New here - suspect Cushing's in 4.5 yr old beagle mix

Good morning,

We have a rescue dog, Joni, who is 4.5 yrs old, 47lb (she should be 42lb). She was diagnosed with hypothyroidism about 1.5 years ago and is currently on .3mg levothyroxine twice daily. Initially, she responded well, and many of her clinical symptoms improved for a month or so. Then they started to return. They adjusted her dose from .2 mg to the current .3mg. But little was accomplished. She remains lethargic, irritable, sheds like crazy, licks obsessively and recently - which is what caused us greater concern - has started panting and drinking more than usual. She pants at night after being at rest for some time, and at other intermitten intervals inside our AC house. She is also newly exercise intolerant. She has gained wait and has a strong appetite. To us, her belly looks like it's becoming a pot-belly. She's definitely putting on weight - last weigh in was 47, and she's been 42-43lb consist for the past many years. She's always been incredibly fit, so we notice this right away, but others not so much as she just looks 'normal' to some, but we know she's getting heavy. She's normally an incredibly athletic dog, and now she pants like she ran a marathon if we take her just around two blocks. Usually she is happy to hike and run for hours on end. She also is shaking her head intermittenly - her ears appear clear and no infection. And her licking and shedding have become worse.

The Vet ordered a Cortisol to creatinine urine ratio test that we just an hour ago got the results from:

10.6 ug/dL cortisol
195.4 mg/dL creatinine
17 ratio

We are awaiting official response from our vet, but I take it this rules out Cushing? I can't really find the reference ranges in these values online....

We just know our pup is not happy and not herself. If it's not cushing's, does anyone have other ideas as to what this might be? Any thoughts would be welcome and thank you in advance.

Shelton

Welcome to you and Joni — we’re really glad you’ve found us! Boy, I have to admit that her symptoms are so classic for Cushing’s that it’ll be very surprising if those UC:CR results are indeed within normal range because, if so, that does make Cushing’s quite unlikely. One question, though: was the urine test based on only one sample, and was the sample obtained at home or at the office? (I guess that’s actually two questions ;-) We’ve been told that pooling samples obtained on three successive mornings at home can result in a more accurate picture, since cortisol production can be variable and you also want to eliminate the effect of stress. As far as stress, that could artificially elevate the reading, and that doesn’t seem to be Joni’s issue. But still, I’m curious to know how the sample was obtained.

Also, have there been any other abnormal results on Joni’s lab profiles other than her thyroid? Cushpups commonly exhibit elevations in liver markers and cholesterol, and also sometimes have abnormalities in certain blood cell counts (platelets and white cells). Also urine is typically quite dilute with low specific gravity. Urinary tract infections are also common. If Joni’s blood and urine panels have all been normal, that also makes Cushing’s unlikely. But if she’s had other results that are consistent with Cushing’s, that makes me scratch my head even further and makes me wonder whether you might still want to advance to a more specific diagnostic Cushing’s blood test even in the face of these urine results.

I’ll go ahead and close for now as opposed to peppering you with more questions! But once again, we’re very glad you’ve found us and we hope we’ll be able to help chart the best path forward.

Marianne

Hi Marianne,

Wow thank you for the fast reply - I have to say I feel some relief just having someone else thinking on her scenario in such a thoughtful way! I really appreciate it. We went through a string of not so great vets for a number of years chasing the thyroid issue, and finally found one we liked, only for her to leave the practice. Now we’re basically with a new vet every time we go in.... I think they are generally well intended, but I just fatigue of not feeling like we have a partner to really help us figure it all out.

So Joni has always had some irregularities with her lab work. Her most recent physical and full blood panel was done in January of this year, so know that it’s now 7 months ago from whatever is happening today. But here are the ways she was irregular back then - I don’t really know what any of it means, and wasn’t really given an explanation from our vet - my emails weren’t responded to at the time (different vet then who we corresponded with this past week for the urine test, though they are all a part of the same vet practice here in Philly).

Hemoglobin - slightly high outside reference range; 21.0
MCH - slightly high; 26.1
Reticulocytes - high; 129
Glucose - low; 59
Albumin - high; 4.3
Creative Kinase - high; 245

And since you mentioned cholesterol specifically, it was normal but towards the upper limit within the given reference range at 321. All other values were within the reference ranges, but some other values were right at the very top or very bottom of the ranges. Let me know if you want to know those values.

Also, her T4 even on supplementation always remains low - it was at 1.3ug/dL still. I never have understood why we can’t get that to go up more when she’s on .3mg twice daily.... feels like it should be a bit higher. When she was diagnosed, she was at .8, so I guess it is all relative... but feels odd.

Thank you again and please let me know if you have any other questions - I’m grateful to have someone who is thoughtfully interested!

Best wishes,

Shelton

Thanks so much for all this additional information! Joni’s situation definitely remains perplexing :-(((. I’m not sure what to make, if anything, of the particular abnormalities that you’ve noted. They are not lab values that we commonly see associated with Cushing’s. The liver markers that I was talking about previously are the ALKP (or sometimes noted as ALP) and ALT. Elevated levels of ALKP (sometimes exceedingly high) are very typical of Cushing’s, as are moderate elevations in ALT. If those values were both normal for Joni, then her clinical picture is definitely odd: observable symptoms that are very common with Cushing’s, but lab values that are not really consistent at all.

I wish I was more knowledgeable about thyroid abnormalities, but I know only enough to be dangerous, as they say. Low thyroid can be a primary problem in a dog, but it also can be secondary to other conditions, of which Cushing’s is one. My own Cushpup was initially diagnosed with hypothyroidism based on low T4 readings, but when his symptoms did not resolve with supplementation, we proceeded with further diagnostics and found that he indeed suffered from Cushing’s, as well. I’ve since learned that it’s probably best to perform a more complete thyroid panel prior to beginning thyroid supplementation, as opposed to simply relying on basic T4 levels. More complete thyroid analysis can help guide supplementation decisions— sometimes supplementation is necessary and sometimes it’s not, especially if the low readings are due to another condition. Unfortunately, the difficult part is that if owners want to retrace their steps and have a complete thyroid workup done, the dog has to be removed from supplementation for several weeks in order for new diagnostic testing to be accurate. As an example as to how complex thyroid testing can be, here’s a link to an informational page about thyroid testing found on the website for Michigan State’s Veterinary Endocrinology service:

https://cvm.msu.edu/vdl/laboratory-s...nction-in-dogs

I know I’ve probably gone overboard here with my thyroid discussion, but it just caught my attention since Joni has not been responding to her supplementation in the way you would have hoped or might have expected. In honesty, Joni’s situation is puzzling enough to me that unless your local vet comes up with some reasonable diagnostic suggestions, I’d encourage you to request a referral for a consultation with an internal medicine specialist. I’m sure there are many private specialty practices in the Philly area, but if I’m not mistaken, you’ve got one of the premiere veterinary schools of the nation located there : UPenn. I’m confident they’ve likely got an outpatient clinic there that accepts patients for diagnostic consultation. Either way — UPenn or a private specialty practice — you may find that your money would be well spent to get the opinion of an endocrinological expert. Clearly, something has changed significantly for Joni, and it may take some searching to figure out exactly what’s gone wrong. But specialized professionals may be able to help you find the answers more quickly.

I’m so sorry that I don’t have more immediate answers for you, but please do feel free to continue asking more questions and discussing more options, OK?

Marianne

Thank you Marianne! I very much appreciate your thoughts and the links. We're going to follow-up with the vet again tomorrow - it seems since it has been 7 months since we ran a complete blood work on her, maybe it's time to recheck. And maybe that will give us some new insight of something has shifted / changed more recently. Just because you inquired, the ALKP markers were within normal range back in January. And though I'm also no expert on the thyroid issues, I will share when she was diagnosed we did have a full panel with free T4 and T3 and the thyroid stimulating hormone as well - but I agree, it is still puzzling to us that she hasn't responded quite the way we thought she would on supplementation.

Once we have some new markers to go on I will write back in, but thank you again for your support! It means a lot just to have someone else consider all this.

Best wishes,

Shelton and Joni

Dear Shelton, just a quick note to let you know that I’ve moved your thread here, to our main Questions and Discussion subforum. When I replied to you earlier, I hadn’t noticed that your thread was located on one of our subforums that receives less “traffic.” Hopefully more folks will see our conversation here, and join in alongside us ;-).

Marianne

Hi Shelton,

A belated welcome to you and Joni!! I just wanted to mention that I took my boy, Harley, to UPenn (Ryan Veterinary Hospital of the University of Pennsylvania) and thought it was well worth the 2 hour drive, now, this was almost 10 years ago. If you have any questions for me please do not hesitate to ask.

Lori

Hello Marianne and Lori,

I just wanted to give an update since we've had some news. Joni's concerns have remained much the same since I wrote in, and we got a little vet fatigue and she wasn't getting worse so we just acquiesced for a time. But in February we took Joni for her standard physical, and her ALP came back high - in the 300s. The vet recommended rechecking this month. We just rechecked, and it's high again - this time higher - just shy of 400. Her ALT has gone up too, though still in the normal range she's jumped from usually being in the 40s to 94. She also has developed a new balding spot on the very tip of her tail, which is disconcerting to us, together with the other symptoms I shared before (drinking more, eating more, maybe peeing a bit more, darkening of her skin on her belly, and shedding). So, after some discussion, and though the levels aren't exceedingly high like other cush pups (I've read they can be over 1000??), the vet agreed that it's reasonable to do the LDDS testing.

So my questions are - do you ever see cush diagnosed with ALKP levels in the 300-400 range?
Any advice on what to consider relative to the LDDS testing / how to interpret results?

We are scheduling her after our next pay day, so she won't go back until March 26.

Finally, I am just curious - do you ever see behavioral impacts with cush? Joni has some anxiety based behaviors, and I'm just wondering if she does have cush, could it be making her more irritable?

Thank you in advance and hope you are well!

Shelton

Hello again, Shelton, and welcome back to you and Joni! Under the circumstances that you've described, I do believe it makes sense to go ahead with the LDDS testing. One of the earlier perplexing pieces of Joni's profile was that she was exhibiting observable symptoms that are consistent with Cushing's, but her lab results did not follow suit. Now that you are seeing increases in her ALP and ALT, I do think that further diagnostic testing merits a second look. As far as abnormal liver levels exhibited by Cushpups, the range we see is broad. Even though Joni's levels are not exceedingly high right now, I do think it's significant that they are elevating. This pattern is something that we commonly seen in Cushpups prior to treatment. So depending upon the stage and duration of untreated Cushing's, the elevations can vary from relatively mild or moderate, to extremely high.

As far as proper interpretation of LDDS results, here is a link that goes into quite a bit of detail and has been very helpful to me in terms of making sense of the results:

https://www.dvm360.com/view/clinquiz...n-test-results

Last but not least, I'm guessing the most common behavioral changes that people report with Cushing's are probably increasing lethargy and exercise intolerance. Whether or not Cushing's might be responsible for making Joni more irritable, I don't know. But if a dog is generally feeling poorly in terms of ravenous appetite and excessive thirst/urination, etc., it wouldn't surprise me to think that this could result in a dog being more irritable, as well. I know those things would make *me* feel crabby!

So all in all, I think it is reasonable to move forward with the testing. Definitely check back with us when the results are in, OK?

Marianne

Hi Marianne,

Thank you for all of your help! I wanted to report that Joni went in for her test on Friday, and the vet has contacted us to share she has Pituitary Dependent Cushings. They are going to start her on a trilostane (sp?). They said her levels were consistent with cushings, but low, and that we had caught it early. Her test results were:

Cortisol - baseline 8.6 ug/dL
Cortisol - 4 hr post dex .3 ug/dL
Cortisol - 8 hr pst dex 2.9 ug/dL

I am curious to know - and I think I've seen other threads about this and can have a look, but recognizing that she will now be on another maintenance medication (she is already on the levothyroxine for hypothyroid) I am really eager to know of any resources for costs. The vet said the trilosane for 1 month would be $82! Joni is worth every penny but any resources that you know of I would be so grateful for! Thanks
Joni mom