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  1. #1
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    Hello everyone my name is Chris and my wife Danielle are owners of a great 7 year old Vizsla named Izzi who was recently diagnosed with Cushing’s. She was diagnosed in late February and started on Trilostane 60 mg. After about a month her lab values were drawn which indicated it was working. Unfortunately, clinically it wasn’t. She was still having multiple accidents in the house, she started to breath weird when she slept, along with increasing tremors. Her waking up at night has gotten worse 2-3 times a night. We even tried Desmopressin eye drops to see if she was in DI as well. After 3 days there was no improvement. We had urine cultures drawn on a Thursday which showed nothing, by Sunday she was peeing all the time and having accidents all over the house. We thought we were losing her on Monday but come to find out after a UA she had a UTI and was started in Antibiotics. The uti has resolved but other than that we still feel like we are getting nowhere! Having less accidents but still drinking a ton, wanting out 2-3 times a night and tremoring as she rests! Does this all sound familiar, and is there anything else we can do?? She’s had a ultrasound and it definitely is pituitary in origin.

    Thanks
    Chris and Danielle

  2. #2
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    Hi Chris and Danielle,

    Welcome to you and Izzi! Could you get the results of all tests that were done and post those values that are abnormal? Also, if you would post the results of all her monitoring ACTH stimulation tests that would be really helpful to us. How much does Izzi weigh? And besides the antibiotic, is she on any other herbs/supplements/medications?

    I sure am sorry for the circumstances that brought you here but glad you found us and we will help in any way we can.

    Lori

  3. #3
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    We sure will get results and post them, Izzi weighs around 58-60 lbs. Today she’s had two accidents very frustrating beginning to wonder if we should just take her off Trilostane? Symptoms don’t seem to change, I know my wife is getting frustrated with the entire situation! Beds, carpet and couches taking a hit! How do you know when it’s time? Will things get better?

  4. #4
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    Welcome from me, too! That’s great that you’ll be getting those test results, especially the results of that one-month ACTH monitoring test. That result will be key in helping us evaluate whether or not Izzi’s current dose of trilostane is likely to be optimal. We always like to see the actual numbers, themselves, because some vets are unaware that desired therapeutic levels of cortisol in dogs taking trilostane are significantly lower than the “normal” range for dogs who don’t have Cushing’s at all. So it’s possible that Izzi simply needs a higher dose of the medication to be effective.

    Also, regarding her trilostane, I hope you’ve been told that she needs to be given her trilostane along with a full breakfast each day, including on the day when a monitoring ACTH test is run. In order to be metabolized properly, trilostane needs to be given with food. On testing days, the ACTH should be completed 4-6 hours after dosing.

    One more thought: even in the event that Izzi’s monitoring ACTH showed that her cortisol fell within the desired therapeutic range, you might want to try switching her to twice-daily dosing. Especially since her symptoms really seem to rebound at night, it may be the case that the medication is being metabolized quickly and allowing her cortisol level to rebound long before her next daily dose is due. When symptoms rebound or are poorly controlled even when cortisol levels seem appropriate, an alternative is to split the daily dose in half and administer the medication every 12 hours. So in Izzi’s case, for example, she might do better if she was given 30 mg. every 12 hours as opposed to 60 mg. every 24 hours.

    But before speculating further, we really do need to see the actual test numbers. So do let us know about them as soon as you can, and then we can help you problem-solve in the hope of improving things for all three of you!

    Marianne

  5. #5
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    Hello, we just received IzziÂ’s test results since her diagnosis in February. We were notified in February of an elevated Alk Phos 295 (5-160). A week or two later she started having accidents and they started the work up for CushingÂ’s especially when they noticed her urine was very diluted.

    1st low dose dexamethasone test 2/20/19

    4 hr= 73 (0-30)
    8 hr= 76 (0-30)

    Izzi was started on 60 mg trilostane once a day. At this point she was just having accidents periodically. After two weeks symptoms werenÂ’t getting better, still having accidents, up at night begging for food and water or too go outside.

    3/13/19
    Cortisol baseline 31
    Cortisol 1 hr post ACTH 129 (220-550), still symptoms of polyuria and polydipsia. After researching and talking with Vet we decided to split dose 30 mg once in morning after meal, and once in evening after meal.

    Symptoms getting worse contacted Vet decided to pay for further testing went to Blue Pearl Inrernal Med Vet. She received an abdominal Ultrasound (no adrenal mass), she started tremoring a week or two prior and respiratory has gotten more labored. At this point specialist said to start ddavp eye drops for a few days to see if she was in DI ( eye drops didnÂ’t do anything), also increased trilostane to 90 mg and got urinary cultures tests were clean. Two days later Izzi contracted a UTI and started on Bactrum. Still no changes on 90 mg of trilostane. At this point she is on 60 mg BID of Trilostane and still having occasional accidents, still labored breathing at night, still restless at night. She also still has polydypsia and polyuria. Not sure what we want to do at this point and wondering if we should just take her off meds and treat with herbal options.

    Thanks
    Chris

  6. #6
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    Chris, thanks so much for this additional information. I'm surely sorry that Izzi is having such a rough time, as are you and your wife. However, aside from any of the other issues, I'm very worried about the increase in Izzi's trilostane dose, apparently without the benefit of any additional ACTH monitoring testing since mid-March. At that time, her post-ACTH cortisol level translated into 4.7 ug/dL, which are the units with which we're most familiar here in the U.S. That level falls within the ideal therapeutic range for trilostane treatment, and therefore you'd want to be cautious about increasing her dose further, especially since it sounds as though the test was performed after only about two weeks on the trilostane. Even when doses are left unchanged, cortisol levels tend to continue to drift downward during the first month of treatment.

    I do understand the initial shift to 30 mg. twice daily, since that was a suggestion that I had even made myself. But the subsequent dosing increases -- first to 90 mg. and then 120 mg. as daily totals -- definitely ought to have prompted additional ACTH monitoring testing. The acceptable post-ACTH treatment "zone" ranges from approx. 1.5 - 5.0 ug/dL, so a bit of downward movement to her cortisol level might have been OK. But to go so far as to double her dose without monitoring testing is very, very worrisome to me. It's possible that her cortisol has now dropped to a level that is dangerously low. It's also possible that other blood chemistries may be "off" due to the suppressive effect that trilostane has on aldosterone, another adrenal hormone. Aldosterone controls the balance of potassium and sodium in the body, and overdoses of trilostane can lead to serious imbalances in those chemistries, too. This can cause an Addisonian condition, of which excessive thirst, urination and tremoring can be symptoms. That's the hard part -- excessive thirst and urination can be caused by low cortisol or low aldosterone just as they can be caused by high cortisol. So it's very important that both cortisol levels and basic blood chemistries be monitored in conjunction with any increase in trilostane dosage, and why outward symptoms can't be relied upon alone when making dosing increases. Has neither the internist at Blue Pearl nor your regular vet recommended monitoring testing after these dosing increases? For Izzi's safety, you need to request the testing yourself, if they've not already talked with you about it (which they definitely should have!).

    Now going back full circle, can you tell us more about what was going on when she was initially diagnosed? What led to the initial blood test that showed the elevated ALKP? Was it just a standard wellness test, or was she ill in some way? Since you say she didn't start having the accidents until 1-2 weeks after you were notified of the blood results, I'm wondering whether anything else was abnormal for her at the time. Any other symptoms or any other abnormal lab results at all aside from the ALKP and dilute urine? At this point, I'm just wondering about the actual accuracy of the Cushing's diagnosis. An ALKP of 295 is not very elevated in terms of Cushing's -- we've had many dogs here with ALKP readings in the thousands. Literally. So I'm just trying to track back through the original diagnosis, especially since the low dose dexamethasone test is vulnerable to returning "false positives" when dogs are actively suffering from illnesses aside from Cushing's. Heck, I'm even wondering whether she may just be suffering from an insufficiently treated severe chronic UTI. It can be really hard to get adequate cultures from very dilute urine samples, and thus accurately identify the correct antibiotic that's needed to eradicate the infection. Does the internist have any other thoughts about the situation, other than just increasing the trilostane? I would have hoped that she would be more helpful as far as trying to get to the root of the problem...

    So to recap, I'm really worried about Izzi's cortisol and blood chemistries subsequent to the trilostane increases. I think you need to repeat a monitoring ACTH and basic blood chemistry panel ASAP. And yes, perhaps to consider discontinuing the trilostane altogether since she has only seemed to worsen since starting on it. But once again, it'll help us to find out more about her initial diagnosis and any related abnormalities at that time.

    Marianne

  7. #7
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    Marianne, wow you are well versed in this disease, may I ask are you a Vet or medically trained? Now to answer you questions which led to IzziÂ’s diagnosis. We moved to a new house in August and Izzi started begging for food more frequently which was very unlike her. Somewhere around late November or December she was peeing the bed and Danielle brought her into the Vets where they said she a UTI and her fat pad near her urethra was obstructing it. They also started her on a drug Porin for urinary incontinence to try for a couple weeks. In February yes Izzi went in for her annual check up in February and had regular labs drawn which indicated the slightly elevated Alk Phos. Shortly after this annual is when IzziÂ’s started showing symptoms of urinating in the house and polydipsia. We thought she might have a UTI so my wife brought her in and the drew a UA, but the specific gravity was very low, so they said to come back the next morning and turn in a draw after her first urination of the day. Interestingly enough this urine had an even lesser specific gravity. It was after this the vet said she was concerned she had CushingÂ’s and led to the testing.

    As far as further testing, we were due to having her second test but she was displaying worse symptoms so we told our vet we want to take Izzi to get a second opinion even though Michigan State UniversityÂ’s labs showed otherwise. They agreed and sent us to Blue Pearl, after having an Ultrasound, she recommend to increase dose to 90 mg but no more. We didnÂ’t see any changes on 90 mg after two weeks and actually seemed worse so I said no more 90 mg, and have been on 30 mg BID for a week now. I too havenÂ’t liked how sheÂ’s being managed and had my wife call the vet yesterday asking to have labs drawn because I have the same exact concerns!! I told my wife IÂ’m concerned with her electrolytes and Addisons symptoms as well! They said they were going to consult with Blue Pearl and call us back Tuesday or Wednesday which which will be tomorrow. Ive questioned everything one of the reason IÂ’ve reached out to this website is because she deteriorating so fast which makes me wonder is this a brain tumor or mismanagement!

  8. #8
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    Chris, thanks for again providing this additional information. I’m very relieved to hear that Izzi was never increased to 120 mg. daily, but is instead back to 30 mg. twice daily. As you already know, though, it will still be important to see whether or not her labwork is within a safe range, though.

    We’ll be really interested in hearing what Blue Pearl advises in terms of additional next steps. The fact that Izzi seems to have responded so poorly to the trilostane still raises questions in my mind as to whether or not elevated cortisol was/is her core issue. Before speculating further myself, though, let’s see what Blue Pearl suggests.

    And nope, I’m not a vet — just a dog parent. I’ve been active on canine Cushing’s forums for over a decade, though, so I’ve read an awful lot of Cushing’s stories over that time ;-).

    Marianne

  9. #9
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    Marianne, well you are very well read! I spoke with our vet today and got Izzi in this morning for labs. She just called me and said that her electrolytes are WNL but her Liver Enzymes have increased. She’s concerned with the fact Trilostane isn’t working clinically. She hopes to have the cortisol levels tomorrow and a discussion with Blue Pearl for any recommendations. At this point I feel like we are losing the battle and beginning to know what our options are beside putting her to sleep! She seems to be rapidly declining from a symptom stand point. She said since we’ve been able to get a strong hold on this we’ll make some calls and see if anything works if not we’ll have to look at quality of life. Not the words I wanted to hear!

  10. #10
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    Turning back to the abdominal ultrasound again for a minute, were irregularities noted in any of Izzi’s internal organs, especially her liver? And as far as the adrenal glands, you’ve told us that no masses were noted. Were the glands noted as being enlarged, however?

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