Yukon, American Eskimo - Experience w/ Lignans and Melatonin?

[YukiesMom]

Good Morning,

I have a 13 year old American Eskimo named Yukon and I have to say he has been a very high maintenance dog over his life. He has allergies (beef, grass) in which we had testing done and order serum and have injections. He has also had Invertebral Disk Disease (getting Laser), ate a Chicken Carcase and had 100 bones pulled out of his belly in which he then developed Pancreatitis which became Chronic, and last year I was told that he might have IBD.

His last Pancreatic attack was last August, 2017 and recovered quite well. This winter I noticed he started gaining his normal winter weight but it looked like a little more than usual. Over the last couple months I noticed he was drinking a lot more water and panting a lot.

I took him to the Vet for his Heartworm and Bloodwork on March 25th and the vet said he had high Liver enzymes - ALKP was about 508 and ALT was 155. She advised that I put him on Denamarin and we monitor his liver. For some reason I suggested that maybe we do a Cushing's test because I started walking him over a mile a day and he was not losing the weight and panting a lot. I also took him in for an ultrasound of his liver and she noted it was enlarged, but she could not see any masses.

April 13th we did the Low Dose Dexamethasone test and the following results came through

Pre Dex 3.9 ug/dL
4 Post Dex 0.3 ug/dL
8 Post Dex 1.8 ug/dL

She indicated he has Pituitary Cushings and they begin treating at 1.5 ug. He is 32 pounds and we started him on 10mg of Vetoryl since he is very sensitive to a lot of medications. I started giving him the Meds on Monday, April 16th.

The first day he seemed ok, but the second day within an hour of me giving it to him it seemed like he just totally zoned out and for hours he would walk around in a daze and sleep most of the time. I did notice the panting reduced and the water intake was not as much, but he was by no means perky. I advised the vet after about 4 days that his behavior was a little strange. We went about 6 days and my both myself and my vet contacted Dechra and asked about his symptoms. My vet told me on April 25th to stop the Vetoryl because the company said his body might be used to the high cortisole and the medication might be making it too low. I also took him off the Denamarin.

We went back to the vet on April 21st and had more bloodwork pulled and his Liver Enzymes went up to ALKP 585 and ALT 290. She also confirmed that he had Pancreatitis - his level was 712.

Since then I have been off everything, on May 2nd I brought him back to the vet because he was not acting right - very lethargic. I had her pull more blood and his Liver Enzymes ALKP went up to 923 and ALT rose to 309. She also pulled blood to check his pancreas level and cortisole level and told me that if his cortisole was high we would put him on 5mg of vetoryl right away, even if it wasn't 14 days since he was off the other dosage.

My vet went on vacation and the tests came back so I called and spoke to another vet at the clinic. His pancreas went down from 712 to 538. The cortisole test showed 2.8 and the vet said that normal is between 2-6 so he is on the lower side.

I am very confused now because I don't know if I should put him back on the lower does of Vetoryl. He still has the symptoms of Cushings but in the last 4-5 days he has regained his spunky attitude again. I did put him back on the denamarin for his liver.

Any advise would greatly be appreciated - this is very frustrating. Thank you :-)

[Squirt's Mom]

Good morning and welcome to you and Yukon! :)

My concern is with the validity of the LDDS because it is notorious for giving false positives when another illness is present and pancreatitis most certainly falls into that category. The body, both human and canine, will release extra cortisol in response to stresses - internal and external. If a pup gets very stressed just going to the vet that can skew the Cushing's tests...pancreatitis would definitely skew the results. My own Squirt was diagnosed with Cushing's but as testing proceeded and we did the ultrasound a tumor was found on her spleen. Once that tumor was removed her cortisol returned to normal and remained normal for several years. So that is a lesson I will never forget nor fail to share when I see a pup that tested positive for Cushing's while under stress from some other source.

So having said that, there is no way in you know where I would restart the Vetoryl. The diagnosis for Yukon is very iffy in my mind. There are two drugs used to treat Cushing's - Vetoryl and Lysodren. Vetoryl WILL cause problems if the Cushing's is a misdiagnosis, like my Squirt's was. However, Lysodren will not cause problems - it works ONLY on the adrenal glands so if there is nothing happening with them it does nothing. So I would NOT restart the Vetoryl right now - I would give Yukon time to recover as best he can and then retest.

I'm glad you found us and look forward to learning more as time passes. I am sure others will be along to offer their insights as well.

You need to know that you and Yukon are now part of our little family here now and we will be with you every step of the way on this journey. You and Yukon will never be alone.

Hugs,
Leslie

[Harley PoMMom]

Hi and welcome to you and Yukon!

My oh my your sweet boy has been keeping you on your toes! American Eskimo's are such beautiful dogs with that lovely fur coat! Regarding his cortisol level, was that checked with an ACTH stimulation test, and if so, was the 2.8 (I assume the units of measurement are ug/dl) a post cortisol result? If the 2.8 ug/dl is a post reading and even though he is still presenting symptoms I wouldn't restart the Vetoryl until his cortisol has had time to rise a bit more (since he was off the Vetoryl for 7 days and cortisol was only 2.8 ug/dl) and I would instead try to get his pancreatitis under some kind of control.

Pancreatitis can be a bugger to get an upper hand on, my boy Harley, had chronic pancreatitis and we were never able to get his numbers in the normal range. Is Yukon on a very low fat diet? Also, with pancreatitis it is recommended that dogs be given several small meals throughout the day instead of one big meal.

So, my advice would be to retest pancreas in 3 weeks and if better have a full ACTH stimulation test performed to see where his cortisol levels are and if high than restart the Vetoryl at 5 mg once a day (given with a meal).

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

Lori

[YukiesMom]

Thank you so much for all your feedback Leslie- I have been very leary about putting him back on the Vetoryl. Unfortunately my vet has not really been assisting me in all this since the testing - she recently told me she is not sure which way to go at this point :-(. I feel as though I am recommending things to her and she is going for it.

Yukon is a very stressed dog as it is - afraid of fireworks, thunder, rain, etc. and he trembles every time I bring him to the vet. That's why I was a little surprised that the last blood test where they tested the cortisol level was only 2.8. I think my vet even expected it to be more. I do notice that he pants a ton only at night - I am wondering if because his liver is enlarged and enzymes elevated that is why. I read someone that the liver becomes active between 1-3 am.

I still don't know about all the other symptoms, excessive drinking, eating and weight gain. I was even thinking about going to an Internal Med doctor for a ultrasound of his organs to see if in fact it is something else. I think right now I am going to just keep giving him the Denamarin and see if his pancreas and liver levels go down.

[YukiesMom]

Hi Lori,

Yes he has really kept me on my toes - and I would do anything to keep him happy and healthy because he is in essence my baby. The cortisol level of 2.8 was just a blood draw and they sent it out. Yukon is currently on the Royal Canin Hydrolized Protein Dog Food and Treats. That is all he gets besides occasional green beans - lol. I have been trying to feed him smaller meals throughout the day, especially since he is always so hungry and wants to eat all the time. The funny thing is my husband said he never bugs him for treats all day - he only starts when I get home. I guess maybe I spoil him.

[Harley PoMMom]

The cortisol level of 2.8 was just a blood draw and they sent it out.

The ACTH stimulation test is used to check cortisol levels, a "full" ACTH test consists of 2 blood draws which are a pre and a post reading. It is really important to know if that 2.8 ug/dl is a pre or post blood draw result, could you find that out for us...thanks!


Yukon is currently on the Royal Canin Hydrolized Protein Dog Food and Treats. That is all he gets besides occasional green beans - lol.

It is recommended that a diet with less than 10 percent fat on a dry matter basis to be fed to a dog with pancreatitis, by my calculations his feed is 18% which may irritate that already inflamed pancreas. I've found these articles from the dogaware site to be very informative regarding canine pancreatitis, it also includes a list of dog foods that are low in fat: Healthy Low-Fat Diets for Dogs (http://dogaware.com/articles/wdjlowfatdiets.html) and Pancreatitis in Dogs (http://dogaware.com/articles/wdjpancreatitis.html)


I have been trying to feed him smaller meals throughout the day, especially since he is always so hungry and wants to eat all the time. The funny thing is my husband said he never bugs him for treats all day - he only starts when I get home. I guess maybe I spoil him.

It is so hard not to spoil them, they worm their way into our hearts and we love them deeply. I have no children so my furbabies are my "kids," Yukon is very lucky to have such wonderful parents!

[YukiesMom]

Hi Lori. My vet did a base cortisole blood test. She called yesterday and is baffled at what is going on. I told her his panting is getting worse at night between 1-4 am. I made an appointment with an internal medicine doctor on may 15th. They are going to do an ultrasound of his organs. I am hoping we can get to the bottom of what is going on. Thanks for the articles on the dog food. I was feeding him Nutro sensitive stomach for his entire life (chicken, rice and oatmeal). They changed the formula and it was really hard to find a new dog food with him being allergic to beef and having chronic pancreatitis. He has been on the royal canin hydrolyzed protein over a year and it seemed to be working.

[Harley PoMMom]

It is not uncommon for GP vets to be stumped by complications of endocrine disorders so I personally think it's an excellent idea that you will be consulting with an internal medicine specialist as these vets are highly trained and experienced in all things endocrine.

[molly muffin]

I think going to see the internal medicine specialist is a good idea. Let us know how that goes and what the IMS thinks is going on.

[YukiesMom]

So I went to the internal medicine doctor yesterday and it was a little disappointed. My vet sent him all the records and did a summary page and he didn't even read it. I told him everything going on and he then performed the ultrasound. He indicated in his notes that the ultrasound revealed nonspecific hepatopathy and mild renal remodeling. Said that the former is likely multifactorial, both inflammatory bowel disease (argued based on his elevated folate and history of recurrent diarrhea) and early onset pituitary dependent hyperadrenocorticism (based on normal adrenal glands on the ultrasound and the recent LDDS test) are contributing to the hepatic changes.

He sent out two urine tests - one culture for PUPD and a UCCR to characterize the adrenal glands further. He then wants me to get another ACTH stimulation test from the University of Tennessee. He wants to send it there because he thinks that maybe something else is triggering the Cushings (ie: Hormones, testastorone, etc.)

Has anyone ever heard of other factors that are contributing to the cortisol over producing? He said not to give him the Vetoryl because it is not helping him and that once we find out what it might be we can medicate accordingly.

Now I am even more confused :-(

[labblab]

Under the circumstances, I think your internist’s suggestion to have Yukie’s ACTH analyzed by the University of Tennessee makes sense. Their lab is able to measure the effect of the stimulating agent on a number of adrenal hormones in addition to cortisol. As it turns out, elevations in some of these other hormones can result in many of the same symptoms as are caused by elevated cortisol. Sometimes this occurs even when cortisol levels are normal or only mildly elevated, and therefore treatment other than Vetoryl may be recommended. Since Yukon reacted so poorly to the Vetoryl, this additional information may be useful.

When elevations in other adrenal hormones cause problems, the diagnosis that may be given is “Atypical Cushing’s.” You can read more about this diagnosis here. It can be fairly heavy reading, and unfortunately a lot of question marks yet remain about the cause, significance and treatment of elevated adrenal hormones. But this info may help shed some light on the testing that the internist is suggesting.

http://www.k9cushings.com/forum/showthread.php?198-quot-Atypical-Cushing-s-quot-Congenital-adrenal-hyperplasia-like-syndrome-Hyperestrinism

I do think the results of the ACTH will be useful, especially since this will be the first ACTH for Yukon. In terms of elevated cortisol, the ACTH is less vulnerable to “false positives” than is the LDDS because it is not quite as reactive to the presence of other physical illnesses or stresses. So overall, I think this is a good plan for Yukon.

To me, the only questionable aspect of your internist’s plan is the UCCR if the urine sample was obtained in the office. That test is highly vulnerable to stress so it is generally recommended that the sample be obtained at home when the dog is calm. But perhaps your vet thought, what the heck, let’s go ahead and see how it turns out anyway.

So, in summary, do keep us informed. But I do think the ACTH may be useful.

Marianne

[YukiesMom]

Thank you so much Marianne for the explanation - maybe we will be able to determine what is really going on finally. Also, the UCCR test is being ran from a first morning urine that I collected on his walk when we got up. One thing I have learned is that it is better to bring the urine sample even if they don't use it :D

I will keep you informed of Yukon's travels - thanks again for the information.

[labblab]

Also, the UCCR test is being ran from a first morning urine that I collected on his walk when we got up. One thing I have learned is that it is better to bring the urine sample even if they don't use it :D


Perfect! Then the results from the urine sample will definitely be interesting, too.

Good job, mom!!!

[YukiesMom]

I am trying. This is very complicated. I just wish someone could come to a diagnosis. I have been saying for the last two weeks I want to put him on lignans and melatonin. I have been reading about this venue for atypical cushings.

[YukiesMom]

So I went to the Internal Medicine doctor and he got the results of the urine back and confirmed Yukon displayed cushings. He then suggested a stim test that the university of Tennessee does to measure various levels within the adrenal gland itself. I went to my vet and had the test done and she called me yesterday and said three of the levels were high and confirmed pituitary cushings. She said first recommended treatment is trilostane but because Yukon had problems with it there were a few other possibilities. She is forwarding to the internal medicine doctor to see what he suggests. I feel like it is hopeless because he can't take the trilostane.

[labblab]

Hello again, and thanks very much for this update. It will be a huge help to us, though, if you can get a copy of the exact test results from Tennessee. That way, we can better discuss the different treatment options that may be available, given Yukie’s precise elevations. For instance, there is an alternative drug to trilostane that is named Lysodren. It is very effective at lowering cortisol, and also lowers certain other adrenal hormones as well. So please don’t give up hope — there may yet be a treatment plan that can be very helpful for Yukie. But first we need to see those test results ;-).

Marianne

[YukiesMom]

Hi Marianne,

Here are the test results from the University of Tennessee:

RESULT Normal RESULT Normal
(Baseline) Range** (Post ACTH) Range**
Baseline Post-ACTH

Cortisol ug/dL 3.4 <1.0-5.6 13.4 7.1-15.1
Androstenedione Ng/ml 1.11* 0.05-0.36 6.10* 0.24-2.90
Estradiol pg/ml 77.9* 23.1-65.1 77.9* 23.3-69.4
Progesterone ng/ml <0.20 <0.20 1.25 0.22-1.45
17 OH Progerstone ng/ml 0.25* 0.08-0.22 3.03* 0.25-2.63
Testosterone ng/dl <15.0 <15.0-24.0 <15.0 <15.0-42.0

Looks like his Androstenedione, Estradiol, and 17 OH Progesterone are high

[labblab]

Well, those results are very interesting, indeed. In contrast to Yukon’s earlier LDDS test, his cortisol level was not elevated above the normal range on this ACTH. So once again, we must wonder whether his elevated LDDS at that time was a reflection of a stressor or illness other than conventional Cushing’s. Looking at this UTenn profile, we see results consistent with that “Atypical Cushing’s” diagnosis that we talked about earlier — normal cortisol but elevations in other adrenal hormones. Based on these results, I don’t think trilostane would be the top treatment recommendation made by the folks at Tennessee. Instead, a combination of melatonin, lignans, and perhaps a low dose of Lysodren would be more likely. Here’s a copy of their general treatment recommendations for you to view yourself.

https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Documents/Treatment%20Considerations.pdf

I’ll be very interested in the internist’s thoughts about this. But do take a look at this treatment recommendation sheet in advance of your discussion with him or your regular vet. As I say, I do think you have some options available other than trilostane.

Marianne

[YukiesMom]

My 13 year old American Eskimo has been diagnosed with Cushing's disease and after going to an Internal Medicine doctor and getting a test done from University of Tennessee it appears that he has elevated Androstenedione, Estradiol and 17 OH Progesterone levels. Cortisone level was within baseline.

We tried him on 10mg of Vetoryl a couple months ago (he weights 32 pounds) and he was very lethargic and in a daze most of the time. We took him off and that is when I brought him for the testing from University of Tennessee.

The Internal Medicine doctor consulted my vet and advise that I needed to start Yukon on 3 mg of Melatonin 1x a day for 7-10 days and then increase to twice a day and add 25mg of Flax Lignans 1x day.

Has anyone done the same thing for their Cushing's dog? Has it helped?

Thank you,

[YukiesMom]

Hi Marianne,

Yes that is what the Internal Medicine doctor me to do - start Yukon on 3mg Melatonin 1x a day and then in 7-10 days increase to 2x day and add flaxseed lignans. Have you seen this really work on Cushing's Dogs? I am really worried. They did not recommend Lysodren because of all the other issues Yukon is having.

[labblab]

Hi again! You’ll see I’ve merged your new thread into your original one, but I’ve changed the overall title to better reflect your current questions. This way, all of Yukie’s info will remain consolidated in one place for us, but hopefully folks will be better aware of the advice you’re seeking right now.

As I wrote above, I was guessing this is the route your internist would go. To reassure you, melatonin and lignans are both generally safe supplements, so I don’t think you’re risking anything by giving this a try. We’ll just have to see whether or not they improve Yukie’s symptoms. Some of our members have seen success; some not as much. It usually does take time, however, for these supplements to produce observable results, so patience can be a great virtue. I’m hoping some of our members who have used these supplements will stop by to talk with you soon.

In the meantime, here’s a Lignans Fact Sheet published by Tennesse that helps guide owners re: obtaining lignans. Your vet may already have shared this with you, but if not, here it is.

https://vetmed.tennessee.edu/vmc/dls/endocrinology/Documents/LIGNANS%20INFORMATION.pdf

Marianne

[Squirt's Mom]

Based on those results Yukon has Atypical Cushing's - meaning the cortisol is normal but 2 or more of the intermediate hormones are elevated. With these results I would not worry about trying Vetoryl (Trilostane) at all and I would put the thought of trying the Lysodren on a back burner. The protocol for Atyipcal is the combination of melatonin and lignans so I am glad they are not prolonging the separation of these two supplements. It typically takes at least 4 months to see any improvements so I am glad they will be combined soon. The melatonin will probably make him a little sleepy at first but he should adjust pretty soon and I would caution you to watch for diarrhea when the lignans are added and if that happens you can lower the dose of lignans and slowly increase. My Squirt started off Atypical and yes, the melatonin and lignans did help her so have hope but also have patience. Just remember it can take several months to see improvements.

[YukiesMom]

You said that Squirt started off Atypical - did he then go into a full Cushing's mode? Do they start out Atypical and then progress? And if so about how long does that take?

[Squirt's Mom]

Yes, my Squirt started out Atypical then her cortisol started to rise and that meant she had true, or conventional, Cushing's with elevated cortisol. In most pups we have seen who have elevated cortisol their intermediate hormones are also elevated - they all seem to go hand in hand very often. Atypical is a controversial form of Cushing's - some vets will simply say there is no such thing, others say it is simply the first stage or a precursor to true Cushing's with elevated cortisol. However, we have had pups who never developed elevated cortisol. It's been a very long time since I've seen one but it has happened.

[YukiesMom]

Well let's hope it happens with Yukon. I am starting the Melatonine tonight. Keep your fingers crossed.

[YukiesMom]

Hi,

It has been a few months since I wrote regarding my 13 year old American Eskimo Yukon and his journey with Cushings that he was diagnosed with in April. Because his Cortisol was not high he could not tolerate the Vetoryl. I did the extensive testing from University of Tennessee and discovered his Androstenedione, Estradiol and 17 OH Progesterone were high so I started giving him Flax Hull Lignans and Melatonin. He has been on it about 5 months and seemed to be doing pretty good. About 5 weeks ago he ingested a fish hook and had to have surgery to have it removed. He then acquired an infection in the incision so he was put on antibiotics for two weeks. Last week we took him in for his laser treatment and the next day he started getting diahrrea and was lethargic and drinking a ton of water and peeing a ton. We took hm to the vet and she said he probably had an upper intestinal inflammation and secondary Pancreatitis as a result of e dehydration and inflammation. We started IV fluids with B12 and Cerenia because he was also eating grass and vomited a couple times. Today we brought him in for his IV and she wanted me to bring his first morning urine. They ran it and his glucose was 1,000mg and they told me he was probably diabetic. They said his fructosamine was normal though. Went to urgent care and they did blood rest it was 486. We have to start insulin injections twice a day. I am so devastated. Is this easy to manage with an already cushings dog?

[labblab]

Welcome back again, although I’m so sorry that Yukon is having even more problems. I’ve merged this newest post into your original thread so we’ll have all his info consolidated in one place. I think the biggest help we can give you right now is to urge you to register on our sister site dedicated to the treatment of canine diabetes. The good folks there are super knowledgeable and will be able to guide you forward with the insulin.

http://www.k9diabetes.com/forum/

In Yukie’s situation, I don’t know that the atypical Cushing’s diagnosis will complicate the diabetes treatment. It’s the combination of high cortisol and elevated glucose levels that can offer challenges. So if Yukon’s cortisol has remained within normal range, that issue wouldn’t be present. Having said that, however, how recently has Yukon’s cortisol been tested? I’m just wondering whether it finally might have started going up, playing some role in the onset of the diabetes. Right at this moment, management of the diabetes definitely takes top priority, though, and cortisol testing might well be inaccurate due to the other current stresses on his system. But retesting of his cortisol might be warranted further down the line. Just a thought to “bookmark.”

So please do head over to the k9diabetes site as well, and I’ll also check in on you there, too.
Marianne

[YukiesMom]

Welcome back again, although I’m so sorry that Yukon is having even more problems. I’ve merged this newest post into your original thread so we’ll have all his info consolidated in one place. I think the biggest help we can give you right now is to urge you to register on our sister site dedicated to the treatment of canine diabetes. The good folks there are super knowledgeable and will be able to guide you forward with the insulin.

http://www.k9diabetes.com/forum/

In Yukie’s situation, I don’t know that the atypical Cushing’s diagnosis will complicate the diabetes treatment. It’s the combination of high cortisol and elevated glucose levels that can offer challenges. So if Yukon’s cortisol has remained within normal range, that issue wouldn’t be present. Having said that, however, how recently has Yukon’s cortisol been tested? I’m just wondering whether it finally might have started going up, playing some role in the onset of the diabetes. Right at this moment, management of the diabetes definitely takes top priority, though, and cortisol testing might well be inaccurate due to the other current stresses on his system. But retesting of his cortisol might be warranted further down the line. Just a thought to “bookmark.”

So please do head over to the k9diabetes site as well, and I’ll also check in on you there, too.
Marianne


Hi Marianne,

Yukon's cortisol has not been tested since May, 2018 when my vet referred me to Blue Pearl to see an internist and he submitted the test to the University of Tennessee. He has been doing very well on the flax hull lignans and melatonin, but you are right maybe his cortisol has now began to rise. Thanks for referring me to the diabetes support group. I will be writing and joining today. This just breaks my heart he was doing so good and all of a sudden this fish hook incident and surgery made us go way backwards.

[labblab]

I’m so happy to see that you’ve posted over on k9diabetes! For the benefit of our members here, this is a link to your K9D thread so that we can all keep tabs on you over there, as well ;-)

http://www.k9diabetes.com/forum/showthread.php?t=7763

Marianne

[YukiesMom]

I’m so happy to see that you’ve posted over on k9diabetes! For the benefit of our members here, this is a link to your K9D thread so that we can all keep tabs on you over there, as well ;-)

http://www.k9diabetes.com/forum/showthread.php?t=7763

Marianne

Hi Marianne,

The last 10 days havebeen quite a challenge for me since Yukon was diagnosed with type 1 diabetes. We have been doing the insulin injections and checking his blood levels various times of the day. His blood glucose has not dropped under 500 in the last 10 days and were doing everything right I think.

I started googling all of his medications he's on to see if they interact with insulin. I found some very interesting articles on melatonin and insulin resistance. One of the Google searches said that melatonin binds to receptors on pancreatic cells to suppress insulin secretion. This causes them to be more sensitive to the effects of melatonin, which results in an exaggerated inhibition of insulin secretion. That makes their bodies less effective at regulating blood sugar.

My question to my K9 Cushing's Friends is if I take him off the melatonin is that OK? He will still be on the flax hull lignans. When I did the test at the University of Tennessee in May 2018 his cortisol was within normal levels it was three other hormones that we're off.

I did call the University of Tennessee today and asked about the melatonin and someone there said there was no clinical Proof that melatonin throws off insulin, but they have seen many cases of this happening. He told me to give it at least a month to maybe see results.

Has anyone had experience with us? I am also on the diabetes forum and they told me to reach out to my Cushing's friends to see if anybody else had this situation. Thank you in advance

[labblab]

Hi again! I’ve just been over to your K9D thread, and added this reply. If other folks here have additional thoughts, I’m surely hoping they’ll chime in, as well ;-).


I’m really glad you’ve made the appointment with the internist. Yukie’s situation is complicated enough that guidance from a specialist should be very helpful!

In all my years on K9C, I don’t know that we have ever discussed the impact of melatonin on diabetic management. In honesty, I can probably count on one hand the number of dogs on our forum who have presented with the dual diagnosis of “Atypical” Cushing’s as well as diabetes. As I’ve talked about before, it’s the combo of the elevated cortisol of traditional Cushing’s and elevated glucose levels that we commonly encounter. So Yukie’s situation is a bit of a new frontier for us all.

Given Tennessee’s anecdotal report of melatonin complicating diabetic management, I believe I’d stop it, too. Partly because its efficacy in resolving Cushing’s-like symptoms is hit-and-miss even when diabetes is not involved, and partly because I don’t think it helps with lowering progesterone/17-hydroxyprogesterone levels (which sound to me to be the most worrisome elevations in Yukie’s profile in terms of insulin resistance).

Please bear in mind that all of this is largely supposition on my part. I’ll feel a whole lot more comfortable when you can get some professional feedback from a specialist. In general, there remains a lot of controversy about the significance/impact of elevated adrenal hormones other than cortisol, and the “Atypical” diagnosis is not one that is even universally recognized among endocrinologists. So this is a long-winded way of saying that I’d probably ditch the melatonin right now, too, if there’s any chance that it’s interfering with the insulin.

Looking ahead, if elevated adrenal hormones — including cortisol — do seem to be complicating things for Yukie, there is a medication alternative to Vetoryl named Lysodren. It’s an older medication and is no longer used as frequently as Vetoryl to treat traditional Cushing’s. But unlike Vetoryl, it has the ability to lower several of the other adrenal hormones, including progesterone, as well as cortisol. So it is much more powerful than melatonin, and might be considered down the road.

By the way, good job for researching the possible link between melatonin and insulin resistance! This may be very helpful information for all of us on K9C.

Marianne

[YukiesMom]

Hi Everyone,

I have been giving my dog Yukon Flax Hull Lignans and Melatonin for his Atypical Cushing's since May, 2018. He was recently diagnosed with Diabetes as well and we are having a hard time regulating his Blood Sugar.

I have a question for anyone who has their dogs on this holistic approach - should I be giving him his Lignans and Melatonin at the same time in the morning? I usually give him his Lignans at around 6:30 a.m. and Melatonin at 8:00 a.m., but I am starting to question whether they should be given together at the same time.

I have been online and can pull no articles that tell me when to administer.

Thank you,

[labblab]

Welcome back to you and Yukie. You know, that’s an interesting question, and not one that I’ve seen discussed here. My best advice would be to contact the folks in the Endocrinology Department at the Univ. of Tennessee/Knoxville in order to find out their thoughts. Since it is their research that has prompted treatment using the combination of melatonin and lignans, I think they’d be your best source for accurate information in that regard. Here’s a link to their contact page. I don’t know how much detail they will go into with pet owners, but it ought to be worth giving a shot. And for sure, I’m certain they’d be happy to talk with your vet.

https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Pages/default.aspx

Marianne

[YukiesMom]

Welcome back to you and Yukie. You know, that’s an interesting question, and not one that I’ve seen discussed here. My best advice would be to contact the folks in the Endocrinology Department at the Univ. of Tennessee/Knoxville in order to find out their thoughts. Since it is their research that has prompted treatment using the combination of melatonin and lignans, I think they’d be your best source for accurate information in that regard. Here’s a link to their contact page. I don’t know how much detail they will go into with pet owners, but it ought to be worth giving a shot. And for sure, I’m certain they’d be happy to talk with your vet.

https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Pages/default.aspx

Marianne

Thank you Marianne I called them today and left a message for an internal medicine doctor to call me back. Actually because of Yukons diabetes the doctor took him off the melatonin again and upped his insulin so I guess I don't have to worry about it for now. This is very frustrating. My poor Yukon is going through so much and I can't seem to find someone to help us out

[YukiesMom]

Welcome back to you and Yukie. You know, that’s an interesting question, and not one that I’ve seen discussed here. My best advice would be to contact the folks in the Endocrinology Department at the Univ. of Tennessee/Knoxville in order to find out their thoughts. Since it is their research that has prompted treatment using the combination of melatonin and lignans, I think they’d be your best source for accurate information in that regard. Here’s a link to their contact page. I don’t know how much detail they will go into with pet owners, but it ought to be worth giving a shot. And for sure, I’m certain they’d be happy to talk with your vet.

https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Pages/default.aspx

Marianne

Thanks Marianne,

I am really not having much success at all treating all his conditions.

He was originally diagnosed May, 2018 with “Atypical" Cushings Disease after doing testing from the University of Tennessee. It was determined through testing that his Cortisol levels are normal, but his Androstenedione ng/ml, Estradiol pg/ml and 17 OH Progesterone ng/ml levels are high.

Before this testing occurred we did the LDDS test at our local vet and he was put on 10mg Vetoryl, but after about 6 days on Vetoryl he could not handle it (lethargic, personality change). Our vet called the manufacturer and they advised to take him off the Vetoryl so I did. That is when we decided to do further testing with University of Tennessee.
The reason the Vetoryl was not successful is because it lowers the Cortisol, and his was normal. Vetoryl also increases the other hormones, which Yukon’s were already severely high. Because of these findings I decided to do a more holistic approach as recommended by the University of Tennessee and I started him on Flax Hull Lignans and Melatonin. It seemed to be helping with the panting, excessive drinking and hunger.

October, 2018 he was diagnosed with Diabetes. We started him on 4 units of Vetsulin (30 pounds) and he is now up to 11 units and we still cannot control his Blood Glucose - Fructosamine test was done a couple weeks ago and it was 413. I am now consulting with an Internal Medicine doctor and I made her aware of an article I read about Melatonin possibly interfering with regulation of insulin. She advised me to take him off the Melatonin. Since then his levels have been getting higher, especially at night.

I contacted my regular vet and asked if we should do the Stim Test again and send to the University of Tennessee and she said probably. Does anyone know of an experienced vet in the Detroit Michigan area that has an expertise is both Cushings and Diabetes?

[labblab]

I’m so sorry you guys are still having such a tough time! I’ve been following your thread over on K9D, and it sounds as though the folks over there still aren’t considering the 11 units of insulin to be a very high dose. If that’s true, I’m not sure why your current vets are being so hesitant to “up” the insulin if Yukie remains uncontrolled. It has to feel so exhausting and frustrating to see such little progress being made over these past weeks.

I’m afraid I don’t know any specific vets in the Detroit area. There has to be somebody competent, but I don’t have a recommendation to make. You could take a look at this IMS database to see who else comes up, since you’re not entirely comfortable with the IMS you’re seeing now.

http://find.vetspecialists.com/

My other thought might be to bite the bullet and make the drive to the outpatient clinic at Michigan State’s vet school at E. Lansing. I just checked, and it looks like a 90-minute drive from Detroit. But the MSU vet school is very highly regarded nationally, and especially for endocrinological services. For instance, their lab offers the premiere university-based thyroid analysis in the country. At MSU, you’d have the benefit of collaborative consultation with a full team of specialists. They would definitely have extensive experience with both diabetes and Cushing’s. And according to their website, they accept new patients either through vet referral or direct contact from owners.

https://cvm.msu.edu/hospital/about

Given all the frustration you’ve been through thus far, it might really be worth a consultation. Subsequently, it might turn out that they could offer guidance to your local vet in order to avoid the need to return to MSU itself very frequently. Anyway, just a thought to consider.

Marianne

[YukiesMom]

I’m so sorry you guys are still having such a tough time! I’ve been following your thread over on K9D, and it sounds as though the folks over there still aren’t considering the 11 units of insulin to be a very high dose. If that’s true, I’m not sure why your current vets are being so hesitant to “up” the insulin if Yukie remains uncontrolled. It has to feel so exhausting and frustrating to see such little progress being made over these past weeks.

I’m afraid I don’t know any specific vets in the Detroit area. There has to be somebody competent, but I don’t have a recommendation to make. You could take a look at this IMS database to see who else comes up, since you’re not entirely comfortable with the IMS you’re seeing now.

http://find.vetspecialists.com/

My other thought might be to bite the bullet and make the drive to the outpatient clinic at Michigan State’s vet school at E. Lansing. I just checked, and it looks like a 90-minute drive from Detroit. But the MSU vet school is very highly regarded nationally, and especially for endocrinological services. For instance, their lab offers the premiere university-based thyroid analysis in the country. At MSU, you’d have the benefit of collaborative consultation with a full team of specialists. They would definitely have extensive experience with both diabetes and Cushing’s. And according to their website, they accept new patients either through vet referral or direct contact from owners.

https://cvm.msu.edu/hospital/about

Given all the frustration you’ve been through thus far, it might really be worth a consultation. Subsequently, it might turn out that they could offer guidance to your local vet in order to avoid the need to return to MSU itself very frequently. Anyway, just a thought to consider.

Marianne

Thanks Marianne,

I actually spoke with someone at the University of Tennessee who is working with my regular vet now to hopefully figure out how to treat Yukon. We had another ACTH Stim done yesterday and its is being overnighted to UofT for analysis of all the hormones.

Lysodren was mentioned as possibly being used - most likely the maintenance dose which would be 125mg 3x a week.

I am really scared of that drug because I have read such bad things about it. On the other hand it appears to be one of the only drugs available that lowers the other sex hormones.

Can anyone add insight on their experience with Lysodren?

[labblab]

Through the years, we’ve had lots of members who’ve done very well on Lysodren. Especially if you are dosing at the lower maintenance level, the risks of unwanted side effects should be minimized. Please do let us know how you guys end up proceeding.

Marianne

[Squirt's Mom]

My Squirt started out Atypical and when her cortisol started to rise we used Lysodren. When Trilostane (Vetoryl) first came out that is the drug I wanted to use if needed but as more and more dogs started taking it and getting very sick because the starting dose at that time was much too high I quickly changed my mind. Over the years I have come to prefer Lysodren and that will always be my first drug of choice with which to treat a cush pup. When my another dog was diagnosed with Cushing's (incorrectly it turned out but that is another story) her vet wanted her on Vetoryl but I insisted on Lyso. I am MUCH more comfortable with Lyso than Vetoryl. For one thing we know exactly what Lysodren is doing and where - it works ONLY on the adrenal glands while Vetoryl works on the axis, or loop, between the pituitary, hypothalamus, and adrenal glands. Many thing happen along that loop other than cortisol messaging (info to produce and release cortisol). Since you will be going straight to maintenance, like we did with Squirt, you don't have to worry about the "scary" part - the load, or induction. Start with the lowest dose and most widely space schedule and that will make you more comfortable as well. ie give her the lowest starting dose (25mg/kg/day) 2 days a week. Then you can increase the days, say 3 days a week, if that is not enough and you have plenty of room to increase the dose if needed to 50mg/kg/day. I chose to start with the highest dose I think it was 3 days a week with Squirt and eventually went to every 3rd day. We never had any problems at all, not with Squirt nor with the one that was misdiagnosed. So take a deep breath and know you are in good hands here. We will help you any way we can. You can also know that at least one person will always prefer Lysodren. ;)

Hugs,
Leslie

[YukiesMom]

My Squirt started out Atypical and when her cortisol started to rise we used Lysodren. When Trilostane (Vetoryl) first came out that is the drug I wanted to use if needed but as more and more dogs started taking it and getting very sick because the starting dose at that time was much too high I quickly changed my mind. Over the years I have come to prefer Lysodren and that will always be my first drug of choice with which to treat a cush pup. When my another dog was diagnosed with Cushing's (incorrectly it turned out but that is another story) her vet wanted her on Vetoryl but I insisted on Lyso. I am MUCH more comfortable with Lyso than Vetoryl. For one thing we know exactly what Lysodren is doing and where - it works ONLY on the adrenal glands while Vetoryl works on the axis, or loop, between the pituitary, hypothalamus, and adrenal glands. Many thing happen along that loop other than cortisol messaging (info to produce and release cortisol). Since you will be going straight to maintenance, like we did with Squirt, you don't have to worry about the "scary" part - the load, or induction. Start with the lowest dose and most widely space schedule and that will make you more comfortable as well. ie give her the lowest starting dose (25mg/kg/day) 2 days a week. Then you can increase the days, say 3 days a week, if that is not enough and you have plenty of room to increase the dose if needed to 50mg/kg/day. I chose to start with the highest dose I think it was 3 days a week with Squirt and eventually went to every 3rd day. We never had any problems at all, not with Squirt nor with the one that was misdiagnosed. So take a deep breath and know you are in good hands here. We will help you any way we can. You can also know that at least one person will always prefer Lysodren. ;)

Hugs,
Leslie

Thank you Marianne and Leslie - that makes me feel better. Yukon has not been acting right since the ACTH Stim yesterday - very lethargic just laying around. He ate really good and went for a walk, but seems to be under the weather. I wonder if this is just a side effect of the injection.

[Squirt's Mom]

Not at all uncommon for them to feel a bit off the beam after the ACTH. It is a stimulation test that causes the release of cortisol. He should be better soon.

[YukiesMom]

Not at all uncommon for them to feel a bit off the beam after the ACTH. It is a stimulation test that causes the release of cortisol. He should be better soon.

Hi Everyone,

Just wanted to update you on Yukon's situation. I did a second STIM test with my regular vet (University of Tennessee adrenal panel) to recheck all Yukon's Hormone levels and he still does not have elevated cortisol, and his other hormones got a little better.

He does not have high estradiol anymore, only Androstenedione and 17OH Progesterone. I am hoping that is because I was treating with the flax hull lignans and melatonin. We are off the Melatonin now because it could create insulin resistance, so I have put him on the Lignans twice a day an hour after his insulin injection.

I am not sure if I should try to treat him with Lysodren and he obviously cannot take Vetoryl because that increases the two hormone levels that are already high. Is there anything else that anyone knows of that can reduce the two hormones that Yukon is showing as high?

Thanks,

[Squirt's Mom]

it is the combination lignans and melatonin that help control the intermediate hormones. One without the other will not do the trick and you will probably find the ones that have lowered rising again. Lysodren can control all those intermediates with the possible exception of estradiol. Lyso works ONLY on the adrenal glands and estradiol can be produced outside the adrenals in some rather odd places like hair follicles to name one. So as long as the estradiol is produced by the adrenals the Lyso will help with it as well but any of that hormone produced elsewhere the drug can't reach.

[Harley PoMMom]

That's awesome that those hormones have come down, especially the estradiol as it can be difficult to get normalized. How are Yukon's symptoms? And is his BG controlled?

You're doing a great job!

Lori

[YukiesMom]

That's awesome that those hormones have come down, especially the estradiol as it can be difficult to get normalized. How are Yukon's symptoms? And is his BG controlled?

You're doing a great job!

Lori

Hi Lori,

Thanks I am really trying. Yukon is going pretty good, he does not have a pot belly anymore, but I do notice his hair shedding a little more since I discontinued the melatonin. His BG is getting lower - it stays around 300 with drops down to the 200's.

As long as he is acting good I am OK with it - he turned 14 on January 9, 2019.

[Harley PoMMom]

As long as he is acting good I am OK with it - he turned 14 on January 9, 2019.


Happy belated Birthday, Yukon!!!

[Squirt's Mom]

Happy belated 14th Birthday, Yukon!


and many more!!

[YukiesMom]

Yukon has had Atypical Cushings for a couple years and was diagnosed one year ago with diabetes as well. We finally got his diabetes regulated the last month or so and he is pretty much gone blind but he's doing pretty good considering the circumstances.

I just had his 6 month blood work done and his BUN and Creatinine are elevated. My vet thinks he has a G.I. bleed from the Cushing's and that's what's causing the numbers to be elevated.

She said red and white blood cells and heart are fine. Has anyone heard of this with Cushing's? I just thought when those two things were elevated it was a sign of kidney problems. His urine in the morning is very concentrated which is good.

[Squirt's Mom]

First, I have merged your latest post into Yukon's original thread. We like to keep all posts about each pup in ONE place. That way it is easier to keep up with the history. You may want to bookmark this thread so you can find it in the future. ;)

I am a bit confused....has Yukon definitely been diagnosed with Cushing's? In Jan of this year the UTK test still does not support a diagnosis of Cushing's because the cortisol was still normal. Has there been more testing since? Concentrated urine does not typically happen with a cush pup; their urine is usually quite dilute.

As for a GI bleed caused by Cushing's - personally I don't remember that happening in any pups here but it is a possibility. HOWEVER the dog needs to have Cushing's before it can cause anything and that has not been clarified so far. :) Was any vomiting involved?

Elevated BUN and Creatinine used to be the only guidelines we had for kidney disease in dogs. These values did not let us know there was a problem until something like 75% of kidney function was lost. Now there is a new test called the SDMA that catches kidney disease MUCH earlier. If this condition is a consideration I would demand the SDMA asap.

[YukiesMom]

The last test we had done his cortisol was still within range but all the other sex hormones were elevated. Since he was diagnosed with diabetes we have been trying to regulate that. I finally got that somewhat regulated and it seems like he's back to all the cushings symptoms. Heavy panting, heavy shedding, drinking tons of water and increased appetite. I am wondering if maybe the cortisol is now going up and he's in full blown Cushing's and that's why all the readings came out high.

Maybe I should have another ACTH test done. But I will suggest that other test SDMA to my vet. I have noticed the last month his back legs are really getting weak and they seem to be falling down and he has no control of them sometimes he just slips down.

[YukiesMom]

Hi Everyone,

So Yukon has been sneezing constantly the last couple weeks so I took him to the Vet and she checked him out and said that he might just have a virus. A couple days later I started seeing yellow/green mucous coming out of one nostril so she put him on azythromycin and it started to make him a little sick. I took him off the antibiotic after 5 days because of this. He normally has a great appetite because of the Cushings, bu the last 3-4 days he picks at his food and at least once a day doesn't eat it all. It makes it hard because he has diabetes too.

I also noticed the last week or so he is really having weakness in his hind legs. He stands with his legs almost going down to the ground, but he walks fine. He has a hard time now getting up one set of stairs suddenly. We are afraid he is going to fall down them so we pick him up.

I am going to go to the vet this week and get some blood work done, but has anyone had these issues with sneezing, lethargy and decreased appetite? I am really getting worried.

[labblab]

The last test we had done his cortisol was still within range but all the other sex hormones were elevated. Since he was diagnosed with diabetes we have been trying to regulate that. I finally got that somewhat regulated and it seems like he's back to all the cushings symptoms. Heavy panting, heavy shedding, drinking tons of water and increased appetite. I am wondering if maybe the cortisol is now going up and he's in full blown Cushing's and that's why all the readings came out high.

Maybe I should have another ACTH test done. But I will suggest that other test SDMA to my vet. I have noticed the last month his back legs are really getting weak and they seem to be falling down and he has no control of them sometimes he just slips down.
Hello again. You’ll see that I’ve merged your post into your original thread about Yukie. Also, I’m quoting above the reply you posted back in September in order to give us a little summary as to where things stood then. I see that as far back as last fall you were seeing increasing weakness in his rear legs. Did that end up stabilizing again for a while and is now worsening again, or has it remained pretty consistent as a problem during these past few months? Did you end up having any blood work done back then?

As far as the sneezing and nasal discharge, my best guess would also be some sort of infection. It’s indeed frustrating that antibiotics can often cause GI upsets, and I sure do understand why that’s especially a problem for a diabetic. However, if you stopped the course of antibiotics before it was finished, the infection may still be active. If Yukie is still sneezing and not feeling perky, that seems likely to me. As far as the continuing lack of appetite, I really don’t know aside from the possibility that he’s just generally feeling unwell from the infection.

I definitely think it’s a good idea to have him checked out again by the vet this week, and some bloodwork run. And if needed, perhaps he could be given a different antibiotic this time around — one that won’t upset his stomach as much. Please let us know what you find out, OK?

Marianne

[YukiesMom]

Hello again. You’ll see that I’ve merged your post into your original thread about Yukie. Also, I’m quoting above the reply you posted back in September in order to give us a little summary as to where things stood then. I see that as far back as last fall you were seeing increasing weakness in his rear legs. Did that end up stabilizing again for a while and is now worsening again, or has it remained pretty consistent as a problem during these past few months? Did you end up having any blood work done back then?

As far as the sneezing and nasal discharge, my best guess would also be some sort of infection. It’s indeed frustrating that antibiotics can often cause GI upsets, and I sure do understand why that’s especially a problem for a diabetic. However, if you stopped the course of antibiotics before it was finished, the infection may still be active. If Yukie is still sneezing and not feeling perky, that seems likely to me. As far as the continuing lack of appetite, I really don’t know aside from the possibility that he’s just generally feeling unwell from the infection.

I definitely think it’s a good idea to have him checked out again by the vet this week, and some bloodwork run. And if needed, perhaps he could be given a different antibiotic this time around — one that won’t upset his stomach as much. Please let us know what you find out, OK?

Marianne

Thanks Marianne - his back legs started doing a little better and then the last couple months I have noticed he seems to be dropping down in the rear end when he stands for a long time and then has to sit down eventually. I am actually going to order one of those Assisi Loops to see if that helps.

I will definitely keep you posted. Of course, I always think the worst case scenario and what keeps running through my mind is that possibly the pituitary gland tumor is getting larger and obstructing his sinuses. My vet of course wants me to go to an emergency clinic and get a rhinoscopy, but I just can't justify spending the money as of now.

[YukiesMom]

So now I did Yukons blood work he has pancreatitis but the thing that throws me off more than anything is that the doctor said now his Cushing's might be causing a low cortisol that would be Addison's disease. He has diabetes as well and I only have him on the Flaxhull Lignans.

How can a dog go from Cushing's to Addison's?

[Squirt's Mom]

Good to hear from you again but sorry to hear Yukon has pancreatitis. I hope he is soon well and back on his feet. As for Cushing's causing Addison's, I've never heard nor read of any such thing...but I could be wrong; I don't claim to be an expert. ;) If the dog were on treatment then an overdose of the med, Vetoryl/Trilostane or Lysodren/Mitotane, could cause an Addison's crisis (not permanent) or true Addison's (permanent) by driving the cortisol too low and damaging the adrenal glands. Lignans doesn't have that ability at all to my knowledge. There is always the possibility that the Cushing's was a misdiagnosis in the first place but I think you would have seen signs of low cortisol long before now if that were the case with Yukon.

What caused the vet to say such a thing? Did they do an ACTH or are you seeing signs of Addison's? Signs may include weakness, depression, lack of appetite, vomiting, diarrhea, and occasionally increased thirst (polydipsia) and increased urine production (polyuria). Clinical exams may find dehydration, weak pulses and sometimes a slow, irregular heart rate. Lab work might show an increase in CREA and BUN, low GLUC, changes in WBC, increased potassium, decreased aldosterone, and dilute urine. BUT pancreastitis can throw a great many lab results out of whack so with this condition in play I wouldn't trust any diagnostics tests for either Cushing's or Addison's right now. Once Yukon is over the pancreatitis then you can take a look if needed.

Please let us know how he is doing!
Hugs,
Leslie