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Thread: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

  1. #11
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    Default Re: Before prescribing Trilostane....

    Me again, with one more thought.

    Perhaps another situation where dogs might be tested while actively being treated is when an adrenal tumor is present? In an email, I asked Dr. O about using the UTK panel for "monitoring" rather than strictly diagnostic purposes, and this is what he said:

    I shouldn't totally dismiss the idea, since very few veterinarians are doing this yet. With experience, it may turn out to be very useful. I just know that trilostane increases the intermediates, and it makes it difficult to know if it's due to disease or the drug. It probably would be of value to do it with ADH maybe one time, just to see what's going on with the ADH condition. Trilostane has mostly been used for PDH, as I understand it.
    So it seems as though there may always be situations where an individual vet thinks that UTK testing may be of special value in the treatment of a specific dog.

    Marianne

  2. #12
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    Marianne, this is probably no surprise to you but I can't remember any members who have reported return of symptoms, despite twice daily dosing and a current acth stim showing effective control of cortisol. I am aware that Dr. Oliver reports that some dogs do fine initially on Trilostane but may have problems down the road because of increasing intermediate hormones but where is the documentation by UTK or anybody else for that matter? You would think that with the UK and a number of European countries that have a lot more history with Trilostane and who have conducted a number of studies on the drug, there would be something out there mentioning this phenomenon.

    On the flip side, however, there is research showing that the majority of dogs treated with Trilostane, particularly for Alopecia X, demonstrated improvement despite no change, and in some cases, an actual increase in 17OHP concentration. So where do you go with that bit of information? I went back to Lulu's medical records to see if she fit the pattern.

    Some folks may recall that Lulu started treatment with Lysodren but I switched her to Trilostane about a year later after my pharmacist said it had less side effects. All was well and good until her new IM and I discovered that a UTK panel was part of testing done for her original diagosis two years earlier, which reflected elevated intermediates. We thought the Trilostane could have been the reason why she never regained her coat. After a 30 day washout we did another UTK panel which showed intermediates were now off the chart in comparison to the original.

    08/22/08 Post ACTH:
    Cortisol = 202.3 (66.7 - 174.8 ng/ml)
    Androstenedione = >100 (3.8 - 42.1 ng/ml)
    Estradiol = 84.8 (31.8 - 63.1 pg/ml)
    Progesterone = 7.9 (.33 - 4.33 ng/ml)
    17 OH Progresterone >25 (.68 - 4.44 ng/ml)
    Aldosterone 507.1 (72.9 - 398.5 pg/ml)

    You would think that with those huge elevations, she would have had raging symptoms but she was totally asymptomatic for three months after the UTK panel. We started Lysodren at the end of November, 2008 after return of symptoms were apparent and an acth stim showed post cortisol at 25.2 ug/dl. So for Lulu it wasn't the intermediates that were driving the symptoms, it was the cortisol.

    Lulu's baldness and Jojo's continued PU/PD, plus their breed being predisposed to hormonal imbalances, have been huge motivating factors in my drive to know more about elevated sex hormones. I was convinced that Trilostane was responsible for both of their unresolved symptoms but they've been on Lysodren for a very long time and it too has failed to resolve Lulu's coat issues or Jojo's PU/PD. For clarification purposes, Jojo did not respond to desmopressin eye drops on two different occasions so central diabetes insipidus was ruled out.

    Lulu was on melatonin and lignans for over a year and her skin and coat were no better. The only improvement we've ever achieved with her skin was after I put her on a great fish oil I got from the vet. She's a couch potato anyway but with the melatonin, she was comatose most days. Lulu's IM and I discussed the efficacy of meltatonin and lignans and we decided to discontinue treatment with these supplements. Since then, Lulu has become more alert, more active and a lot more affectionate.

    Without credible research, the effects of Trilostane on intermediate hormones will remain ill-defined, which means I can only rely on what I read and my own experience with Lulu and Jojo, including treatment with Trilostane and Lysodren. Based on that, I am no longer convinced, beyond a shadow of a doubt, that long term treatment with Trilostane is an imminent problem.

  3. #13
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    Hi and welcome from Corky and me.

    Corky had the stim test and the LDDS tests done, along with ultrasounds, which showed that he has adrenal Cushings. He has a tumor on his right adrenal gland. Corky is being treated with Trilo. After 10 days of being on Trilo, he had the full adrenal panel done.

    Due to anxiety issues that Corky is currently having, his IMS did the full adrenal panel, in addition to a complete blood work-up, and another U/S. I am now waiting for the results of the adrenal panel. Dr. Oliver did e-mail be back regarding the intermediate hormones being elevated because of his being treated with Trilo. Since he had the adrenal panel done before after being on Trilo, at least I will be able to make a comparison between the two tests.

    I know that this can all be very confusing. Hopefully, after there have been more studies done on the effects of Trilo, we will all be able to get clearer answers to our questions.

    Terri

  4. #14
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    Default Re: Before prescribing Trilostane....

    Quote Originally Posted by labblab View Post
    Me again, with one more thought.

    Perhaps another situation where dogs might be tested while actively being treated is when an adrenal tumor is present? In an email, I asked Dr. O about using the UTK panel for "monitoring" rather than strictly diagnostic purposes, and this is what he said:

    I shouldn't totally dismiss the idea, since very few veterinarians are doing this yet. With experience, it may turn out to be very useful. I just know that trilostane increases the intermediates, and it makes it difficult to know if it's due to disease or the drug. It probably would be of value to do it with ADH maybe one time, just to see what's going on with the ADH condition. Trilostane has mostly been used for PDH, as I understand it.

    So it seems as though there may always be situations where an individual vet thinks that UTK testing may be of special value in the treatment of a specific dog.

    Marianne
    I totally agree but I think a before and after UTK panels of an ADH dog on Trilostane would be more valuable. The likelihood of elevated intermediates with an adrenal tumor is great and with Trilostane being known to enlarge the adrenals and elevate intermediates, I'd be really curious to see if the intermediates are markedly higher after treating and if so, did symptoms correlate with these increases. Do we have any volunteers? Is that Terri I see with her hand up?

  5. #15
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    LOL! I volunteer.

    I don't know how much of a difference there will be, since Corky was only on Trilo 10 days before he had the first adrenal panel done. I know that his adrenal gland had increased in size before, but his U/S last week did show that there was no increase in size of the right adrenal gland. There was actually a slight decrease in size. When he had the U/S done last month, the adrenal gland was 1.9x3.3. This time is was 2x3.
    Last edited by littleone1; 03-26-2010 at 06:11 AM.
    Love and hugs,

    Terri and (Angel) Corky

  6. #16
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    I thought I would "bump up" this thread since there are so many active discussions going on right now re: trilostane/Atypical Cushing's/the UTK adrenal panel.

    For anyone who is considering requesting the UTK panel for their dog at any point in their treatment, I strongly encourage you or your vet to first correspond with Dr. Oliver at UTK in advance. Thus far, Dr. Oliver has always been very willing to talk directly to pet owners in addition to vets. There can be so many variables involved in each dog's situation. Dr. Oliver can best tell you whether the UTK panel might be helpful to you, and if so, what the best timing would be (e.g., must the trilostane treatment be suspended, and if so, for how long a time).

    Here's a link providing general contact information for Dr. Oliver:

    http://www.vet.utk.edu/faculty/oliver.php

    Dr. Oliver's email address is: joliver@utk.edu

    Marianne

  7. #17
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    Variability of estradiol concentration in normal dogs

    Abstract

    Estradiol concentrations are evaluated in canine serum as part of an adrenal panel used to diagnose atypical Cushing’s syndrome and other endocrine abnormalities. Estradiol concentrations are often elevated in dogs without clinical signs of hyperestrogenism, and the significance of this elevation is unknown. The purpose of this study was to estimate the variation in estradiol concentrations in normal dogs. Ten neutered male and female dogs were enrolled in the study. Blood was collected from each dog at 2 h intervals, four times during a given day. This was repeated approximately 1 (week 2) and 5 weeks later (week 6). There was no attempt for a given dog to be started at the exact time or day each week. Results showed that estradiol concentrations ranged from 44.6 to 120.3 pg/mL with a mean of 70.4 pg/mL, which is greater than the upper limit of normal for our laboratory (69 pg/mL). The mean difference between the highest and lowest concentrations for each dog was 28.8 pg/mL, with a range of 12.5–53.5 pg/mL. Mean estradiol concentrations from week 6 (63.2 pg/mL) were significantly lower than those from week 1 (71.4 pg/mL; P = 0.015) and week 2 (76.5 pg/mL; P = 0.0004). These data show a wide range of variability in estradiol concentration both within and between dogs and that these measurements often exceed the normal ranges established by the laboratory. Therefore, diagnosis of hyperestrogenism or atypical Cushing’s syndrome based on increased estradiol concentrations should require compatible clinical presentation of hyperestrogenism together with elevated serum estradiol.
    http://onlinelibrary.wiley.com/doi/1...896.x/abstract


    Since the topic of estradiol is becoming relevant I've been doing some "googling" and found this abstract. I found this to be very interesting that the "normal" dogs have elevated estradiol.

  8. #18
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    I see these researchers are working out of UTK itself: http://lib.bioinfo.pl/auid:1659036

    (above link shows same abstract but with info as to where researchers work happens to be included.)

  9. #19
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    Default Re: Before prescribing Trilostane...(Discussion of UTK adrenal panel)

    UTK college is pretty big:
    The Veterinary Medical Center and the Agriculture/Veterinary Medicine Library are also contained within this modern structure of 246,000 gross square feet.

    The College has research facilities on Cherokee Farm adjacent to the UT Medical Center at Knoxville. Satellite teaching/research facilities are located in Middle and West Tennessee.
    http://www.vet.utk.edu/about/facilities.php

    I looked up the researchers:

    Linda A. Frank, DVM, Professor, Dermatology
    http://www.vet.utk.edu/faculty/frank.php

    Barton W. Rohrbach, VMD, MPH, Associate Professor, Department of Comparative Medicine
    http://www.vet.utk.edu/faculty/rohrbach.php

    Could not find much on Rebekah Mullins, maybe a student?

  10. #20
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    Default Re: Before prescribing Trilostane....

    Interesting. I will definitely have more to say about this, once I am in a mental place where I can say more. Simon has had the UTK test done before he was on trilostane, and then recently. I will say this, the IMS said to disregard the first test, and Dr. Oliver's opinion and put Simon on Trilostane (making me wonder why I spent money on the test in the first place) and since then his hormones went up, (they were high before his cortisol was high enough thus he was diagnosed with atypical cushings, or right when his cortisol went up the first time - I can't remember now, numbers for that should be on his thread) anyway, he has since had another UTK test, which does show Oliver is right, in that it makes the hormones off the chart, but that he does not know what this means is news to me. He told me that high estradiol causes the same symptoms as Cushings. If he has nothing to back that up, no wonder people don't get second tests, and even throw out the results of the first one!

    Quote Originally Posted by lulusmom View Post
    After doing quite a bit of research in the last year on this subject, I've changed my position even more so than Marianne. I personally will no longer encourage members to have a UTK panel at all, unless conventional tests such as ACTH stim and LDDS are negative. Dr. Oliver himself states in his paper entitled "Steroid Profiles in the Diagnosis of Canine Adrenal Disorders" that steroid hormone profiles are indicated when other routine tests of adrenal function are negative (ACTH stim; LDDS; combined dexamethasone suppression/ACTH stim) and the dog still exhibits signs of cushing's syndrome, indicating the likelihood of atypical cushing's disease being present. Dr. David Bruyette prescribes Trilostane to the vast majority of his patients and has all but abandoned Lysodren, reserving it for those dogs that cannot handle Trilostane. He also lectures that you should not jump at having a UTK panel done unless all other tests are negative for cushing's.

    At no time has Dr. Oliver ever suggested that pet owners should always have a UTK panel before starting treatment with Trilostane. I think the rationale behind that is that if a dog has been properly diagnosed with cushing's, it is pretty safe to say that a number of the intermediate steroids are also elevated. So with that being the case, Trilostane would rarely, if ever, be prescribed.

    Some of you may recall that we asked Dr. David Bruyette if he had any concerns about prescribing Trilostane for dogs that have significant elevations in intermediate steroid/sex hormone levels and in those instances, did he recommend an alternative treatment? He answered; "Any adrenolytic agent or enzyme blocker can raise steroid intermediates to some degree. Whether this is an issue clinically depends on the given dog, the dose of medication used, the duration of treatment and concurrent diseases and/or medications." When talking about Trilostane, even Dr. Oliver admits that the long-term effects of elevated intermediate steroids remain ill-defined. Add on top of those opinions that we've never had a member treating their dog with Trilostane report a return of symptoms, despite having perfect 24 hour control of the cortisol.

    I switched my own dogs from Trilostane to Lysodren because Lulu's coat and skin never got better and Jojo's PU/PD never resolved on Trilostane. Well guess what??? It's been a year or better since then and neither one has improved. Lulu is still bald and Jojo is still a drinking fool and a great big pee bucket.

    The veterinary community at large has come a long way in accepting the fact that there are dogs out there with atypical cushing's but I think it's going to take a lot more convincing evidence before the endocrinologists, world reknown or otherwise, will subscribe to the theory that you need to know if intermediates are elevated before prescribing Trilostane. I'd like to see some of that evidence myself.

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