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Thread: Potential Cushings diagnosis

  1. #1
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    Default Potential Cushings diagnosis

    Hi,
    I found this forum while looking up info on Cushings in dogs, and am hoping you all can help. My dog Bella is looking at a potential Cushings diagnosis, and am wondering A) if her combination of symptoms sounds familiar to anyone, and B) What are the risks of treatment vs waiting, since right now she doesn't have very much in the way out of outward symptoms.

    To back up a bit, Bella is a ~50 lb Husky/Samoyed/northern breed mix. We rescued her 5 years ago, and the vet estimates her current age is around 8-10. she was diagnosed with hypothyroidism about 2 years ago about 6 months after a severe bout of acute Pancreatitis, Gall bladder infection, UTI, and a blood clot (all at the same time). For the 6 months after that her energy level was low, losing fur, skin turning black, etc, recurrent diarrhea, plus another UTI. I asked our vet to perform a thyroid test, and her T4 levels came back very low (<50). After starting the thyroid supplement, it was like she was a new dog, fur grew back, energy back up, stomach problems went away. Since then she's been doing great except for another gall bladder infection about a year ago and 2 additional UTIs within the past year. She's also had 2 blood clots to go along with the gall bladder infection.

    Fast forward to now, and a month ago we took her to get her first dental cleaning in about 3 years, and when they did the pre-anesthesia blood work her ALKP levels came back high (432 vs 212 max normal range). They were elevated on her previous blood work as well but not as high, although the ref max was different for that test (275 vs 131 max normal range) All other liver enzymes and other blood test levels came back normal. Our vet recommended a followup to a specialist given her history of gall bladder disease. We went to her internal medicine specialist who did an ultrasound. Ultrasound showed no issues with her liver or gall bladder (other than some stones that were pre-existing but not obstructing anything) but did show another blood clot. To try to determine the source of the recurring blood clots, the doctor did a urine cortisol/creatanine test (sample collected in the morning about 5 days after the initial visit). I just got back the results, which showed an high level of cortisol (22 vs <13). Based on this, the recurring blood clots, and the elevated ALKP levels, the Dr is thinking it may be Cushings and wants to do the LDDS test next Monday. Other than the internal readings, she's not showing a ton else in the way of symptoms. Her appetite is completely normal, although she has been drinking slightly more water over the last month or so, but we had just chalked that up to summertime heat. She doesn't drink a lot of water normally, so its not a huge total amount of water she's drinking, but it has been maybe a 25% increase from her usual. She's also been panting a lot more over the past several weeks(waking up panting during the night occasionally), but has seemed better the past few days, so not sure if that's just the heat as well. She's not peeing more frequently (she has always "marked" like a boy dog on walks, but otherwise only needs to go out once or twice in addition to her two daily walks). She has been having intermittent incontinence issues for the past few months. We put her on Incurin for a bit, but she got ALL of the side effects, so now we're just doing a tiny (.5mg) does once a week (vs 1 mg/day dose she was on that caused side effects), and that seems to be enough to limit those issues for the most part, but no side effects. Her energy levels seem pretty normal (active bursts around morning and evening walk and then dinner time, pretty relaxed and chill most of the rest of the time).

    Hoping I can get some advice on whether this might actually be Cushing's or just some weird coincidences and false positives. Given her complex medical history, its hard to tell what's causing what, and I definitely don't want to have her end up on any drugs that she doesn't need (already taking enough drugs as is!). Sorry for the huge info dump, and thanks for any help. Also definitely don't want to put her through more tests than necessary, so understanding what's worth doing and what isn't would be helpful.


    -David

  2. #2
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    Default Re: Potential Cushings diagnosis

    Hi David,

    Welcome to you and your sweet girl, Bella!

    Some of what you describe is consistent with Cushing's - the pancreatitis, reoccurring UTIs, and blood clots are found with uncontrolled elevations of cortisol. But with all Bella has going on I would expect her cortisol to run higher than normal. Cortisol is one of the fight or flight hormones and any time stress is present, external or internal, the cortisol rises in response as it is supposed to do. My Squirt was also first suspected of Cushing's from pre-dental testing and in subsequent Cushing's tests - LDDS, HDDS, ACTH, and UTK panel - she tested positive for Cushing's. HOWEVER, when we did the abdominal ultrasound a tumor was found on her spleen. Once that tumor and half her spleen were removed, her cortisol returned to normal levels. The cortisol was high due to the tumor and caused false-positives on ALL her testing. So I am always very cautious when a pup presents with many issues and Cushing's is suspected.

    It would seem the thyroid was responsible for many of the other signs of Cushing's - hair loss and dark skin. Diarrhea is not typically a sign of Cushing's. The ALP, or ALKP, readings we see are MUCH higher than what Bella is showing - we see those values in the 1000's, not just a 100 or so points above normal. We typically also see changes in other liver values as well as kidney values, the triglycerides, cholesterol, neutrophils, monocytes, very dilute urine, and an abnormal UC:CR, which compares cortisol to creatinine. An abnormal UC:CR does *not* mean Cushing's however - it simply means SOMETHING is off and further testing is needed. On the ultrasound we expect to see one or both adrenal glands enlarged OR one enlarged and one very small, even atrophied. Normal adrenal glands are a rarity. Signs in Cushing's are just as important as the test numbers partially because those lab results can indicate many thing other than Cushing's. So without obvious signs such as a ravenous appetite 24/7, loss of house training *without* the presence of an UTI, heat intolerance, hair loss, pot belly, panting for no discernible reason, exercise/jumping intolerance, to name a few, I am again suspicious that something other than Cushing's could easily be in play. The LDDS is particularly known for returning false-positives when any non-adrenal condition is present....like UTIs.

    So that is *my* take - that something OTHER than Cushing's is responsible for what you are seeing and that that something may well cause false-positives on the cush testing. Bear in mind tho - I am coming from my own experiences...which include a second dog diagnosed with Cushing's when she had COPD, anal gland disease, and many other conditions she was battling. A necropsy (autopsy for animals) revealed that she did NOT have Cushing's after all. So my advice, proceed with an open mind and a willingness to strongly question any diagnosis of Cushing's unless her signs become much stronger and her labs reveal more consistency with Cushing's.

    I am glad you found us and look forward to hearing more about your sweet girl. Regardless of her final diagnosis, you are both family here now and we will want to know how she is doing.
    Hugs,
    Leslie
    "May you know that absence is full of tender presence and that nothing is ever lost or forgotten." John O'Donahue, "Eternal Echoes"

    Death is not a changing of worlds as most imagine, as much as the walls of this world infinitely expanding.

  3. #3
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    Default Re: Potential Cushings diagnosis

    Hi Leslie,
    Thanks for your thoughts. I too am a little skeptical that we're seeing false positives, although I'm also not sure what else might be the issue, unless her existing blood clot is causing all the problems, although the vet didn't seem to think so. She has been panting a lot more over the past few months (and again today, even though its not that hot out here). She's also had multiple abdominal ultrasounds over the past year, and no abnormal growths or anything detected. Do you think it's still worth proceeding with the LDDS test? I guess if its negative that'll rule things out, but somehow given her medical history I doubt it'll end up being that simple.

    Thanks,
    David

  4. #4
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    Default Re: Potential Cushings diagnosis

    What is the sensitivity of the LDDS test to external stressors? There's a decent chance of thunderstorms tomorrow, and Bella tends to freak out a bit when she hears thunder. I'm worried that if she does the LDDS test tomorrow and hears thunder, it'll artificially bump up her cortisol levels.

  5. #5
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    Default Re: Potential Cushings diagnosis

    I'm not sure the LDDS is sensitive to that sort of short term stress however the ACTH is. A dog who gets stressed simply going to the vet can return a high reading on the ACTH. As for proceeding with the LDDS, personally I wouldn't right now. The normal ultrasounds is another red flag about a Cushing's diagnosis. The adrenal glands would show as abnormal in a cush pup due to the extreme work they are doing producing cortisol. They change in one of two ways - both enlarged which indicates the pituitary form, or one enlarged and the other very small or atrophied which indicates the adrenal form. I wouldn't expect a normal LDDS in a dog with as much going on as Bella has so I'm not sure it will tell you anything valuable. But again, that is what I would do in your shoes. She is your baby and you must do what you feel is right for her. And we will be right here with you all the way.

    Hugs
    Leslie
    "May you know that absence is full of tender presence and that nothing is ever lost or forgotten." John O'Donahue, "Eternal Echoes"

    Death is not a changing of worlds as most imagine, as much as the walls of this world infinitely expanding.

  6. #6
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    Default Re: Potential Cushings diagnosis

    David, I've asked, Lori (Harley PoMMom) to come take a look at Bella's story. She is one of our Admins and may well have a different outlook to present.
    "May you know that absence is full of tender presence and that nothing is ever lost or forgotten." John O'Donahue, "Eternal Echoes"

    Death is not a changing of worlds as most imagine, as much as the walls of this world infinitely expanding.

  7. #7
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    Default Re: Potential Cushings diagnosis

    Hi David, and a belated welcome to you and Bella!

    Due to the absence of strong clinical symptoms I'm inclined to believe that Bella doesn't have Cushing's. Two diseases that Bella does have, hypothyroidism and pancreatitis, have the ability to cause blood clots and will elevate the ALP levels. Has Bella been tested for heartworms? Heartworms are another health issue that can cause abnormal blood clotting. Where was the blood clot located that showed up on the ultrasound?

    Lori

  8. #8
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    Default Re: Potential Cushings diagnosis

    Thanks all for the ideas, it's very much appreciated. Just as an update, I put off the LDDS test, but am reconsidering and planning to try it next week. She hasn't been tested specifically for heart worms (unless its done as part of a regular exam and I just don't know), but she's consistently been on heart worm preventative since we adopted her, and her symptoms don't seem to line up with heart worms. Her blood clot is in the abdominal part of the aorta, it's blocking about 50% of the aorta, although she's had a similar/worse one in the past and also showed no symptoms from it.

    Also, just to clarify, her pancreatitis and gall bladder infections were 2.5 and 1 yr ago, respectively. Since then, she's been quite healthy except for what seems like a yearly UTI that she gets and her recurring blood clots, (not full blockage, just partial), although the blood clots don't really present any symptoms that I can tell.

    I've also noticed that her coat is starting to thin again. The skin on her tail is very visible now, and it wasn't a few months ago. It's also easier to see the skin on her back, which I also couldn't do 6 months ago. It's nowhere near as bad as before her thyroid diagnosis, but definitely different over the last few months than the 2 years between then and her hypothyroidism diagnosis. Her T4 levels are still good, so I don't think the issue is with her thyroid supplement. I'm wondering if she may just have a fairly early, very slow moving version of Cushing's. The adrenal glands were both small on ultrasound, although the Dr did say one was slightly larger than the other. Maybe with them starting smaller than normal she may be producing excess cortisol now, but not as much as a dog who started with normal size adrenal glands? I've been doing a bunch of research, and even though she's not showing some of the typical signs (excessive thirst, potbelly, etc), I can't find anything else that would explain the increased ALP, increased Cortisol ratio, history of blood clots and infections/UTIs, excessive panting, worsening incontinence, and now hair thinning in an otherwise (behavior/energy-wise) seemingly healthy dog. (panting and hair thinning have only been over the last ~3ish or so months, and her energy level is down slightly, but she's still goes on walks and actively jumps and runs for food and treats, something she did not do for the few months prior to her hypothyroidism diagnosis). If anyone has ideas of other possibilities, I'm definitely all ears. She likes to give us a challenge by always having the obscure symptoms or side effects from things so figuring out what's going on can definitely be a challenge (i.e., she is almost completely asymptomatic for blood clots and UTIs, but got ALL of the rare hypothyroidism effects, and has had rare side effects to various medications she's been on previously like incurin and chloramphenicol).

    My current plan is to go to her regular vet and check to make sure her thyroid (T4) levels are still good and that she's UTI-free (since sometimes its hard to tell). Assuming it's neither of those issues, I was going to go for the LDDS test. I'll follow up afterward, and would definitely love to hear any other thoughts on alternative diagnoses.

  9. #9
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    Default Re: Potential Cushings diagnosis

    According to Dr. David Bruyette, who is a veterinary endocrinology expert, monitoring thyroid supplementation using the T4 post pill isn't as accurate as once thought:
    Once canine hypothyroidism has been diagnosed, what are Dr. Bruyette’s recommendations for laboratory monitoring? He says that many veterinarians, including those attending this CVC session, were taught that they should draw blood for T4 testing from four to six hours after the thyroid hormone pill was administered. Dr. Bruyette says, “The percentage of T4 that is absorbed from the gut varies from 13% to 87% in a given dog from day to day. So, on Monday, the dog may absorb 13% of the dose; on Tuesday, it may absorb 87% of the dose. The post-pill test is severely affected by the intrinsic ‘weirdness’ of the T4 bioavailability. Therefore, the post-pill test is probably physiologically meaningless.”

    So, is there a way to confirm a dog is euthyroid when it is receiving thyroid hormone supplementation? There are two options: thyroid-stimulating hormone (TSH) measurements or free T4 by equilibrium dialysis (fT4 by EqD). If the TSH is normal, the dog is euthyroid. If the TSH is high, it needs more thyroid hormone; if it’s low, the dog is getting too much of the hormone.

    But if you read the companion article “Canine hypothyroidism: Shield your patients from overdiagnosis,” you may have already spotted the problem with this option. In that article, we stated that with the TSH assay, 25% of hypothyroid dogs have a normal TSH concentration to start with (because the assay does not work well). Therefore, to use TSH assays to monitor a dog on hormone replacement therapy, you must have had a pre-treatment TSH result that was high. Without that, you simply can’t interpret what the TSH concentration means now.

    The other option is to measure fT4. After two weeks of thyroid hormone supplementation, fT4 concentrations over a 24-hour period are constant. With the fT4 by EqD test, it doesn’t matter what time of day or when in relation to the pill administration you collect the blood sample, because the concentrations don’t fluctuate.
    http://veterinarymedicine.dvm360.com...dates?pageID=2

  10. #10
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    Default Re: Potential Cushings diagnosis

    Hi,
    Wanted to revive this, since I have some more updates on Bella and wanted to get some thoughts, since we're getting ready to start Veotryl treatment. Shortly after previous posting, performed a LDDS test, which came back negative. However, over the next 2 months, her symptoms grew worse, particularly after she built up a tolerance to the Incurin we were using to treat her incontinence. When we stopped the incurin and switched to Proin, her incontinence improved, but she became very PU/PD (drinking about 300-400% her normal water intake, lots of pee). Our vet performed a complete set of bloodwork, urinalysis, CBC, etc. Everything came back normal (no signs of infection, no kidney issues, etc), with the exception that her ALKP values had increased again up to 790 (previously 490). We repeated the LDDS test (now that her PU/PD was worse and off the influence of the incurin) and this time it came back positive (3.9 initial, 2.0 at 4 hrs, 1.8 at 8 hrs, reference range is <1.4). We also rechecked her T4 and free T4 levels, and those were seen to be well controlled (also her typical first sign of hypothyroidism is diarrhea, which she doesn't have).

    With that info, plus all the other cushing's signs she's been showing (hair loss on tail/along spine, heat intolerance, increased panting, decreased energy levels), the vet diagnosed cushings. We are starting a very low dose of Veotryl (.5 mg/kg), but I wanted to know what to expect with starting this treatment. We don't start until next week (they had to order the right dosage of the medicine), and we already have schedule an electrolytes check at 1 week and an ACTH stim test at 2 weeks. However, any experience with this drug and risks/concerns/issues/etc to be aware of would be helpful.

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