Thoughts on Possible Cushings? (Kiwi has passed)

[Mark4124]

I have a 12yr old male diabetic Schnauzer named Kiwi. Yes, I said it, diabetic. :) He has been well maintained for about 2yrs on 12iu of NPH insulin 2x a day with Nutro low calorie food (high fiber and low carbs, incredible food for either weight control or diabetes). He lost a boatload of weight when he was first diagnosed and I changed to the Nutro, going from 32 to 26lbs. But then he stabilized in weight and everything was going along fine. More recently however I have noticed what I would call some degree of negative body composition change. His spine has become more prominent as have his ribs. He still weighs the same though. I have tried feeding him more and will continue doing so but that makes for a hard time controlling his glucose. I took him to the vet the other day and she was beyond herself that he would take so much insulin. But really, what can I do, that is what it takes in his case. We did an X-Ray and chemistry. For the most part everything was either normal or in-line with aging. I am questioning Cushing's though. 1. Due to what appears to be muscle atrophy (spinal prominence), 2. He drinks like crazy, 3. He requires that ungodly level of insulin. Vet isn't crazy about my theory and wants to do ultrasounds and a bunch of other expensive tests that I don't think are particularly indicated given what we have found thus far. With respect to the labs:

Urine specific gravity was 1.033 No Reference Range (RR) noted on labs
T4 1.1 RR 1.0-4.0
MCV 78 RR 59-76
ALP 297 RR 5-160
AST 56 RR 16-55
ALT 79 RR 18-121
GGT 4 RR 0-13

I thought the ALP result was interesting with respect to the Cushing's theory. Vet said it isn't really quite high enough, but she also mentioned cirrhosis which make zero sense to me with a GGT/ALT low and AST just over the reference range. I'm thinking maybe of doing a LDDS but am not sure whether this really conforms to the sort of profile of Cushing's.

Mark

[labblab]

Hi Mark, and welcome to you and Kiwi. I’m afraid I have only a moment to post right now, but I wanted to quickly ask you to please edit your info so as to include the normal reference range for each of those lab values. Thanks so much, and I’ll look forward to talking with you more very soon!

Marianne

[Mark4124]

Done, abbreviated RR no reference range stated on the specific gravity.

[Harley PoMMom]

Hi Mark,

Welcome to you and Kiwi from me as well! I have no experience with diabetes but we do have a sister forum that deals with canine diabetes so I'm including a link to that forum: http://www.k9diabetes.com/forum/ If you haven't joined their forum I strongly urge you to as they are a wonderful group of people that are so very knowledgeable about canine diabetes, and in this way you'll have the best of both worlds.

Lori

[Mark4124]

Thanks and yes, I am on there... was fairly active when he was first diagnosed, stepped away for a time, but now back as things are getting a bit interesting again.

[Squirt's Mom]

Hi Mark,

Welcome to you and Kiwi!

You said -
Vet isn't crazy about my theory and wants to do ultrasounds and a bunch of other expensive tests that I don't think are particularly indicated given what we have found thus far.

First, I agree with your vet. I don't see anything that says Cushing's with the possible exception of the increased difficulty in controlling the glucose. HOWEVER, that could be related to the diabetes very easily. ;) It is hard for us to accept aging in our babies but a 12 yr old pup is in the mid 60's in human years so you can certainly expect to see conformation changes. Trust me on that. ;):D:o

Second, and MOST important is the latter portion of your statement saying you don't see the need for testing. Testing for Cushing's is CRUCIAL...not optional; never, ever optional. Canine Cushing's is one of, if not THE, most difficult canine condition to correctly diagnose. It is as much a process of ruling out as ruling in. The fact that Kiwi already has a serious endocrine disease means that testing is that much more important...and in depth testing to be sure false positives are not being returned because of the diabetes. Diabetes can and does skew Cushing's tests....as can any illness. This is one thing that makes this disease so difficult to diagnose - there are no sure tests, none are 100% accurate, all can be skewed for many reasons. For another, Cushing's mimics other diseases, diabetes included. Hence the ruling out process. So if I were you I would focus on the glucose for now and see if changes in insulin, diet, etc. might not turn things around. If Kiwi can be spared the extra stress of frequent testing not to mention powerful drugs then do all you can to spare her.

Hugs,
Leslie

[Mark4124]

No, no... you are misunderstanding. I don't believe that Kiwi's X-ray and other chemistry justifies a ultrasound and I disagree with the vet that Fructosamine test is going to tell me anymore about his DM than I already know. I certainly think it is critical he be tested for Cushing's before going down that road. I have put in for urine cortisol / creatine as next step. Maybe we can quickly rule out, I'll report back when resulted.

[Squirt's Mom]

ahhh good! Glad to know I was off base! We have seen some real horror stories when vets thought it was just fine to start treatment because the ALP was high and they are supposed to be the professionals. So for a parent just starting down the cush path to think along those same lines is an easy thing to have happen. I can take a breath now. :)

[Mark4124]

Urine Cortisol 16.4
Urine Creatinine 126.2
Ratio 41

Interpretation >= 34 Possible Hyperadrencorticism

I'm curious as you what you all think of this result. Interesting also in light of the ALP and also the difficulty controlling his sugar. He does drink alot and gets hot easily, always has, but then he is also a diabetic.

As per next steps... what are the advantages/disadvantages of the ACTH stim test v the LDDS?

Thanks,

Mark

[labblab]

Hi again, Mark — I’m sorry it took me so long to get back here!

Anyway, in response to your question, the LDDS is generally considered the “gold standard” for Cushing’s diagnosis. However, one big caveat is that it is more vulnerable than is the ACTH in returning “false positives” in dogs who are suffering bodily stress from nonadrenal conditions. For this reason, the ACTH is often recommended for dogs who have concurrent physical issues. In your case, I’d opt for the ACTH.

Also, since you’ve been active on the diabetes forum, folks over there may have already provided this link to you. But I’ll add it here, as well. It’s a blog column authored by Dr. Mark Peterson that discusses the challenges involved in the dual diagnosis of Cushing’s in addition to diabetes. As you’ll see, he places a fair amount of weight upon the presence or absence of skin/coat problems. He also provides his own definition of insulin resistance. So if you’ve not see this already, take a look for the sake of interest.

https://endocrinevet.blogspot.com/2012/01/q-diagnosing-cushings-disease-in-dogs.html?utm_source=dlvr.it&utm_medium=facebook

And definitely let us know how you decide to proceed.

Marianne

[Mark4124]

Thank you. I have noted improvement since he started on Augmentin, we believed he may have a sub-acute infection, but he still is very vulnerable to any additional calories and needs a pretty big amount of insulin. So it is tough here, on one hand it looks kinda iffy that he has Cushing's on the other hand there are some indicators. With respect the question of pituitary tumor v. adrenal hyperadrenocortism, does ACTH determine that? What is the difference in treatment/protocol pituitary v adrenal origin?

Mark

[labblab]

Unfortunately, ACTH results do not differentiate between the two types. Another drawback is that a significant number of dogs with adrenal Cushing’s will register “false negatives” on the test. However, it does a relatively better job of correctly identifying the disease in dogs with pituitary tumors, and PDH is the more common of the two types of Cushing’s. The risk of returning false negatives is the reason why the LDDS is generally preferred in instances where no other known diseases are at play. But in deciding between the two tests, you’re basically weighing relative risks: will it be more damaging to miss making the Cushing’s diagnosis in a dog who truly has the disease, or will it be more damaging to mistakenly diagnose (and begin treating) a dog who doesn’t have Cushing’s and is instead suffering from a different ailment altogether. I am not a vet, but my personal preference for a dog of my own would be to first start with the ACTH if I know another illness is present. If the dog tests positive, then I’d find some reassurance in knowing that the positive result came on the test that is more specific to Cushing’s.

As far as then differentiating between the two types, you’d need to proceed to additional blood testing or an abdominal ultrasound in order to actually visualize the adrenal glands. Most pituitary tumors are benign; adrenal tumors can be either benign or cancerous. Also, adrenal tumors can become life-threatening if they invade nearby critical blood vessels. If a dog is a good surgical candidate, surgery to remove adrenal tumors has the potential to offer a complete cure. The surgery is risky and very expensive, however. If surgery is not an option, Cushing’s symptoms are managed in the same manner as are those from pituitary Cushing’s: via medication.

So that’s kind of a mini-crash course on the difference between the tests and the types of tumors ;-).

Marianne

[Mark4124]

Kiwi had his ACTH today.

Baseline <0.5 ug/dl
Post Synthetic ACTH - 25.8 ug/dl

Vet felt, particularly in light of his insulin resistance, that it was pretty case closed that he has Cushing's. She also agreed with me that it probably doesn't make any difference whether the origin is pituitary or adrenal and it would be best to simply begin treatment. She started him today at 30mg trilsostane. We'll see how things go. For as long as I can remember he drank a hell of a lot and was heat intolerant, even before he had diabetes. I'm feeling this diagnosis explains a lot about him and I'm hopeful that treatment resolves some of his outstanding issues and insulin resistance. Could just be that it was cooler tonight but he went for a hell of a walk 3hrs after his first dose. So far so good.

Mark and Kiwi

[Harley PoMMom]

Hmmm, that baseline level is low, was Kiwi pretty laid back when the blood draw was taken? Does he still weigh 26 lbs? Is Kiwi getting his Trilostane with a meal so that it is properly absorbed? Has an appointment been scheduled for that 10-14 day recheck?

[lulusmom]

Hi Mark. I only have a moment but would like to ask a few questions. Did your vet make sure Kiwi's blood glucose was well below 400 mg/dL before administering the uc:cr and acth stimulation test? This is very important because if bg is above 400 mg/dL both tests can yield a false positive results? One third of Mini Schnauzers have hypertriglyceridemia/hyperlipidemia. Since these can make it difficult to regulate bg, did your vet check Kiwi's triglycerides to rule this out as a possible cause? I've seen more than a few Mini Schnauzers, with and without diabetes, misdiagnosed with cushing's and since Kiwi has no skin and coat issues, I have concerns about the validity of the diagnosis. If you used the link Marianne provided to Dr. Peterson's Q & A website for vets, you will see that the dog being discussed is a Schnoodle. Much like Kiwi that dog was receiving insulin doses much below that which is usually defined as being insulin resistant. Most specialists set that threshold at 2.2 U/kg per injection and Kiwi is getting only 1 U/kg per injection so you have a long way to go before most experienced vets would be looking at insulin resistance. It is possible that Kiwi has cushing's but without further information from you, I would be hesitant to start treatment. If the diagnosis is correct, you need to know that cushdogs with concurrent diabetes should be on twice daily dosing of Vetoryl. The reason for this is that Vetoryl has a short half life, meaning it's effects start to wear off after 8 to 10 hours. By dosing every 12 hours, you are effectively controlling cortisol throughout the day, eliminating the possibility of spikes in bg. It is also recommended that dogs start on a dose of 1 mg/lb so if it were me, I would personally talk to the vet about changing the dosing to 15 mg am and pm. I will look forward to your reply.

Glynda

[Mark4124]

Yes, he was below 400, in fact he was 147mg/dl on UC/CR and likely similar on ACTH. He was also quite chill on test. I like the suggestion of twice daily dosing. He has not had his triglycerides check perhaps we can do that on followup ACTH test in 30d. I think we need to see how he reacts to the trilostane at this point. Over the next few weeks. I will let you know.

[Mark4124]

Things were going rather well til Thursday. His need to drink has decreased, particularly at night, and he has had no peeing in the middle of the night crisises. I also was able to reduce his insulin by a small amount, 12iu to 10iu. However Thursday my friend who was taking care of him said he was disoriented and didn't even get up initially when he returned from work. I assumed it was a sharp case of hypoglycemia... which happened to me once a few yrs ago. He did recover from this incident, but he is still a little off. He seems a bit weak in his hind legs and while more alert still a little slightly confused. He will be having his follow up tomorrow morning so I will have them add CBC and Complete Metabolic panel to his ACTH Stim.

[Mark4124]

So he had his follow up ACTH Stim test and his pre was 0.6 and his post was 2.5. The vet wants to lower the dose. Technically the RX insert says that one should continue that the present dose at 1.45-5.4ug/dl cortisol, but this vet isn't comfortable with a 2.5ug/dl. I'm actually fine with this for two reasons:

1. His sugars are more in control when he takes his pill. Currently at 30mg 2x a day. Going to 10mg 2x a day would make for better control than the 1x daily dosing.
2. He is arthritic and I think his arthritis has been worse since initiating the Vetoryl which would be consistent with having less anti-inflammatory cortisol in his system.
3. He did seem to have a worrisome hypoglycemic incident while a friend was caring for him while traveling, I'd like to avoid this happening again and a lower dose may help in this regard as well.

So off to 10mg 2x a day.

[Squirt's Mom]

geez....2.5 ug/dl is PERFECT so the vet is way off base here wanting to up the dose based on the post #. They are also off base wanting to raise the dose in the first 30 days because the starting dose will very often continue to lower the cortisol for at least 30 days. Dechra says NOT to raise the dose in those first 30 days as a result. So your instincts are spot on - stay on the same dose for now....and watch closely for any signs of the cortisol going too low.

[labblab]

Hmmmmm, just to clarify, your vet is wanting to lower the trilostane dose from 30 mg. once daily to 10 mg. twice daily? If so, I agree that changing the dosing in this way seems to be reasonable. First of all, as you’ve already noted, twice daily dosing is definitely preferred in the treatment of diabetic dogs.

Secondly, even though it’s typically the post-ACTH value that is of prime importance when evaluating appropriateness of dose, your dog’s baseline resting cortisol level is awfully low. I notice that the baseline was also quite low at the time of the diagnostic ACTH, too, and I honestly don’t quite know what to make of that. But if the resting cortisol consistently runs really low, then I agree with you that lessening the added suppressive effect of the trilostane might ease your dog’s increased arthritic discomfort.

So all in all, I think the new dosing regimen is certainly worth a try. Do let us know how things go.

Marianne

[Mark4124]

Thanks... and yes, we are going down from 30mg once a day to 10mg 2x a day for a total of 20mg.

[Mark4124]

FYI... wanted to update. Kiwi is still kicking butt. He is old, no doubt about it, he will be 13 in March, but he is still spirited and active. He has lost more weight and has some occasional issues with arthritis, but still is very eager to go for a several mile walk every day. I'll have to take him back sometime soon and get his cortisol level check I suppose. I am interested in Anipryl, not just for its Cushings effect but also for its longevity and cognitive benefits. I see some folks out there with some experience with the substance. Has anyone used it in conjunction at a low dose with Vetroyl?

Mark

[Squirt's Mom]

My Squirt used it with Lysodren. Dr. Jack Oliver with the University of Tennessee in Knoxville told me it would be fine to use them together. HOWEVER, Lysodren and Vetoryl do not work the same way. Lyso works ONLY on the adrenal glands while Vetoryl works on the HPA (Hypothalamus, Pituitary, Adrenal) axis, or loop. Many many things are controlled along that loop so I would want to talk to Dechra about using the two of them together. You can reach Dechra here -

Telephone: (866) 933-2472
E-mail: support@dechra.com

[Harley PoMMom]

According to Dr. Mark Peterson, who is a renown veterinarian that specializes in endocrinology and frequently contributes to Dechra's online continuing education for veterinarians, Anipryl can be used concurrently with Trilostane; here's an excerpt from Dr. Peterson's blog:
If you believe that Rigby has canine cognitive dysfunction, you can certainly use the drug selegiline hydrochloride, also known as L-deprenyl (veterinary trade name, Anipryl) along with the trilostane that the dog's already getting. https://endocrinevet.blogspot.com/2011/04/q-pacing-and-circling-in-cushings-dog.html

So glad to hear that Kiwi is doing so well! You're doing a wonderful job!!!

Lori

[jrepac]

FYI... wanted to update. Kiwi is still kicking butt. He is old, no doubt about it, he will be 13 in March, but he is still spirited and active. He has lost more weight and has some occasional issues with arthritis, but still is very eager to go for a several mile walk every day. I'll have to take him back sometime soon and get his cortisol level check I suppose. I am interested in Anipryl, not just for its Cushings effect but also for its longevity and cognitive benefits. I see some folks out there with some experience with the substance. Has anyone used it in conjunction at a low dose with Vetroyl?

Mark

I used it several years back before Vetoryl became available here in the US...it helped w/some of the more "out there" behaviors, which I assumed to be Cushings (as she was diagnosed) but are also common w/doggie dementia. Such as nighttime wandering, restlessness, barking, etc. Worked very well for us, and took the edge of the hunger and drinking urges. It's one of those hit or miss drugs...works for some, not for others, from what I have heard.

[Mark4124]

Maybe this is a dumb question, maybe it has already been asked before. If that is the case forgive me, but interesting scenario I am facing with my dog Kiwi.

1. He is pretty old... turned 14 in March
2. He is also diabetic and at times has been a bit difficult to control

I suspected Cushing's a few years ago because of this diabetic control issues as well as his thirst. When I first had ACTH stim done his baseline was 0.5 and post 25.8. We started vetoryl at 30mg once daily. I found pretty quickly he seemed to be more arthritic. I theorized that his dose was too high and without so much cortisol he was having more joint pain. Also I was concerned that he should have twice daily dosing as he is diabetic and it might make for more consistent control. We moved to 10mg 2x per day and his pre was similar but post ran 2.8-5ish. We continued with this dose for the next two years.

More recently I became aware of Selegiline and decided to try that for its general anti-aging effect. I only give him 5mg in the morning, but this detail I think is important because it can have a pituitary Cushings effect.

He was on both meds for roughly 6m and then in March had anoerxia and vomiting. I was concerned he had cancer given his age, but a whole battery of tests and nothing found. I started to suspect the vetoryl may be at issue. We did another ACTH stim test and he was 0.7 pre 1.7 post... I cut his vetoryl in half and low and he started eating again and was fine.

Come to last weekend. I had dropped him off at his dog sitter a few days earlier as I was heading to the Black Hills/Badlands for a little Memorial Day vacation. Wake up one morning with an urgent message from the dogsitter that he had a 3min siezure and they rushed him to the emergency vet clinic. His electrolytes were low, not severely, but they were low. His blood sugar was high which was odd as he apparently wasn't eating well. They provided supportive treatement, prescribed some antibiotics in case he had a subacute UTI as diabetics sometimes can, and generally got very interested in the shiny object of his blood sugar levels. I had them release him the next night and he was fine for the dog sitter and since I picked him up again Wed afternoon he has been great. I have not given him any vetoryl at all since and his blood sugar levels have actually been better than ever and he is eating robustly.

So of course I need another ACTH stim test after a time. I understand that. But I'm somewhat wondering if Cushing's ever resolves after years of vetoryl treatment? Or has it been so blunted that maybe the Selegiline alone, low dose that it might be, is sufficent?

[labblab]

Hi Mark, welcome back to you and Kiwi! You’ll see that I’ve gone ahead and merged your new post into your original thread. This way we’ll be able to keep Kiwi’s entire treatment history consolidated in one place ;-).

I’m sure sorry for the scare last weekend, and so relieved to hear that he’s doing much better again. Your question is not dumb, at all, but I guess that time will tell as far as an answer in Kiwi’s case. We do know that it’s possible for Vetoryl to make permanent changes in adrenal function. It happens rarely, but on occasion we’ve had members who found that continued use of Vetoryl ended up oversuppressing adrenal function such that treatment was discontinued, sometimes for good. In some cases, the dogs end up needing actual supplementation of adrenal hormones in order to make up for the oversuppression. In other cases, the dogs don’t require supplementation but also never need to resume Vetotyl. So maybe Kiwi is a lucky boy who falls in that latter category.

I don’t think the selegiline would be responsible for the lower cortisol reading, because my (feeble) understanding is that selegiline’s effect is not actually reflected in measured cortisol levels. However, my knowledge about selegiline is sadly minimal. It does seem possible to me, though, that both effects may be possible: the selegiline may be helping to make him feel more comfortable even as the Vetoryl may have produced a longterm effect on his cortisol level. Either way, I think it’s a great gift that he’s doing better. And under these circumstances, I definitely wouldn’t be rushing back to add in Vetoryl again now, if ever.

Please do keep us updated,
Marianne

[Mark4124]

Thank you... I will keep an eye on things and do another ACTH stim test in a few weeks.

Mark

[Mark4124]

Well, based on ACTH stim test I guess I'm done here:


Date Lab Test Lab Results Evaluation Lab Range Location
06/09/20 CORTISOL SAMPLE 1 2.2 ug/dL 1.000 - 5.000 ug/dL Rockwall
06/09/20 CORTISOL SAMPLE 2 8.6 ug/dL 8.000 - 17.000 ug/dL Rockwall

[labblab]

Hi again, Mark! Honestly, I think only time will tell as far as ever needing to resume Cushing’s treatment (and that’s not because I’m trying to hold you captive here :rolleyes:). As long as Kiwi is comfortable and essentially symptom-free, that post-ACTH reading of 8.6 is good. However, the question will be whether or not his cortisol production plateaus at that level, or whether it continues to rise over time.

The diagnostic normal range that the lab has given you is applicable when the purpose of the test is to determine whether a dog has Cushing’s. For dogs known to be suffering from Cushing’s who are under treatment, the desired range is much lower: approx. 1.5 - 9.2. So Kiwi remains within that range for now — we don’t know whether he’ll ever leave it once again. His cortisol now is higher than it was when you tested back in March, and that’s a good thing since it was too low for him at that time. We don’t yet know for certain whether or not it will ever start increasing more rapidly again. However, especially given his age, as long as he’s doing well and doesn’t start exhibiting Cushing’s symptoms once again, I think you guys are good to go. Enjoy your time together, and especially this vacation from treatment for however long it may last — hopefully forever!!

We’ll always be here should you need us again, though ;-). All best wishes to you and Kiwi, today and every day.

Marianne

[Mark4124]

Sadly things took a bad turn...

I noticed after walks he seemed pretty tired and in the evening a bit uncomfortable. I took him to the vet on Thursday for recheck of his UTI and stones. His UTI seemed to be resolved or resolving and the stones were lesss numerous. We kept him on Clavamox nonetheless for another 10d in case the stones released more bacteria or the infection wasn't 100% subdued. He didn't eat as much on Thursday evening, even less so on Friday morning and seemed a bit lethargic. Friday evening he wouldn't eat but a little kibble. He threw up in the early morning and appeared to be in pain on Saturday. I took him to the ER vet hospital and he was diagnosed with pancreatitis. The hope was for pain meds and fluids and pancreas to heal itself (interestingly his white count was not high, almost as though his immune system wasn't really working). But unfortunately by Sunday morning there was septic fluid about his organs. I took him home and he passed away peacefully in the afternoon. It is really, really hard. I think so much the harder as with his diabetes and Cushing's he required lots of care, he was my world. Despite all that though he survived long and was stunningly active until the very end.

Thank you for your advice over time.
Kiwi - male Schnauzer, 2yrs Cushings, 4yrs diabetes, 14yrs 3m on passing on 6/21/2020

[Joan2517]

I'm so sorry for your loss of dear, sweet Kiwi. Many hugs to you at this difficult time.

[labblab]

Oh Mark! I’m so sorry, too, for your loss. Just when we were hoping that things had settled down a bit, and now this sad news. You have been such a wonderful dad and have taken such good care of your boy. Even with his illnesses, you granted him a long and joyful life. I so understand what you mean about the sudden and special emptiness in your own life right now, though, after having been so watchful and so tender in your care for him. Suddenly there is no longer a schedule or purpose to the hours as they tick by. And no devoted companion by your side. A loss like this cuts so deeply, and is so very hard indeed.

We hope it may bring you at least a little comfort to know that Kiwi has now been added to our special memorial thread of honor:

https://www.k9cushings.com/forum/showthread.php?9294-Remembering-All-Who-Have-Left-Us-(2020)

And please know that we’ll welcome you back at any time if you want to talk more about what has happened or how you are doing. Again, I’m so deeply sorry, but very grateful that you returned to let us know.

Warm thoughts always, to you yourself, and in loving memory of your brave boy.
Marianne

[Squirt's Mom]

Dear Mark,

I am so sorry to learn about your precious Kiwi. No matter the circumstances we are never ready for that day to come when our babies must leave us. It is my firm belief that we will see them again when our jobs here are done. Until that day, we will carry the pain of their physical absence along with the ever-lasting love we shared with them. Please know we are here if you need to talk...we DO understand.

My deepest sympathies,
Leslie


A Bridge Called Love

It takes us back to brighter years,
to happier sunlit days
and to precious moments
that will be with us always.
And these fond recollections
are treasured in the heart
to bring us always close to those
from whom we had to part.

There is a bridge of memories
from earth to Heaven above...
It keeps our dear ones near us

It's the bridge that we call love.

Author Unknown