Switching from Vetoryl to Lysodren

[MJ McClain]

Hi, I am new to these boards and would appreciate any advice to help my dog. Bella is 10 year old labradoodle, 70 pounds, diagnosed with Cushings in July of 2013, via ACT Stim test. The vet put Bella on 60 mg of Vetoryl. Within a few days Bella's excessive drinking and panting ceased and she returned to being more comfortable. With the exception of recurring bladder infections bella was fine until the middle of September. The vet believes (no confirmation despite seeing several different vets) that Bella went into an Addisonian Crisis. Bella stopped taking the Vetoryl for a week and vastly improved although the symptoms of Cushings came back, excessive drinking, excessive urination, panting and generally uncomfortable. A week later Bella was put back on Vetoryl but at a much lower dose 30 mg. Bella's blood was drawn and ACTH test done again and sent to University of Tennessee. She has had two tests done a month apart at the University of Tennessee. The university has recommended taking Bella off the Vetoryl and switching to Lysodren. The recommendation is Bella to be off of the Vetoryl for 30 days before starting the Lysodren. I am worried about managing symptoms for 30 days - excessive drinking/urination being the symptom so hard to manage in a large dog. Bella also takes soloxine (thyroid/hormone medication, once a day) Amlodopine (blood pressure medication, once a day) and 6 mg melatonin twice a day. Sorry I don't have the exact results of all of Bella's tests they are at my vets office. She has had several ACTH Stim tests and two separate blood tests have been sent to the University of Tennessee. Results of those tests have shown Bella has Atypical Cushings with sex hormone irregularities.

Did anyone else in the group have to switch their dog from vetoryl to lysodren?

[addy]

Hi and Welcome,

We have had dogs make the switch but I think we need to back up a bit. We need more information if possible.

An Addison's crisis is confirmed with testing of cortisol and electrolytes. Your vet should "know" not believe your pup had one.

I think we need more information. Could you tell us what lead to looking to see if your pup had Cushings? How was your dog diagnosed? What were the results of the test? Could you list the ACTH tests here your pup has had so far? Could you list the results of the UTK adrenal panel?

I am so glad you found us. We just need more information.

[Squirt's Mom]

Hi and welcome to you and Bella! :)

If you would, please get copies of all the tests done to diagnose the Cushing's and those that have been done since treatment started. That will help us help Bella a great deal! ;)

If Bella is truly Atypical, that means her cortisol is normal but one or more of her intermediate hormones is elevated. UTK does not recommend Vetoryl for Atypical pups tho some vets use it any way and the pups do ok. The reasoning behind this is that studies have shown that Vetoryl causes elevations in some of the intermediates. You will find that not everyone agrees on Atypical nor the treatments for it.

What is recommended is a COMBINATION of melatonin and lignans from either flax or spruce as the initial treatment. If after 4 months signs are not improved and the hormones are not low enough, then a maintenance dose of Lysodren is added - NO loading with Atypical pups. So the first step is to add the lignans to her regime...after stopping the Vetoryl that is. Give that time to work, then if needed add the Lysodren which will be given 2-4 times a week along with the melatonin and lignans.

How recently has her thyroid function been checked? If it has been a while, I would also have that done asap and I would ask for a full thyroid panel.

How is her appetite?

How much does she weigh?

What did Bella act like when the vet thinks she had an Addisonian crisis? Was she given an ACTH at that time? Was she put on prednisone?

I'm glad you found us and look forward to seeing those test results as well as learning more about the both of you!
Hugs,
Leslie and the gang

[MJ McClain]

It has been awhile since Bella had her thyroid checked, the last check was about 5 months ago. Bella's appetite is voracious - she seems to be always hungry and salivates excessively when she is about to eat. She never salivated before diagnosis of Cushings. Bella weighs 70 pounds. She was given an ACTH test when the addisonian crisis happened but the results were not typical of an addisonian crisis. - Bella was extremely weak in her back end and had trouble standing, and was lethargic. The vet thought it was an addisonian reaction to the vetoryl or possibly just a reaction to the dosage of vetoryl. After Bella was off the vetoryl for a week she improved greatly. But the symptoms of cushings came back, drinking, urination, and panting. The vet put Bella back on the vetoryl but at 30 mg instead of 60 mg. She has been doing okay on that dose. But the latest results from her University of Tennessee test show that her sex hormone values have changed. After her first test by the University of Tennessee 3 sex hormone values were not normal. After her second test at University of Tennessee (60 days between tests) 6 sex hormone values were not normal. Where do I get the lignans? - my vet mentioned putting Bella on Lignans but said that he did not feel there was strong evidence that Lignans would help.

[Squirt's Mom]

I think the proof is in the pudding, as they say, if her sex hormones (Intermediate hormones) have increased instead of decreasing with the Vetoryl (Trilostane) on board. This is what studies have shown - this drug increases the intermediate (sex) hormones. ;) If Bella's cortisol is normal, which it should be with an Atypical pup, then I'm not real sure why the Trilo (Vetoryl) was given in the first place. :confused: Seeing those test results will sure help! :)

My Squirt was Atypical and the lignans and melatonin lowered all her intermediates and kept them under control for several years before her cortisol began to rise, requiring Lysodren. The lignans can be purchased at several places online. I'll give you a link or two. We can also help with the dose she will need. Is Bella taking the melatonin twice a day? How much is she taking? We can help with the dosing for that as well.

The first thing I would do is get the thyroid checked and do the full panel just to be sure. Hypothyroidism is one of several conditions that share many of the same signs as Cushing's - including excess drinking, peeing, and increased appetite. ;)

I just realized you and Bella are on the FB group, too! Hi! I'm the Leslie from there. Glad to have you join us here! :cool::):cool:
Hugs,
Leslie and the gang

[MJ McClain]

Bella has been diagnosed as having a thyroid disorder, in my first post, I list her medications. She takes soloxine for her thyroid. My vet has been monitoring her thyroid condition for over two years and feels it is under control with her current dose of soloxine. I will be asking for a retest though since it has been 5 months since her last thyroid test.

Bella's symptoms began about year ago, they were potbellied appearance, hair loss, panting, excessive drinking/urination, recurring bladder infections, recurring skin infections, and increased appetite. Bella had the ACTH test and was diagnosed as cushings. We also had an ultrasound done at the time to check to see if there were any visible tumors on the adrenal glands. There were no visible tumors on the adrenals.

I have some of Bella's records from early in diagnosis (6/17/13). Her dex suppression results (vet records are difficult to read/follow):
Pre-dex = 6.7,
post 4 hr dex = 4.1
post 8 hr dex = 1.6

What is FB? Is that Facebook, if so, you might have me confused with someone else, I'm not on Facebook.

If you could post the links to the lignans that would be wonderful as I would like to find a reliable source for them.

Thanks so much - Mary Jo

[labblab]

Hello and welcome from me, too. From what you have written above, it looks as though Bella's original diagnosis was based on elevated cortisol rather than just upon elevated intermediates alone. Either way, I think the most important question right now is whether or not her symptoms are being controlled on the current dose of Vetoryl. You have told us she is doing good on the 30 mg. dose. If so, I don't understand why you would want or need to be making any medication change. It is true that trilostane is known to elevate certain adrenal hormones, but this is true for every dog who takes the drug and does not necessarily create any new problems. So unless you are having trouble controlling Bella's Cushing's symptoms with the Vetoryl, I do not see why a medication shift/addition is being recommended if it is solely on the basis of intermediate hormone elevations that appear on her labwork.

Marianne

[Squirt's Mom]

WOW! There is a member on the Canine Cushing's Awareness group on Facebook with the exact same user name and a dog with the exact same name, and your first post is identical to a post on that Facebook group! WEIRD!

https://www.facebook.com/groups/89435412886/

AND now this is really weird - I have been talking to that MJ McClain about their Bella this morning but they are no longer showing up on the group. :confused::confused::confused:

hummmmm...anyway I will give you the same links I gave that MJ McClain on the lignans. They had used the HRM but stopped and are using only melatonin now.

The first is the HMR lignans from Spruce. We lost control of Squirt's intermediates (sex hormones) when I switched from the SDG to the HMR but others have had success with it -

Swanson –
http://www.swansonvitamins.com/SWU207/ItemDetail?n=0

This is the brand of SDG lignans from flax that I used. You can use any brand but look for the words LinumLife® in the ingredients -

VitaCost brand -
http://www.vitacost.com/Vitacost-Flax-Seed-Lignan-Extract/?ntt=nsi%203002498

Hugs,
Leslie and the gang

[addy]

The vet put Bella back on the vetoryl but at 30 mg instead of 60 mg. She has been doing okay on that dose. But the latest results from her University of Tennessee test show that her sex hormone values

If Bella was doing ok on the new 30 mg Vetoryl dose, what prompted your vet to do a UTK panel rather than a standard ACTH test to check her cortisol levels? Sometimes when we lower our dog's cortsiol we unmask other problems. It is also possible for them to have a side effect from Vetoryl as well.


I am sorry for all the questions, we are just trying to sort out what has been going on with Bella and sometimes that is hard when we are all writing back and forth.:):)

Your dog originally was tested and showed elevated cortisol, so Bella is not "atypical" she has Cushings. Most dogs will have some elevations in some of their intermediate hormones and what that means for the dog just depends on the individual dog. Some vets get confused about the UTK adrenal panel. I know mine did.

We have had some dogs do a thirty day wash out, some do 2 weeks. Dechra ( Vetoryl manufacturer) told our IMS that the only time she needs to do a wash out is when switching from Lysodren to Vetoryl. Yet most endocrinologists do suggest a wash out.

[MJ McClain]

Hi Addy,

In September when Bella had her suspected Addisonian crisis or reaction to Vetoryl (no vet is quite sure what happened) Bella did have a very low dose of prednisone injected and that helped her recover. That is when I delved more in research of cushings and found out about the University of Tennessee and their research of k9 cushings. I asked my vet to send Bella's blood to them for further testing.

After the two tests sent to Tennessee 60 days apart showed further involvement of Bella's sex hormones - the recommendation was to switch Bella from vetoryl to lysodren. Bella has been doing fine on the lower dose of vetoryl 30 mg (the crisis happened when Bella was on the higher dose 60 mg).

Do you think removing Bella from vetoryl (since it is suppressing her cushings symptoms) might be unnecessary? What about the changes in her sex hormones? I will say when we added the melatonin to Bella's drug regimen - it seemed to really help with the panting and ability to sleep and stay comfortable (less pacing).

The reason for the confusion on the addisonian crisis is all of Bella's physical symptoms pointed to addisonian crisis but Bella's tests came back borderline addisonian - Bella was in a very bad way - not eating, could not stand at one point (for about 8 hours). The doc was confused because Bella's symptoms were very bad but her bloodwork was not correlated to her symptoms.

Also, I mentioned in an earlier post that Bella also has high blood pressure which was attributed to the cushings. She takes amlodipine for her high blood pressure.

I really appreciate the help and recommendations from everyone, I am so glad I found this group.

[labblab]

If the Vetoryl is adequately controlling Bella's Cushing's symptoms, then I would not be switching her medication if she were my own dog. There really just doesn't seem to be any reason to do so. Later today I will try to add a link that discusses trilostane's known effect re: elevating some of the other adrenal hormones. But as noted above, this is to be expected and doesn't seem to be a contraindication to the use of the drug if it is not associated with new or rebounding symptoms.

Could you possibly obtain and post the actual numerical test results when Bella suffered her Addisonian issues? Did the blood testing involve both an ACTH and also basic blood chemistries (most importantly, levels of potassium and sodium)? I am just curious as to what your vet is labelling as borderline. Also, it is possible for electrolyte imbalances (potassium and sodium levels) to cause problems even when cortisol does not dip too low.

But for me, the bottom line would be how she is responding to this lower Vetoryl dose. "If it ain't broke," I wouldn't be messing with trying to fix it! ;)

Marianne

[MJ McClain]

Hi Marianne,

I agree with you - I would like to keep Bella on the vetoryl. My vet seemed very concerned about the changes in the sex hormones. He did say that the vetoryl was the cause of the changes so he thought it would be good to switch to the lysodren. I think my vet's other concern (and mine too) was the crisis in September - that probably was caused by dosing too high (60 mg) on the vetoryl. Bella started the vetoryl in July and was fine until mid September. She has been on the lower dose of Vetoryl (30 mg) since early October. Bella also developed high blood pressure, in October. So I think the question is what problems are attributed to cushings and what problems might be attributed to the vetoryl.

[labblab]

OK, here is a paragraph written by UTK's researcher, Dr. Jack Oliver, that summarizes trilostane's potential effect on adrenal hormones other than cortisol:


​Enzyme inhibition by trilostane occurs for 3-beta hydroxysteroid dehydrogenase, but also for 11-beta hydroxylase. Thus, 11-deoxycortisol levels build-up in dogs treated with trilostane. It is also apparent that other intermediate steroid levels increase (androstenedione, 17-hydroxyprogesterone, estradiol and progesterone) in dogs treated with trilostane, which could be due to the 11-beta hydroxylase inhibition, and possibly 21-hydroxylase enzyme inhibition.

However, the jury remains "out" as to whether these elevations are ever directly problematic for the majority of dogs who are treated with trilostane. Here is the summary of a very interesting paper found by one of our other staffers, Glynda.


Occult HAC [Atypical Cushing's] due to adrenal secretion of sex hormones has never been proven. In the literature, both human and veterinary, evidence exists both in favor and against the theory. Using the research into Alopecia X [a type of patterned hair loss] as an analogy for occult HAC, although occult HAC was originally thought to be due to sex hormone abnormalities, and although elevations in sex hormone concentrations were widely documented in dogs with Alopecia X, later research was unable to correlate elevations in any hormone with a clinical abnormality. The specificity of adrenal sex hormone panel testing needs to be carefully evaluated because evidence suggests that nonadrenal illness may commonly and nonspecifically increase sex hormone concentrations. Furthermore, not all dogs diagnosed with occult HAC respond to therapy directed at minimizing adrenal hormone secretion. Sex hormones may be elevated even further by therapy, yet dogs may improve clinically.

The possibility remains that ‘‘occult HAC’’ may exist as a syndrome, but one that is not caused by sex hormone secretion. Given the response of some cases of Alopecia X to therapy directed at hormone secretion, it is possible that local factors, such as enzymes, growth factors, or hormone receptors, may contribute to the hair cycle abnor- malities and be acted upon by substances secreted by the adrenal glands to manifest the clinical signs. The same could be true of occult HAC. For example, abnormal local tissue response to cortisol could cause the syndrome. Alternatively, occult HAC may represent the canine form of metabolic syndrome as seen in people and horses. Much work remains to be done to understand both the adrenal and local tissue contri- bution to the syndrome of occult HAC.

http://www.2ndchance.info/cushingsbehrend2010.pdf

In the absence of Bella's September test results, it is really hard for us to speculate as to the cause of her lethargy and weakness. It may certainly be the case that her Vetoryl dose was too high, especially since she is doing better now. But as far as the significance or impact of the elevated sex hormones, I would think they would only become an issue if her Cushing's symptoms rebound in the face of a cortisol level that is within recommended therapeutic range. In honesty, I don't think most clinicians would even recommend ongoing monitoring of intermediate hormones for dogs suffering from conventional Cushing's who are responding well to trilostane. It is an expense that would seemingly be of little value. If the intermediate hormones increase, you are only documenting a phenomenon that is expected to occur.

Marianne

[lulusmom]

Hi and a belated welcome to you and Bella.

I had two cushdogs, both passed, and both were treated with Lysodren, switched to Vetoryl and switched back to Lysodren. It's a long story so I'll spare you the details right now but wanted to say that I'm one of the member's Leslie mentioned as being an atypical cushing's skeptic. This is based on my own experience with the drug as well as science based research.

If a dog has naturally occurring typical cushing's, meaning a dog has a pituitary or adrenal tumor which is causing excessive production of cortisol, it is a given that sex/intermediate adrenal hormones will also be elevated. It is also a given that Trilostane, the active ingredient in Vetoryl causes an increase in some of these sex hormones. When I switched my little Lulu back to Lysodren, her IMS and I decided to wait until she was symptomatic again before loading her with Lysodren. It took over two months for her to become symptomatic again. We sent a blood sample to UTK during that time and when comparing the results to the first UTK adrenal panel before she was originally diagnosed, her sex hormones had drastically increased, yet she was totally asymptomatic until her post stimulated cortisol was well above 20 ug/dl. This correlates to studies done in otherwise healthy dogs treated with Trilostane for alopecia X. Despite increases in sex hormones, hair grew back and dogs showed no clinical problems with increased sex hormones. Pomeranians are known for their hormonal imbalances so I suspect a lot of them are walking among us with elevated intermediate/sex hormones and will live out their normal lifespan without any signs of atypical cushing's.

I have several questions which I've posted in blue text within the body of your post. I do this so I can stay organized in my thoughts and not miss something. I'm a very addled person capable of confusing members more than they already are. :o


Bella is 10 year old labradoodle, 70 pounds, diagnosed with Cushings in July of 2013, via ACT Stim test. The vet put Bella on 60 mg of Vetoryl. Within a few days Bella's excessive drinking and panting ceased and she returned to being more comfortable. With the exception of recurring bladder infections bella was fine until the middle of September.

Did your vet do a urine culture. Dogs with cushing's have very dilute urine and a regular urinalysis doesn't identify all of the white blood cells. A culture is done to identify specific bacteria so that an appropriate antibiotic can be given. If an appropriate antibiotic is not prescribed, the UTI will never resolve.

The vet believes (no confirmation despite seeing several different vets) that Bella went into an Addisonian Crisis.

Addison's is diagnosed via common symptoms associated with Addisons, ACTH stim test and routine electrolyte check. I see in your subsequent post that the acth stimulation test done at that time showed post stimulated cortisol to be above crisis level but no mention of check electrolytes. I believe Marianne mentioned that Vetoryl does affect aldosterone, which is the adrenal hormone responsible for keeping the body's sodium and water balanced. If aldosterone is too low, it throws off electrolytes and it can become life threatening.

With respect to symptoms commonly associated with Addisons, it appears that Bella really didn't have those symptoms. You mentioned in a subsequent post that your vet suspected Addison's when Bella became extremely weak in her back end and had trouble standing. If an acth stim test showed post simulated cortisol to be well above 1.5 ug/dl and electrolytes were normal, I personally would turn my attention to a common problem experienced, especially by larger dogs, being treated with Vetoryl. Dogs with uncontrolled cushing's are basically self medicating any inflammation in joints and the spine, as cortisol is a very powerful anti-inflammatory. Once treatment reduces cortisol, a dog will begin to feel the aches and pains of arthritis and it can be pretty severe, causing difficulty in mobility, weakness and lethargy. Did your vet rule out degenerative joint and/or spine problems?

Bella stopped taking the Vetoryl for a week and vastly improved although the symptoms of Cushings came back, excessive drinking, excessive urination, panting and generally uncomfortable. A week later Bella was put back on Vetoryl but at a much lower dose 30 mg.
Bella's blood was drawn and ACTH test done again and sent to University of Tennessee.

Was a routine acth stim test done first to determine if the 30mg dose was not effective before sending a blood sample to UTK? If not, I think the decision to have UTK do a full adrenal panel was premature. Others may have already asked you to post the results of the UTK panel so I'll just second that request.

She has had two tests done a month apart at the University of Tennessee. The university has recommended taking Bella off the Vetoryl and switching to Lysodren. The recommendation is Bella to be off of the Vetoryl for 30 days before starting the Lysodren. I am worried about managing symptoms for 30 days - excessive drinking/urination being the symptom so hard to manage in a large dog.

Again, unless Bella was symptomatic and your vet ran an acth stim test and confirmed that pre and post cortisol was within the therapeutic range of 1.5 ug/dl and 5.5 ug/dl, I'm not sure an adrenal panel was necessary. Your help in clarifying what was going on with Bella when the various tests were done would put a lot of pieces of the puzzle together.

Bella also takes soloxine (thyroid/hormone medication, once a day)

I don't know how long ago Bella was diagnosed with hypothyrodism but a good number of dogs with cushing's will have low thyroid values at diagnosis. This does not mean they have primary hypothyroidism...it means that high levels of cortisol transiently effect thyroid hormones which normalize once the underlying cause (cushing's) has been addressed. This temporary condition is called sick euthyroid syndrome (SES). If Bella does't have primary hypothyroidism, Vetoryl may have normalized thyroid function, negating the need for soloxine. If that were to be the case, soloxine supplementation could be the cause of Bella's continued excessive drinking and peeing. Those are classic symptoms of "hyper"thyroidism caused by oversupplementation of thyroid hormone. if you haven't had Bella's thyroid checked, that's the first think I would do.

Amlodopine (blood pressure medication, once a day) and 6 mg melatonin twice a day.

When your vet discovered that Bella's blood pressure was high, what was going on with her at that time. Did your vet know if cortisol levels were where they needed to be? If they were, did he suggest an abdominal ultrasound to rule out an adrenal tumor. The results of the LDDS test you posted indicate Bella has pituitary dependent disease but on rare occasions a dog can also have an adrenal tumor which can be the root cause of hypertension. Again, not having a good understanding of timelines, tests done, symptoms when tests were done, etc., it's difficult to wrap my head around your vet's rationale.

Did anyone else in the group have to switch their dog from vetoryl to lysodren?

As I mentioned above, I am very familiar with both drugs and switching from one to the other. In my personal opinion based on the information you have provided so far, I would not switch to Lysodren based solely on elevated intermediate/sex hormones.

i am hoping you can have your vet give you copies of all testing that has been done on Bella since she was diagnosed with cushing's. If she was diagnosed with hypothyroidism before cushing's, can you please get a copy of the whatever test your vet did to confirm the diagnosis? We always recommend that members keep a folder with all vet records. They come in real handy should Bella ever need to go to an ER. Attending vets are very happy to have a dog's medical history at their fingertips. I'd like to say that as an educated pet owner I could provide whatever information the attending vet may need to know but when you are in crisis mode, 90% of what you thought you knew flew out the window before you got into the car. :) Those files also come in handy when us nagging members keep asking you to post test results. :D

Sorry for the really long post but there's lots to talk about, lots to share and lots to understand about Bella's particular history.

Glynda

[molly muffin]

Hello and welcome from me too. :)

In addition to the really great info that and questions asked already, I would just add, and this goes along with cortisol self medicating masking other problems, like joint, spine, etc, is that every dog is different and while Bella might not have been addisons, it very well could be that she will do better with her cortisol post number being a bit higher. This is quite common when the cortisol goes low and the joints and other aches start to act up.

Sharlene and Molly Muffin