbers are higher but they forgot to give me the 3/9 numbers. Here are the highs:

    Total Protein (plasma) 8.5 (Ref. range 6.0 -8.0)
    Hemoglobin 18.8 (Ref. range 12.0 - 18.0)
    Blood Urea Nitrogen 56 (Ref. range 7-32)
    Anion Gap 20.4(Ref. range 9 -18)
    Alkaline Phosphatase 808 (Ref.range 20 -157)
    ALT 288 (Ref. range 3-69)
    GGT 146 (Ref. range 5-16)
    Cholesterol 413 (Ref. range 125 - 301)
    Lipase 6042 (Ref. range 104 -1753)

    BP is 150 after an hour wait to be seen.

    Big concern of the moment is diarrhea. They think the Cabergoline may be causing it so I am stopping it today at least for awhile; they will also look for parasites. Long term use (since April 4) of the Metronidazole can cause neurologic symptoms, something that he already has a boat load of!

    The radiologist said that they have radiated four or five dogs with pituitary tumors. They each survived a year or a little more without new symptoms. One received a second treatment that extended his life by four or five months. Most had dramatic improvement in neurologic symptoms. He thought the highest risk for long term radiation effect was loss of vision because the optic nerve is directly in front of the pituitary He explained the difference between IMRT and Tomotherapy. The latter offers 3D radiation capacity, the former is only 2D but he explained their efforts to offset Purdue's more limited capacity to view the brain. (That, I didn't fully understand but it seems to relate to how they position and "block" the animal on the table.) A second difference is that Tomo has an MRI attached to the radiating machine.) He lamented the lack of research on Cushing's and pituitary tumors and said the reality is that their is a massive lack of research across the whole of veterinary medicine. He said that Docs like him are generalist specialists in that they radiate tumors/cancer wherever they are on an animal's body. They are not researchers per se and there is so little money available for research. Sigh... I am pretty discouraged by this info and I am going to send Skippy's MRI to U of Wisconsin and see if they will offer a consult regarding radiation without seeing him. Purdue proposes to administer three treatments in one week but they have not developed a radiation plan. They could start next week or the following week if we can clear up the diarrhea and I agree to go forward.

    Dr. Scott-Moncrieff explained that Vetoryl does not cause a macro to grow, rather because Vetoryl reduces cortisol levels, it also allows the the tumor to expand. Maybe semantics but here is this: "Because most chemotherapeutic agents have no effect on the pituitary itself, they do not inhibit ACTH secretion, which may actually increase with therapy. This phenomenon, known as Nelson's syndrome, has been well documented in humans with pituitary tumors treated with bilateral adrenalectomy. Nelson's syndrome refers to rapid enlargement of a pituitary mass that occurs after loss of negative feedback from adrenal cortisol production, which has an inhibitory effect on ACTH release. While this phenomenon has been suggested to occur in dogs, studies have shown no correlation between treatment with mitotane and pituitary size or rate of pituitary tumor growth. However, because the exact mechanism behind the development of Nelson's syndrome is not completely understood, the potential for tumor expansion as a result of adrenal corticolysis or decreased cortisol production seems plausible." (http://www.vetfolio.com/neurology/ca...ry-macrotumors)

    While I am very discouraged about Purdue's experience with radiation treatment, I appreciate their honesty and liked the radiologist. Ultimately I guess it will be a question of trade offs. Purdue's experience with Skippy in general versus their not so great radiation outcomes with pituitary tumors. Although, I don't know any details regarding the other dogs and there could be other extenuating factors. And, I don't know the radiation outcomes for any other vet hospitals either. The reported research consensus seems to be nearly two years. But hey, I don't even know if he will survive radiation.

    Thanks everyone for enduring my too lengthy reports and diatribes; this is so exhausting. Another time I will write about Purdue faculty's concern about their lack of bereavement and end of life counseling for their clients; it was an extended and troubling conversation. I would appreciate any feedback regarding radiology programs and will again search this site for other's experiences.
    Skippy's Mom

  4. #144
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Hi Carole,

    You are certainly leaving no stone unturned in what has got to be an exhausting process for you. You are doing a super job of researching these treatment options for Skippy!

    Just to expand the discussion a bit further re: Nelson's Syndrome, the 2008 article you cited said that no correlation had yet been established at that time with treatment by mitotane (Lysodren), even though it seemed reasonable that the potential for that treatment effect does exist. However, here's a 2009 article that does offer credibility to a linkage between trilostane and this effect:

    http://www.ncbi.nlm.nih.gov/pubmed/19041802

    Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis
    Domest Anim Endocrinol. 2009 Jan;36(1):32-44. Epub 2008 Nov 11.
    Teshima T, Hara Y, Takekoshi S, Nezu Y, Harada Y, Yogo T, Teramoto A, Osamura RY, Tagawa M.
    Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan

    Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported. However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect.

    The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary-adrenal axis in clinically normal dogs.

    Dogs were administered 5mg/kg trilostane twice a day every day for 8 weeks (n=8) or 16 weeks (n=3). After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably.

    As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged. After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals.

    In addition, histological examinations revealed bilateral adrenal cortical hyperplasia. Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs.

    These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs. These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease.
    Once again, it would be great if additional research could further illuminate this effect, but I don't know whether any more exists. Anyway, just wanted to share these study results with you.

    I really wish I could offer some words of wisdom to you re: the path forward. Over a decade ago when we were considering radiation for our Cushpup, our IMS also said that he'd seen dramatic improvement in neurological symptoms that lasted for about a year, as well. However, a huge barrier for us was not wanting to subject our boy to the dozen general anesthetics that would have been required at that time. I'm an anesthesiologist's daughter, so I don't take those risks lightly . Had we been able to consider a protocol involving fewer treatments, our decision might have been different. But I just could not see putting him through that many procedures when there was no way for him to understand how and why it was happening. Plus, his traditional Cushing's symptoms were quite disabling, and we had no guarantee that they would abate post-treatment.

    My intention in telling you all this is not designed to discourage you from moving forward if you decide that is what is in Skippy's best interest. But rather to let you know that I surely realize it's not an easy decision to make. Please continue to update us as you gather more info, and as you weigh the pros and cons.

    Marianne

  5. #145
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Carole - continued wishes for good luck and outcomes with Skippy's treatment, whatever you decide is the path forward.

    It does seem that a lack of research and funding is affecting the way decisions are made and that is concerning with the number of Cushing's dogs out there ... I do hope this will change over time.

    One thing you mentioned was the Purdue faculty's disappointment with the end of life and bereavement care for their clients .. I would like to hear more about this. I could have used some clear guidance and support while Mojo experienced his last few weeks of life and decline. Feel free to send me a private message for more focused convo ...

    Please know that I think of you often and pray for you and Skippy. I know there is a good answer out there for you and I am in awe of your dedication to informed decision making. It is truly inspiring and I know that so many will be helped simply by reading your reports. Sharing your research is so important and thank you for doing so.

  6. #146
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Carole, you are a wonderful mom to Skippy and your dedication and expertise in navigating through the complicated medical terms is amazing. Trying to keep it all straight in your head plus dealing with the emotional side of all of this must be exhausting. Please take care of yourself too! I also am interested in the end of life & bereavement care info, when you have time. Makes me wonder if there was something else I could have done for Whiskey in these last months. Again, please take care. Hugs to you and sweet boy Skippy.
    Annie

  7. #147
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    I think all around that more research is needed into cushings, medications, cause and effect, macro, adrenal. There are tons and tons of areas that need more research and just not enough research dollars to go around.

    You are doing an excellent job Carole and probably know as much and/or more about macros now than most people will ever want to know.
    Sharlene and the late great diva - Molly muffin (always missed and never forgotten)

  8. #148
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Please allow me to move past all of the other issues that I have raised on my thread and you all have responded to so thoughtfully. I will return to them. Right now I am furious and really don't know what to do next. Yesterday I sent a carefully worded email to Wisconsin's head radiologist providing Skippy's brief history, medical situation and MRI. I stated clearly that I had met with Purdue radiology and that their radiologist stated that he felt that Purdue could compensate for the limitations in their radiation equipment although I didn't understand how. I inquired about and requested that Wisconsin consider him for their Tomotherapy, a version of cyber knife. I get an email back just now, at 10pm saying "You are in good hands with the radiation oncology team at Purdue...Their equipment is very similar to our TomoTherapy system. Their system can treat Skippy's tumor and spare normal tissue. Skippy will get excellent care at Purdue."

    Is this a freakin secret club of professionals who choose not to step on one another's toes out of professional courtesy? Who cares who gets my money; I just want Skippy to have the best shot! I am beyond livid. I live on the east coast. Should I explore vet hospitals out there? Penn, NYC or should I just surrender and put him down?
    Skippy's Mom

  9. #149
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Carole, I surely understand your frustration. However, I am guessing the Wisconsin team's email may relect their honest opinion. Having worked in a hospital setting for several years, I acknowledge having witnessed professional courtesy "after the fact" (docs not wanting to be openly critical of previous actions taken by others). However, when it comes to promoting their own abilities or treatment advantages in advance, they are seldom shy . So for whatever reason, they may not believe their own system offers enough advantages in Skippy's situation to make the travel worth it.

    From what you have told us about Purdue, I guess my greatest worry would be the fact that they have performed the procedure on only 4-5 dogs. That seems very strange to me that a university vet school would have treated so few macros over the course of years. Across the board with any type of procedure, it is generally thought that programs that do higher volumes will be more adept. I think Purdue's results, however, pretty accurately reflect the experience we've seen here with dogs who have been treated via radiation, regardless of modality. One year of symptom-free life seems to be the norm, with longer time being the frosting on the cake.

    As I wrote earlier, one big concern I have had about traditional radiation programs is the number of procedures/anesthetics required. But is Purdue capable of completing the treatment in only three sessions, regardless of their less sophisticated equipment?

    I know you have a lot to think over, and for your own peace of mind, you may still want to contact some additional programs that offer the cutting-edge technology, in order to get their opinions as well. I'm surely sorry there are so many hard decisions involved!

    Marianne

  10. #150
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    Default Re: Skippy, 12 y/o Yorkie with likely pituitary tumor (Trilostane)

    Hi Marianne,
    Thank you for responding to my dilemma. Even after sleep I am still shaking with anger. I am deeply concerned that Purdue has only treated four or five dogs. I am concerned about their lack of experience with radiating macros and I am concerned about their equipment. I nicely ask Wisconsin all of those questions and got the blow off response. In answer to your question regarding number of treatments, yes, Purdue has said from the outset that he would receive three treatments, a Monday, Wednesday, Friday. In April I met with a group of Purdue folk, surgeon, radiologist and internal medicine and a bevy of students. I ask about short and long term radiation effects with the three treatment approach there. A different radiologist acknowledged that yes, three treatments with a larger dose of radiation (with their equipment) increases the probability of long term radiation effects, i.e., dead dog walking. The first radiologist also said the median survival after treatment at Purdue is TWO years, not one. (I think she meant for all radiated dogs, not just dogs with macro tumors, but I was too dumb or too in shock to ask the question properly.)

    You likely are correct that the outcomes of radiation with Tomo or Cyberknife are not necessarily better for many dogs, especially for those whose macros are large with severe neurologic symptoms. All the more reason that one might want a program with the best equipment and most experience. Lack of experience was why I
    wouldn't consider surgery although Purdue was willing to pitch in big bucks for Skippy to launch their program.

    I tried to draft a response to Wisconsin last night but I know in reality I need not bother. I also believe that the private hospitals in NYC, PA and Virginia are going to charge a larger fortune than I have remaining to invest in this endeavor. Colorado State has the most experience and high end equipment but I don't see how that is feasible. But, I don't know until I try and thanks again for your feedback; it really is helpful.
    Skippy's Mom

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