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jeskel
05-11-2018, 07:20 PM
Hi Everyone,

I first posted over on K9 Diabetes, but I am leaning towards Cushing's being the key to determining whether Diabetes plays into symptoms. Kelsey is 13.5 and a Vizsla. She has had Cushing's symptoms for a long time (since age of 7), but they have been relatively stable, so they opted against doing formal diagnostics and treating, but she has been treated for Thyroid with Levothyroxine and has been pretty stable on that since 2015.

Her "crash" came about in early March 2018. Started with vomiting, diarrhea, 20 pound weight loss in a week, no longer eating, and was drinking water like no tomorrow with accidents to go along with the excess water intake...she was brought to the clinical for full blood tests that showed most notably a spike in glucose (over 680 mg/dl). Her BUN was elevated in the mid-30's mg/dl, and her ALK PHOS was reading out at 1649U/L. PHOS and Potassium were only slightly elevated. There was nothing considerably concerning on her hematology panel. Her UA showed ketones (15mg/dL) and Glucose (1000mg/dl). She was hospitalized for two days with initiation of long acting insulin along with bolus insulin to get her glucose back down and get her back to eating again.

Since the initial hospitalization, I have been struggling with getting a glucose curve anywhere near normal range, and after 3 consecutive insulin increases, ACTH and Low Dex Tests were done. As with everything, her results were borderline, but that in combination with years of clinical symptoms lead to the decision to try trilostane treatment (30mg morning / 10mg evening) to see if that would give us any improvement on glucose levels. Her results for her Low Dose Dex and ACTH tests are below, but I'm looking for feedback on anyone else with a similarly complex case on next steps...we are two months into this and while she is doing much better based on observation, her glucose is still severely out of control. I feel like her ACTH results are telling us to reduce her trilostane dose to avoid pushing her to Addison's, but initiating trilostane yielded the first glucose reading down in the 100's! Her weight is stable (within 2 pounds of her hospitalization weight)...

Diagnostic Low Dose Dex:
Cortisol Pre-Dex 2.1ug/dl
Cortisol 4 Hour Post-Dex 0.8ug/dl
Cortisol 8 Hour Post-Dex 1.5ug/dl

Diagnostic ACTH
Cortisol Pre-ACTH 2.4ug/dl
Cortisol Post-ACTH 21.3ug/dl

Post Trilostane ACTH
Cortisol Pre-ACTH 0.9ug/dl
Cortisol Post-ACTH 5.8ug/dl

Post Trilostane ACTH Re-Test
Cortisol Pre-ACTH <0.2ug/dl
Cortisol Post-ACTH 7.0ug/dl

Posts from K9 Diabetes for Reference:

I am struggling with insulin regulation in a newly diagnosed canine diabetic. Diagnosis was in March, insulin doses (U-100) started at 12 units 2x/day dosing, now up to 19 units 2x/day. I am doing curve testing using alpha track 2 at home, but I am seeing insulin duration of action as short as 2-3 hours, with the longest being 5 hours post dose before glucose spikes again.

When we first started out post hospitalization, curve started at mid 600 (pre-dose / 8 am), and dropped to mid 300 by noon, then spiked back to values between mid 500's and 700 for remainder of day. With the first dose increase, the curve started at mid 400 pre-dose, dropped to upper 300 at 10 am, and started increasing at noon with values ranging from mid 400's to mid 500's for remainder of day. With second dose increase, the curve started at upper 300 pre-dose, dropped to mid 200 at 10 am, and started increasing at noon with values ranging from mid 300's to mid 500's for remainder of day. Finally, the most recent increase resulted in 10-noon values that were in the 100's (most stable and favorable low I have seen), increasing to over 200 at 1 pm, and then spiking to 400's, and finally over 700 by the final read (just prior to evening insulin dose).

It seems we are making progress, but the glucose readings seems to be extremely dynamic and the insulin only seems to sustain a response for 3-4 hours at the most. I am under the impression the duration of action should be longer than 3-4 hours on 2x/day dosing. If the most recent numbers indicate we are in the 100's, why is the insulin wearing off and resulting in extremely high numbers the rest of the day?

Dog (13yo / 50+lbs) is being treated for thyroid (long term stable) and Cushing's (started treating more recently because of insulin resistance / symptomatic for some time). Being fed glycobalance by prescription. Vet confirmed earlier curves were not Somogyi as low reads were still extremely high. Is anyone else seeing insulin wearing off this quickly on such a consistent basis? If the goal is to maintain read between 100-200, but we are seeing a low that will now dictate holding dosing to avoid hypoglycemia, but still seeing highs in the 4-700's, it doesn't seem like we are really controlling the diabetes at all.

I am trying to be patient, but I don't want to continue putting my dog through this if the long term prognosis is more of the same. Symptoms have improved substantially overall since initial hospitalization, and quality of life seems to be decent most of the day / night, but I want to get things leveled out more.

--Thank you for your reply. Kelsey is a Vizsla. Breed has certainly crossed my mind as Vizsla's are extremely high energy / high metabolism. My initial concern after her first curve was that the dose was too high, but she is currently at 52 lbs and she was started at 12 units BID. I monitored her very closely for any signs of hypoglycemia when we started, but her levels were only dropping into the mid 300's 4 hours post dose before going back up. Regarding her hypothyroidism...she has been stable on the same dose of levothyroxine for several years. It was diagnosed with a full thyroid panel initially, and we either do full panel or T4 re-checks every 6 months. Also notable: we did a full abdominal ultrasound to rule out presence of sizable tumor involvement, and there was nothing significantly abnormal with her kidney's or adrenal glands. She also had a full set of high res x-rays for orthopedic purposes taken just prior to her diabetic "crash", and there were no abnormalities with organs or soft tissue visible noted there either.

The Cushing's treatment was just introduced, and that may be why we are seeing her first 5-6 hour numbers finally drop into a normal range (I am in the process of verifying the most recent results from yesterday today, and so far the numbers are spot on). We are doing a follow-up ACTH stim to see where her Cortisol levels are at based on her initial dosing soon. My hope is that the trilostane dosing is either spot on or only in need of one more dose increase, and that regulating her Cortisol will finally be the catalyst to break the insulin duration of action issue. I fully expect to reduce her insulin if we end up increasing her trilostane based on her ACTH re-check.


Thank you in advance for any feedback!

labblab
05-11-2018, 09:16 PM
Hello and welcome to you and your girl! I’ve taken a look at your k9diabetes thread, and thankfully it looks as though the good folks over there are offering valuable guidance re: the insulin issues. But yes indeed, you surely are dealing with some complicated issues.

In trying to sort things out, a few questions come to my mind. First, can you give us the dates associated with the Cushing’s tests (both the diagnostic and monitoring results)? Also, can you tell us exactly when you started on the trilostane treatment?

Lastly, I’m curious as to whether your girl’s initial thyroid testing pointed towards primary hypothyroidism, or whether the low thyroid instead appeared to be secondary to some other condition (such as the possibility of undiagnosed Cushing’s).

The big difference between her monitoring pre- and post-ACTH cortisol levels does seem quite puzzling. The pre levels are decidedly low, but the post levels could theoretically come down even more. So there are definitely some big question marks here. For the moment, however, I’ll be content to extend our welcome to you, and await this additional info before speculating more as to what may be going on.

Marianne

jeskel
05-13-2018, 12:00 AM
Hello and welcome to you and your girl! I’ve taken a look at your k9diabetes thread, and thankfully it looks as though the good folks over there are offering valuable guidance re: the insulin issues. But yes indeed, you surely are dealing with some complicated issues.

In trying to sort things out, a few questions come to my mind. First, can you give us the dates associated with the Cushing’s tests (both the diagnostic and monitoring results)? Also, can you tell us exactly when you started on the trilostane treatment?

Lastly, I’m curious as to whether your girl’s initial thyroid testing pointed towards primary hypothyroidism, or whether the low thyroid instead appeared to be secondary to some other condition (such as the possibility of undiagnosed Cushing’s).

The big difference between her monitoring pre- and post-ACTH cortisol levels does seem quite puzzling. The pre levels are decidedly low, but the post levels could theoretically come down even more. So there are definitely some big question marks here. For the moment, however, I’ll be content to extend our welcome to you, and await this additional info before speculating more as to what may be going on.

Marianne

Hi Marianne,

Her diagnostic ACTH was on 14Apr, and the Monitoring ACTH's were done 05May and 10May. Trilostane started 16Apr. Regarding her Thyroid, I am not ruling anything out at this point. It is certainly a possibility given the close symptom profile between the two conditions. She was actually exhibiting what was posited as Cushing's symptoms as early as 2011. I do recall many of the symptoms seems to continue even though the lab results were considered to be stable clinically. Her levothyroxine dose has never changed. Her T4 was re-checked on 09Apr and is stable, so I don't see this as playing into metabolism of insulin...

I agree that the pre- and post-ACTH results are confusing. She was extremely stressed for the run on 10May when the pre- dropped even further. Her post-ACTH results are actually pretty good, but the concern will be the pre-ACTH. We are looking at compounding her dose at 20mg, so she has the same dose morning and evening. I am leaning towards giving that a chance and doing a re-check before changing her total daily dose because her hair has started re-growing in several shaved areas from the last couple months. That was a big indicator that the trilostane is having an immediate effect. I will find out what the veterinary opinion is on this by Monday. We have an amazing vet, and she is working closely with me and consulting with an endocrine specialist, but this case is really tangled!

~Jackie

labblab
05-13-2018, 09:28 AM
Hi again, Jackie, and thanks so much for this additional info. I apologize that time is short for me this morning so I’m not able to write as lengthy a reply as I’d wish. But given Kelsey’s perplexing monitoring results, one thought that occurs to me is the possibility that she might be a candidate for an alternative monitoring protocol: testing resting cortisol immediately before the trilostane is dosed. I will include below a reply that one of our staffers recently posted for another member. Most general vets in the U.S. are probably unaware of this protocol, but most internal medicine specialists have likely been notified. So this may be something that your endocrine specialist has heard about, and might consider for Kelsey. The two pieces of this protocol that seem of value to me in her case are the increased reliance on observable changes, and also my curiosity as to what her cortisol level looks like before dosing occurs. Since she’s getting the trilostane twice daily (which indeed is recommended for diabetics), there may not be enough time between doses for much of a cortisol rebound to occur. But still, it might be of interest to take a pre-pill testing, at least on one occasion. The belief among the European vets who have been using this protocol is that it provides a monitoring method that is superior to sole reliance upon the ACTH. Plus, it’s cheaper! Anyway, here’s the related info, and I’ll be back again myself either later today or tomorrow.


Here ya go. This page from the Dechra website has videos of Professor Ian Ramsey who explains this new monitoring tool in detail. This will make it very easy for your vet to follow the protocol. By the way, this monitoring protocol has been used in the UK for over two years as well in some European countries. Dechra will eventually publish this information to vets in the U.S. however, their hands are tied until the FDA approves this change. That doesn't mean U.S. vets can't start utilizing it now. Hopefully your vet will be open to working with you on this. It's an exciting development that will make treating canine cushing's a lot less expensive. That could mean the difference for a dog whose owner simply cannot afford the cost of acth stimulation tests.

https://www.dechra.co.uk/therapy-areas/companion-animal/endocrinology/canine-hyperadrenocorticism/vetoryl-monitoring-1

Marianne

jeskel
05-15-2018, 08:55 AM
Hi again, Jackie, and thanks so much for this additional info. I apologize that time is short for me this morning so I’m not able to write as lengthy a reply as I’d wish. But given Kelsey’s perplexing monitoring results, one thought that occurs to me is the possibility that she might be a candidate for an alternative monitoring protocol: testing resting cortisol immediately before the trilostane is dosed. I will include below a reply that one of our staffers recently posted for another member. Most general vets in the U.S. are probably unaware of this protocol, but most internal medicine specialists have likely been notified. So this may be something that your endocrine specialist has heard about, and might consider for Kelsey. The two pieces of this protocol that seem of value to me in her case are the increased reliance on observable changes, and also my curiosity as to what her cortisol level looks like before dosing occurs. Since she’s getting the trilostane twice daily (which indeed is recommended for diabetics), there may not be enough time between doses for much of a cortisol rebound to occur. But still, it might be of interest to take a pre-pill testing, at least on one occasion. The belief among the European vets who have been using this protocol is that it provides a monitoring method that is superior to sole reliance upon the ACTH. Plus, it’s cheaper! Anyway, here’s the related info, and I’ll be back again myself either later today or tomorrow.



Marianne

Hi Marianne,

Thank you so much. This is extremely helpful. I am in the process of obtaining some answers on this protocol for the vet so we can give it a try. We are getting our compounded trilostane this week as well, and I am eager to see if that will help smooth out her glucose curves as well!

Best Regards,

Jackie (and Kelsey)

DosCanid
05-15-2018, 11:11 AM
My heart breaks reading this thread, but I can see you have the strong will to fight for your dear Kelsey. Unfortunately, I have just started my Cushing's journey with my 9-year-old so I lack the knowledge to share with you, but I'm definitely waiting on all your posts and updates.

My thoughts are with you and your dear Kelsey! :o

jeskel
06-05-2018, 09:21 AM
Hi Marianne,

Thank you so much. This is extremely helpful. I am in the process of obtaining some answers on this protocol for the vet so we can give it a try. We are getting our compounded trilostane this week as well, and I am eager to see if that will help smooth out her glucose curves as well!

Best Regards,

Jackie (and Kelsey)

Hello Everyone,

Just a quick update on Cushing's: Kelsey has successfully switched over to her 20mg (40mg total daily dose) trilostane, and had her first Pre-Dose Cortisol check following the new Dechra European Guideline. Her cortisol came in at 2.1 ug/dl (at lower end, but within normal limits). According to Dechra, her number, along with absence of clinical symptoms of Addison's means she stays at her current dose.

I posted an extensive update on Kelsey's diabetes on K9 Diabetes...in short, her glucose numbers are still high, but she now has a normal curve and the new insulin she is on has improved the duration of decrease in her glucose numbers. It will likely take at least another 4-6 weeks to get her glucose numbers down to where they really need to be, so my plan with regards to her Cushing's is to do monthly Pre-Dose Cortisol checks following the Dechra European Guideline the next few months and then repeat another ACTH Stim at month 3 in tandem with Pre-Dose Check just to make sure we are staying on top of any diabetes management effects on her Cortisol numbers. According to the Dechra European Guideline, she doesn't need to be checked monthly at this time, but she has a lot going on with trying to regulate insulin, so I am leaning towards more monitoring is a good thing for now.

Special thanks to Marianne for the info on the new monitoring protocol! I was pleased with her results, and am happy to see her staying on a consistent dose rather than being dropped down in light of the glucose regulation issues we are attempting to correct. I will post another update after her glucose is where it needs to be. In the meantime, please reach out or post with any questions on her case. I am expecting some of her remaining Cushing's issues to resolve once her diabetes is in check (I.e. Loss of Muscle / abdominal distention) and she can get back to more of a regular appetite and exercise routine again! For now, I am content with her hair re-growth. Every day is a work in progress...

labblab
06-05-2018, 12:26 PM
Thank you so much for this update, and kudos to you and Kelsey on your progress thus far!! I know you still have a ways to go, but I think you’ve made great strides in moving forward under very challenging circumstances.

I’m so glad the new monitoring protocol seems to be working out to your advantage. We are so anxious to get feedback about this from our members. You and Kelsey are among our first pioneers here on the forum, so we are especially grateful to hear about your experiences. We wish you continued good luck, and please do keep those updates coming!

Continuing best wishes,
Marianne

Squirt's Mom
06-05-2018, 01:24 PM
What a great update! I am so glad Kelsey is doing so well! And very glad to hear the new protocol seems to be viable and we are so very thankful to you and Kelsey for sort of paving the way for us. Great job, Mom!