Frito needs your help (11 y/o Yorkie) Vetoryl

[scrisp]

Hi Folks,

Frito is an 11 year-old Yorkie, who has been diagnosed with Cushing's and is being treated with Vetoryl. Frito weighs around 10 lbs (down from a high of 14 lbs), and feels a little "boney" (e.g., you can feel his spine).

At first, treatment seemed to be working great. His fur as totally regrown in the symmetrical areas were he had gone bald, and his coat looks thick and healthy. He also seems pretty happy and energetic. And both of those remain true today (treatment began on 4/21/11).

But here is the problem. He continues to drink lots of water. With no restrictions, he drinks around 6-7 cups of water per day. If we limit his water, he is still drinking about 4 cups per day. As you might imagine, he is peeing constantly; every hour or two, including throughout the night (and some accidents in the house). So my wife and I are not getting much sleep ;-)

We have slowly increased his Vetoryl dosage incrementally from 10mg to 60 mg in 10mg increments. He was able to tolerate each increase no problem, but without any change in his thirst. Finally, we added another 30mg (for a total of 90mg/day for this little guy), and he is still tolerating but it is not working, that is, reducing his thirst and peeing. His appetite remains quite strong (voracious).

So my question is -- does this mean we have the wrong medicine and need to try something different? Obviously the Vetoryl initially made a huge improvement with his fur. But it has not addressed his thirst and hunger. Looking for your suggestions.

Also, I know you all like test results ;-) I have requested the initial blood test results from his initial diagnosis, but I don't have those yet. Instead, here are his last two urine analyses, if they are helpful:

12/20/12 (when taking 30 mg/day):

Creatinine (U) (Jaffe) 160 mg / l 1414 micromol / l
Protein, total (U) <40 mg / l
Cortisol (urine) 4.5 mg / dl
Protein / creatinine ratio (K-value) 0.25 <0.50
Cortisol/Creatinine-Quotient (U) 88.6

1/12/12 (when taking 50 mg/day):

Creatinine (U) (Jaffe) 170 mg / l 1503 micromol / l
Protein, total (U) 28 mg / l
Cortisol (urine) 4.7 mg / dl
Protein / creatinine ratio (K-value) 0.16 <0.50
Cortisol/Creatinine-Quotient (U) 86.1

Thanks in advance for any advice and suggestions,

Steve Crisp

[labblab]

Dear Steve,

Welcome to you and Frito! I see you have posted urinalysis results, but I am instead looking anxiously for monitoring ACTH blood testing results. While the UC:CR urine test is used as an initial diagnostic screening tool for Cushing's, it has very limited and circumscribed value in making determinations regarding dosing changes once treatment has begun. Blood measurements of cortisol levels are an absolute necessity in determining the effectiveness and safety of any given dose of trilostane. Have any monitoring ACTH stim tests been performed since Frito started his treatment? I do have to ask, is your vet aware of this huge dosing increase?

At a dosing formula of 9 mg. per pound (90 mg. for a 10 pound dog), I must tell you that in my eight years of participation on Cushing's forums, Frito is probably receiving the highest relative dose of trilostane that I have ever known a dog to be given. :eek: :eek: In honesty, I am absolutely amazed that he is acting normally (and even still standing!) on a dose of that size -- which actually leads me to question the effectiveness of the medication you are giving him. Can you tell us what form the Vetoryl is in (is it capsules or liquid?). By any chance, is the drug beyond its expiration date?

Also, it may be the case that it is another issue altogether that is causing the excessive thirst and urination -- for instance, diabetes or kidney problems. In that event, the Cushing's medication will not solve the problem, regardless of dose. If you can give us the "normal" ranges for Frito's urinalysis results, that will help us with assessment of any related abnormalities. But again, in addition to the results of a urinalysis, it is also blood testing that is critical in identifying other problems that may be causing these symptoms for Frito. And it is also testing of blood chemistries that ensures that the Vetoryl is not creating any physiological imbalances that can lead to life-threatening problems. So please do let us know what additional testing has been performed for Frito.

Sorry for so many questions in response to your first post, but your answers will help us move forward in our problem-solving.

Marianne

[Squirt's Mom]

Hi Steve and welcome you, your wife, and Frito! :)

I, too, am flabbergasted Frito is functioning period on such an incredibly high dose much less that his thirst hasn't decreased. :confused: Something is hinky in Fritoland and seeing those tests results will help us a great deal in helping him and ya'll. That is absolutely amazing! :eek:

We will do all we can to help you learn about Cushing's and other conditions that can muddy the waters. Ya'll do not walk this path alone; there is a whole crowd walking beside you now, all you gotta do is reach out.

I am still blown away that Frito hasn't had a crisis on such a huge dose for such a little guy! That has got to be one tough little pup!

Hugs,
Leslie and the gang

[scrisp]

Thanks for the quick replies.

The medicine is very fresh. It is in tablets with powder inside.

I concur with your conclusion that the medicine must not be working at this point given the very high dosage.

The odd thing is it worked from the beginning in having his fur come back.

Anyways, I should have his initial test results tomorrow I hope and I will post them.

He has also been tested for diabetes, and that came back negative.

Would either of you advise just stopping this high dosage? Reducing it? Or waiting until another blood test can be taken?

Thanks much again for your quick assistance,

S-

[Cyn719]

Welcome Steve, your wife and Frito

Welcome to the forum....Frito is adorable!!

You have come to the right place as you can see. You already have members who are here to help. Hang in there it's a lot as you know ...but everyone here is so nice and so knowledgeable!! You will get lots of help and support for sure!! :)

[labblab]

Steve, I've only had a moment so far to look at Frito's blog, but it is clear that he is a well-loved little boy!! :o :)

Since beginning treatment, can you tell us if your vet has performed any ACTH blood tests to monitor the use of the Vetoryl? If so, how recently? And what are your vet's thoughts as to what is going on with Frito?

Marianne

[scrisp]

Since beginning treatment, can you tell us if your vet has performed any ACTH blood tests to monitor the use of the Vetoryl? If so, how recently? And what are your vet's thoughts as to what is going on with Frito?

Marianne

His last blood test was on 10/12/11 and all I show in my records was that it was positive and indicated an increase in dosage was needed. At that time he was taking 20mg/day and was increased to 30mg/day. Since then, he has received three urine tests to check his cortisol levels and adjust his dosage (upward).

I have requested the blood test results, so hopefully I will have them tomorrow evening.

As for Frito's blog -- thanks. I suspect he is one of the most photographed dogs in the world ;-)

[jmac]

Hi Steve,

I just wanted to stop by to welcome you and Frito; he sure is a cutie! I don't have any experience with Vetoryl or any other medications except Anipryl because my dog has such minor symptoms. I am glad you got some good advice from other members though. You have definitely found a wonderful place with helpful, caring, concerned people. They will guide you to do the best you can for little Frito.

Julie & Hannah

[Cyn719]

Great blog!!!:):)

[labblab]

Steve, I am back now with a link and a quote that explain why I feel so worried that Frito's Vetoryl dose has been increased on the basis of UCCR (urine) testing alone. Here's the summary of a 2009 research study found by another one of our staffers, Lori:

Urinary Corticoid : Creatinine Ratios in Dogs with Pituitary-Dependent Hypercortisolism during Trilostane Treatment (http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0374.x/abstract)


Conclusion and Clinical Importance: The UCCR cannot be used as an alternative to the ACTH stimulation test to determine the optimal dose of trilostane, but might be helpful in detecting dogs at risk for developing hypocortisolism during trilostane treatment.

If you check out the link above and read the more complete study summary, you will understand why the authors advise against using the UCCR as the basis for dosing increases. Of course, our biggest worry for Frito is whether this high dose of Vetoryl is actually an "overdose" for him. And per this study, perhaps his UCCR can actually be somewhat helpful in that regard. If you can give us the "normal" reference range for his listed "cortisol/creatinine quotient" (UCCR) results, it will be easier for us to assess them, particularly if you live outside the U.S. where the units of measurement in this test may differ. But most importantly, even if any conclusions can be drawn from those results, they do not reflect the safety of Frito's condition since the final whopping big dosing increase. How long has he been taking the 90 mg.?

I am not a vet, but I am very worried about the size of this dose and the apparent lack of symptom resolution other than his coat, both of which raise so many question marks as to the real source of Frito's problems. I think we may ask, does he even have Cushing's at all? Apparently there are studies that have shown that normal dogs without Cushing's who are given Lysodren (an alternative to Vetoryl) actually appear to be more resistant to the drug's effects than are dogs with the disease. Perhaps the same thing may hold true for Vetoryl (trilostane).

If Frito were my dog, I would ask that an ACTH blood test be performed immediately, along with testing of his complete blood chemistries and cell counts. If this testing cannot be done right away, I would definitely decrease his Vetoryl dose significantly, and perhaps even halt it altogether until you can get things sorted out. Frito's situation is way out of the ordinary, suggesting that something very important is either being overlooked or mistaken.

Marianne

[scrisp]

I appreciate the feedback and your suggestions. In an airport now and will have to be quick.

I will read the link when possible, and think your recommendation is good advice. I've sent that information to my wife who is home with Frito.

Glad to have found you all -- now hopefully we can get a correct diagnosis (if that is the issue), or alternative treatment.

Appreciate the inputs.

S-

[Squirt's Mom]

Hi Steve,

In answer to your question about stopping the Trilo - if it were me, I most certainly would. First, he is on a massive dose for a pup his size putting him at risk for an Addisonian crisis or worse. Second, it apparently isn't working for him so why add chemicals to a system when those chemicals aren't doing what is expected? Third, this is a drug that typically works miracles for cush pups so I would have to question the Cushing's diagnosis at this point and would want in depth testing to make sure nothing else is happening to cause the signs you are seeing. Fourth, the testing that has been done to check his cortisol levels aren't the tests that are needed to determine this so the results are questionable at best.

Is Frito seeing an IMS? If not, I would recommend you seek one out. He may be one of our mystery pups and would need the expertise of a specialist on his side. Has he had an abdominal ultrasound? If not, I strongly suggest he have one. As one of our mods says, this test "gives the biggest bang for the buck". Ultrasounds saved my Squirt's life by finding a tumor on her spleen - which was also causing false-positives on her Cushing's testing. ;)

Wishing you safe travels!
Hugs,
Leslie and the gang

[Cyn719]

I agree with the experts. I would have to stop the meds. You have great advice from the members here- but I just have to add my two cents and say my 85 lb dog Penny was on 60 mg of Vetoryl then 120 and she crashed. Let me tell you it was the members here who got me to stop it and glad I did -- Penny went into Addisionians and it was scarey. Every dogs situation is different but Frito is only 10 pounds -- it doesnt seem possible that he could handle this much medication. Will be back to check in ---

Give that little guy a Big hug!!

[scrisp]

Thanks again for the feedback. We agreed and have stopped the meds for now.

We will visit our vet tomorrow and pick up the previous lab results, and see about another blood test. I will post those earlier reports as soon as I get them (they were not successful trying to fax them to me).

Frito is rather "antsy", still drinking, peeing, and had an accident inside while we were here. We are really hoping to get a better diagnosis or treatment plan established for him.

Thanks for everyone's time and support.

S-

[scrisp]

One more thing ... if anyone has specific suggestions of what I need to ask my vet, or what specific tests Frito should have done, I am all ears and happy to suggest those to my vet.

Appreciate it (in advance),

S-

[labblab]

If you would actually be able to schedule an ACTH stim test within the next 24-48 hours, you may NOT want to stop the Vetoryl (at least not completely) until the blood draw has been completed. Theoretically, trilostane exits the system within 24 hours and so an ACTH stim test conducted several days after cessation of dosing will not give you an accurate picture of the therapeutic effectiveness of the drug as you were giving it. It might be really informative to see where his cortisol level is on that huge dose!

Having said that, of course Frito's health and safety is the most important concern. So if he acts as if he is being overdosed with the drug (lethargic, vomiting, nausea, trembling), you would want to stop it immediately, no matter what. And if the ACTH stim testing can't be performed immediately, probably the safest thing is to just halt the medicaton. Also, I'll stop back later to talk some more about diagnostic testing in the event that you do want to completely start over.

Please tell us how long he has been taking this highest dose, and have you noticed any changes at all in his behavior during this time, for the worse as well as for the better?

[scrisp]

Thanks for that thought. Frito didn't have his second pill this evening, which is 60 mg.

He has been taking 90 mg probably since February 6th, and there have been no adverse affects that we can detect. That was an increase over 60 mg which he had been taking since January 22nd.

We can give him his 60 mg before bed if you think that makes the most sense. It won't be any problem for him either way.

Please advise -- I will try to have him get the blood test tomorrow at the vet. Can you remind me -- what prep is needed (e.g., no food in morning)?

Appreciate this and all inputs.

S-

[labblab]

From the info you've given us, I've tried to put together this dosing history:

Started treatment 4-21-11 at 10 mg. ?
At some point was increased to 20 mg.?
Remained on that dose until 10-12-11 when it was increased to 30 mg.?
At some point between October and December was increased to 40 mg.?
1-12-12: Increased to 50 mg.
1-22-12: Increased to 60 mg.
2-06-12: Increased to 90 mg.

Is this history correct? If so, this is absolutely a massive dosing increase in an extremely short amount of time, especially without the necessary blood testing. Given this new info, no, I would not give Frito any more Vetoryl and I would still press your vet to have the ACTH stim test performed tomorrow, along with testing of his blood chemistries. I think both of those two tests are essential for Frito's safety. Check with your vet in the morning to see whether they prefer him to be fasted for the blood chemistries. If he were to be dosed with Vetoryl, he should have breakfast along with the medication, and the test performed 4-6 hours after dosing. But if he is not given any more Vetoryl, a fasted test may be preferred.

Steve, I must ask again whether your vet instructed you to make this huge dosing increase within the last eight weeks? If so, it is absolutely contrary to the recommendations of the drug manufacturer, and it worries me tremendously as to the knowledge and experience of your vet. I will go so far as to say that the risk to Frito is really unforgivable, and I would search immediately for a new vet. Here is a link to the U.S. Product Insert for Vetoryl. Once you read through it, I think you will understand why we are so worried about Frito being placed on this huge increase in such a short time without any of the essential monitoring tests:

http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf

Marianne

[scrisp]

Well, that's close. Let me try to recreate from my e-mail traffic with the Vet:

Started treatment 4-21-11 at 10 mg (see diagnosis test below)
5-1-11: Increased to 20 mg since no improvement
5-31-11: Stayed at 20 mg since blood test showed good levels (see below)
6-25-11: Stayed at 20 mg in spite of Cortisol-creatinine ratio (see below)
10-23-11: Increased to 30 mg based on urine test results. Note, a couple weeks prior to this increase is when he started drinking and peeing excessively, including inside the house for the first time. He has not slept through the night since.
12-20-11: Increase to 40 mg based on urine test results
1-12-12: Increased to 50 mg based on urine test results
1-22-12: Increased to 60 mg based on no improvement
2-06-12: Increased to 90 mg based on no improvement

I did find some of the blood test results. I will include them in a subsequent post since they are hard to read.

Thanks for your help. Oh, and I did give him his 60mg pill just before bed (and before your e-mail). So I will plan to fast him with no more meds tomorrow prior to the blood test.

S-

[scrisp]

Here are the blood tests I referred to above.

These are the Cushing's diagnosis test results on 4/20/11 (this was when we had to bring Frito in three times for blood draws). Please note this is a Google Translate from German to English, since we are currently living in Germany, and there were some typos or OCR errors in the original file:

materials
Serum (S)
General patient data
age
11 years
endocrinology
Dexa.Screen. test
(low dose), 3-state.
Interpretation of low-dose dexamethasone test (dog / cat)
First normal adrenal function:
normal basal and Suppressionswert <0.3 ug / dl
after 3-4 and 8 hours
Second hyperadrenocorticism:
normal or erhhter basal value and
Suppressionswert> or = 1.5 mg / dl
(cats> 0.5 mg / dl) after 3 and 8 hours
Suppressionswerte between 0.3 and 1.4 in the dog
bed ¸ ‰ rfen another Abkl tion.
(possibly ACTH stimulation test)
Cortisol 7.2 74 mg / dL 0.5-6.0
nmol / l 14-166
Cortisol (serum 2) <0.3 <8 g / dl
nmol / l
Cortisol (serum 3) 0.5 14 ug / dl
nmol / l


Also, here is his next blood test results from 5-31-11:

Geriatric profile
T4 (total thyroxine) 0.8 - (1.0 - 4.0) ug / dl
Kidney:
Urea-N 9.8 (9-29) mg / dl
Creatinine 0.6 (<1.4) mg / dl
Sodium 149 (143-156) mmol / l
Potassium 5.1 (3.9 - 5.8) mmol / l
anorg.Phosphat 1.4 (0.9 - 1.7) mmol / l
Liver:
Total bilirubin 0.11 (<0.3) mg / dl
ALT (GPT) 120.2 (<122) U / l
Alk phosphatase 186 + + (<147) U / l
y-GT 20 + + (<13) U / l
AST (GOT) 34.4 (<59) U / l
GLDH 15.6 (<18) U / l
Total protein 6.2 (5.5 - 7.3) g / dl
Serum albumin 3.85 (3.1 - 4.6) g / dl
Globulin 2.4 (1.6 - 4.1) g / dl
Pancreas:
Glucose 82.9 (57 - 126) mg / dl
a-amylase 510 (<1264) U / l
Lipase 124 (<298) U / l
Cholesterol 194 (<398) mg / dl
Cholesterol (sober normal weight dogs): <300 mg / dl
Fructosamine 200 - (203 - 377) pmol / l
Muscle:
CK 49 (<378) U / l
LDH 41 (<159) U / l
Calcium 2.6 (2.1 - 2.9) mmol / l
Magnesium 1.0 (0.7 - 1.1) mmol / l
Total triglycerides 267 (28-468) mg / dl
Triglycerides (normal weight dogs sober): 28 - 150 mg / dl
Blood count
Leukocytes 7.4 (6-12) G / L
Erythrocytes 7.42 (6-9) T / l
Hemoglobin 16.5 (15-19) g / dl
Hematocrit 46 (38-55)%
MCV 61 (60-77) fl
HbE 22 (17 - 23) pg
MCHC 36 + (31 - 34) g / dl
Platelets 277 (150-500) G / L
Differential blood count
Basophils Gr. 0 (0 - 1)%
Eosinophilic Gr. 7 + (0-6)%
Polymorphonuclear 57 (55-75)%
33 + lymphocytes (12-30)%
Monocytes 3 (0-4)%
Basophils Gr. (Absolute) 0 / ul 3)
Eosinophilic Gr. (Absolute) 550 (0 - 600) / ul
Polymorphonuclear (absolute) 4228 (3000 - 10000) / li
Lymphocytes (absolute) 2430 (1000 - 4000) / ul
Monocytes (absolute) 223 (0 - 500) / ul
atypical cells 0 (0)
Variations in size 0 (negative)
Polychromasia 0 (negative)
Cortisol 2.6 (0.9 - 4.5) ug / dl

Finally here is his next blood test on 6-25-11:

Cortisol 4.1 (0.9 - 4.5) ug / dl
(ECLIA)
Thyroid Profile 1
T4 (total thyroxine) 1.2 (1.0 - 4.0) ug / dl 1)
(EIA) 1)
Free thyroxine 0.7 (0.6 - 3.7) ng / dl
(ECLIA)
TSH (canine) 0.11 (<0.5) ng / ml
(CLIA)
Cortisol-creatinine ratio 189.4 + + (<33) 2)
Normal value <33
Gray area (check recommended) 33-50
Hyperadrenocorticism be> 50
Cortisol in urine (CLIA) 880.0 ug / l
Creatinine in urine 145.1 mg / dl
Protein / creatinine ratio <0.1 (<0.5)
101 protein in the urine (60 - 530) mg / l
Note:
1) A decreased T4 concentration indicates hypothyroidism, but can
also by non-thyroidal illness (NTI) or by the administration of certain
Drugs may be limited. Occasionally, hypothyroid dogs in values
have lower reference range.
In dogs with clinical symptoms and a decreased or low
normal T4 concentration is recommended to confirm the diagnosis
Determination of canine TSH.
A T4 concentration above the reference range for healthy dogs can
. occur It is u.U. conditioned by T4 antibody, as these in the assay
be observed. In this case, we recommend the determination of free T4
the dialysis procedure.
An increase of T4 as a result of malignancy in dogs
rare.
In dogs lying in the thyroid hormone supplementation
T4 concentrations 3-6 hours after drug administration in the upper or low
above the reference range.
Please note that the reference ranges based on updated
Data have been adjusted.
2) The cortisol / creatinine ratio is above 50 (pathologic range). The
Specificity of the assay is approximately 70 - 75%, ie a positive test result
should always be associated with the clinical presentation and other
laboratory parameters are evaluated. To confirm the diagnosis
We recommend the implementation of a low-dose dexamethasone Suppressionstests
(LDDS) or an ACTH stimulation test.

[labblab]

Steve, I've only had the chance to quickly review the tests, and so I need to go back and look at several things in more detail. But this is what I see so far.

It looks as though the initial diagnosis was based on the results of a LDDS test (low dose dexamethasone stimulation test). This is a test which requires three blood draws. Unfortunately, I'm having trouble sorting out the numbers that have been given for Frito, so I can't comment on the results. This is perhaps a problem with the Google translation. Was this the only test that was conducted prior to starting Frito on the Vetoryl?

I do not see evidence that any ACTH stimulation tests have ever been conducted, either as an initial diagnostic tool or to monitor the effect of the Vetoryl. I do see some baseline (or "resting") cortisol levels. Some recent research in the U.S. suggests that baseline cortisols may have value in assessing the effect of Vetoryl. But more research is needed, and baseline cortisols are not considered to be either a sufficient or adequate substitute for ACTH stimulation testing throughout the entire course of treatment.

I do see the repeated UCCR urine tests (cortisol/creatinine ratio). However, the laboratory's description of the test corresponds with what we've already been saying -- it is considered to be an initial diagnostic test for Cushing's that must be validated by a subsequent blood test such as the LDDS or ACTH. It is not a test for monitoring treatment.

Given this history, I am now doubtful as to whether your vet will even be able to administer the ACTH stimulation test tomorrow. It requires a special stimulating agent which they may not even have on hand, since I see no evidence that Frito has ever had the test done in the past. I do not know if there is an issue with conducting this test in Germany.

Please bear in mind that I am not a vet, and so it is really not my place to tell people to give or withhold medication. But if your vet is not capable of performing an ACTH test, I do not understand how they can safely treat a Cushing's dog. And the massive dosing increase still seems inexcusable to me under any circumstance, but especially so when based solely on lack of improvement. I also have to question the accuracy of the initial diagnosis if it was based only on the result of that single LDDS test. Cushing's is a very tricky disease to diagnose, and ought to be supported by multiple indicators.

I must go for now, but hopefully other folks will also be stopping by to take a closer look at those lab values.

Marianne

[SasAndYunah]

Hi Steve and Frito,

a Dutch neighbour here :) It's the middle of the night for me so I won't comment extensively but will explain a few things, the best I can...

I understand the worries of the other members here about not having had an ACTH test done but...I must say that here in The Netherlands, but also in Germany I suppose, the UC:CR test is done to measure cortisol levels. It's not only used as a test to exclude possible Cushing's. There's a huge difference in how Cushing's is monitored between the USA/Canada and Europe. But, I must say that in order to use the uc:cr test to monitor cortisol levels, you need at least 3 urine samples on three days in a row. So just the one urine sample is not enough, it needs to be a 3 day sample period.

I am too tired to find the study that says it's perfectly okay to monitor this way...in fact, here (in The Netherlands) they actually seem to think it's even better since it is so much less invasive, less stressful and even more accurate since the cortisol levels in the urine are more "consistent" then the cortisol levels in the bloodstream....that's more fluctuating.

Having said all this, I am somewhat worried about the extreme dose of Vetoryl and the lack of resolving symptoms like excessive drinking/peeing. Was Frito ever tested for DI? (diabetes insupidus).

But to all the USA and other members, uc:cr testing to monitor cortisol levels is the norm here...and not a lack of knowledge (if the testing is done right) just a differant approach :)

Saskia :)

ps I think Glynda also has the thesis from the unversity of Utrecht (in english) where the uc:cr testing is explained and compared to other methods of testing (like the ACTH). But I will look tomorrow for it and post it here... :)

[lulusmom]

I do have a thesis that Saskia referred to me and I'm still making my way through it, slowly but surely. It's really massive. I'm not sure this is the same study she is referring to because I can't find anything in it that indicates that a UCCR can be used to determine optimum trilostane dosing, whether one day or three day collection. The studies in this paper say that it cannot be used for that purpose. See below:


The results of this study indicate that the UCCR cannot be used as an alternative to the ACTH stimulation test to determine the optimal dose of trilostane. In most dogs with PDH included in this study, UCCRs remained above the upper level of the reference range for at least 2 months after receiving the optimal dose of trilostane. The UCCRs also did not correlate with the post-ACTH plasma cortisol concentrations and thus the UCCR cannot be considered a reliable indicator of treatment control. Similarly, UCCRs also cannot be used as an alternative to the ACTH stimulation test in dogs in which mitotane is used to partially destroy the adrenal cortex (Randolph et al. 1998, Angles et al. 1997). In contrast, the UCCR is a reliable indicator of persisting cortisol secretion after hypophysectomy or nonselective destruction of the adrenal cortex by mitotane therapy (Meij et al. 2002, Den Hertog et al. 1999).

The discussion points of this study closed by saying:


In conclusion, the results of this study demonstrate that the UCCR cannot be used to determine the optimal dose of trilostane, but could be helpful in detecting dogs that are at risk of developing hypocortisolism during trilostane therapy.

There were several paragraphs which discussed this but in the nutshell, there was a definite pattern in the UCCR indicating hypercortisolism in dogs who had already been stabilized on an optimum trilostane dose.

I also noted that Dechra, the manufacturer of Vetoryl, had a special acknowledgment stating that they supported the study.

I hope this helps.

Glynda

[labblab]

Hmmm...now I'm really confused. I'll be really anxious to see Saskia's reference paper tomorrow. I've known that three-day urine samples, in conjunction with dexamethasone tablets, have been an accepted (even preferred) Cushing's diagnostic in Europe. But I'm really surprised to hear about UCCRs being used for monitoring, especially in light of this "Update on Trilostane" published by Ellen Behrend just last summer and offered by Dechra as a continuing education resource. It surely does not give the impression that UCCRs are yet an accepted monitoring method.

http://www.dechra-us.com/Files/dechraUSA/downloads/Case%20Studies/Clinicians%20Brief-trilostane.pdf


UCCR & Monitoring

● An early study found that the urine cortisol:creatinine ratio (UCCR) before administering trilostane could be an indication of duration of action, but 2 later studies yielded conflicting results.2,5,13
● Interestingly, in one report of 6 dogs that had UCCRs within the reference range “most of the time,” 3 developed hypocortisolism (Addison's disease) and hypocortisolism was suspected but not confirmed in the other 3 dogs.13

Further research is needed to determine whether UCCR will prove useful as a monitoring tool.

[scrisp]

You folks are all very kind to provide your time and insights. I understand that the history I've provided, and the language translation issues can be quite confusing.

Also, let me clarify, the last two dosage increases (from 50mg to 60mg and from 60mg to 90mg were my own doing -- not the vet's recommendation). It was based solely on the fact that the lower treatment wasn't working, and I was trying to determine if it could be the dosage level or not.

Obviously, I have now concluded it is not the dosage level. So I will, following whatever testing can be done at the vet today, either lower the dosage back to 30mg, or stop it all together while we regroup and figure out what is exactly causing Frito's excessive thirst and peeing, shaking, and general nervousness.

To answer another question, yes, the vet did perform a test for diabetes pretty early on in this process, and found no evidence for it.

Once again, thanks to all that have taken the time to read though my somewhat confused history and share your collective wisdom. Will let you know what I hear from the vet today (and after any lab results are back).

S-

[SasAndYunah]

Glynda,

yes that was the paper I was reffering to :) And the part I had in mind is:

"The effectiveness of trilostane therapy is judged by resolution of clinical signs associated with glucocorticoid excess and results of an ACTH stimulation test (Neiger et al. 2002, Ruckstuhl et al. 2002). The aim of performing an ACTH stimulation test in a dog on trilostane therapy is to evaluate whether sufficient adrenocortical reserve is present at the time of maximal effect of trilostane, which is 2-3 hours after administration (Neiger and Campbel 2001). The disadvantages of the test are that: (1) it only provides information about suppression of cortisol production during a short interval, (2) it is invasive, (3) the post-ACTH cortisol concentration thought to indicate optimal dosage of trilostane is still arbitrary, and (4) there is concern about the availability and cost of the injectable ACTH (Peterson 2004) required for the test.
The urinary corticoid:creatinine ratio (UCCR) provides an integrated measure of corticoid production over a given interval, thereby overcoming the problem of fluctuations in plasma concentrations (Rijnberk and Wees 1988). It is useful not only in the initial diagnosis of hypercortisolism but also in detection of persisting cortisol secretion after hypophysectomy or nonselective destruction of the adrenal cortex by mitotane therapy (Meij et al. 2002, Den Hertog et al. 1999). Because the UCCR is an integrated measure of glucocorticoid production, it might be a more appropriate indicator of the therapeutic efficacy of trilostane than an ACTH stimulation test. In addition, it requires less time and is not invasive."

But on closer examination, this part is leading up to the study done to determine if the uc:cr would be an appropriate tool...and is you stated Glynda, it is not :)

So I appologize for adding to the confusion :rolleyes:

Saskia :)

[labblab]

Sas, thanks so much for checking back in and clarifying! And Steve, I am VERY relieved to know that your vet did not tell you to increase Frito's dose so massively!! However, that does not relieve us of the issue of inadequate monitoring, which I still think you must address with your vet. Are you limited as far as veterinary options, or can you check with other vets in your area to see how they care for Cushing's patients?

As far as Frito's initial diagnosis, what symptoms led you to suspect Cushing's in the first place back last spring? I know you've spoken about skin/coat problems, but how about any other problems at that time? You noted in your earlier summary that it was around mid-October that Frito started drinking and peeing excessively. Was his thirst/urination normal prior to that? Other typical Cushing's symptoms are voracious appetite, excessive panting, seeking out cool places to lie, pot belly, lethargy, and loss of muscle mass leading to hind end weakness. Are any of these problems that you saw at the time of diagnosis, or subsequently?

Regarding Frito's thyroid status...I see that his T4 was below normal on his 5-31 geriatric panel. I'm guessing this prompted the more thorough evaluation of his thyroid status that was later performed on 6-25. The second testing resulted in T4 values that were in the normal range this time, but low normal. By that time, I believe Frito had been taking the Vetoryl for a couple of months. Cushing's is a disease that can prompt secondary thyroid issues, so for some Cushpups, previously low thyroid values will improve once the Cushing's is well controlled. And although I may be wrong, if hypothyroidism is deemed a problem for Frito, I think his June profile would be consistent with it being secondary to another illness. But hypothyroidism itself can definitely cause skin and coat problems, and that is partly why I am wondering whether that was Frito's chief complaint last spring. Have your vets commented at all re: his thyroid status?

Sorry for so many additional questions, but your answers will be very helpful to us. Also, if you can, please clarify Frito's actual numerical result on that first diagnostic LDDS, as well as the range that would be considered "normal" by that laboratory.

Marianne

[Cyn719]

Was just catching up on Frito ..good luck at the vet.

[Squirt's Mom]

Hi Steve,

I would like to point out that there are two types of diabetes. DM, or diabetes mellitus, is the common form that we think of when we think of diabetes. It is a disease of high blood sugars. The other form of diabetes is rare and is not related to blood sugars but rather how the pup processes water; a matter of water imbalance in their system. This form is called Diabetes Insipidus and cannot be tested via blood work. So unless Frito underwent water deprivation testing or testing via the meds used to treat DI to see if it worked or not, DI has not been ruled out and is definitely a possibility based on Frito's signs and lack of response to the massive dose of Trilo he has been on.

Here are some links about DI for you, and your vet if needed.

• Polyuria, Polydipsia and Diabetes Insipidus
http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2002&PID=2556

• Diabetes Insipidus
http://www.petplace.com/article-printer-friendly.aspx?id=3258

• Diabetes insipidus
http://www.provet.co.uk/health/diseases/diabetesinsipidus.htm

• Diabetes Insipidus
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40507.htm

• Desmopressin acetate (brand name DDAVP®)
A synthetic antidiuretic hormone that is used to treat Central DI
http://www.petplace.com/drug-library/desmopressin-ddavp/page1.aspx


Hang in there!
Hugs,
Leslie and the gang

[scrisp]

You folks deserve kudos for your patience ;-)

So we went to the vet this morning, but did not have any blood tests done. He pointed out if we want to have the ACTH test, we should plan to do that next week, when we have a day to devote to it (and not on a weekend).

But we also reviewed all of his previous lab results, and our vet does not know what the next step should be given his history and considering we have already tried higher Vetoryl doses.

So I am very interested in any suggestions as to other causes/treatments for the excessive thirst/peeing, shaking, and skittishness (all of which I associate with Cushings). Also, if a different medicine might be better, I'm open to hear that, but my vet did not think so.

Reading over some of your other posts on this forum, I got the impression that you might benefit from his previous lab results. I now think I have them all, but doubt you want me to include all of them. Don't know if you have a place to put a PDF file on the site and link to it. So instead, below are the dates and any results that were off-nominal (with + or - for high or low, and normal levels in parentheses). Hopefully this is helpful to those of you that are diagnosticians ;-)

(Once again, these are Google translations of German, so sorry for any thing that is unclear.)

3-12-2009 (before Cushings symptoms)

Kidney: Urea-N = 9.1 - (10-25) mg/dl
Liver: Alk. phosphatase = 150 + (<92) U/l
Liver: serum albumin = 2.94 -- (3.2-4.7) g/dl
Pancreas: lipase = 1335 ++ (<300) U/l
Pancreas: cholesterol = 351 + (108-300) mg/dl
Muscle: LDH = 162 + (<100) U/l
Muscle: triglycerides, total = 731 ++ (50-100) mg/dl
Blood count: MCHC = 37 + (31-34) g/dl

3-4-2010 (very sick with E-coli)

Liver: y-GT = 11 + (<6) U/l
Pancreas: glucose = 121 + (54-100) mg/dl
Muscle: CK = 356 + (<180) U/l
Muscle: LDH = 221 + (<100) U/l
Blood count: Erythrocytes = 9.62 + (6-9) T/l
Blood count: Hemoglobin = 21.3 + (15-19( g/dl
Blood count: Hematocrit = 58 + (38-55) %
Blood count: MCHC = 37 + (31-34) g/dl

2-15-2011 (test for Rabies antibodies prior to travel)

Cortisol-creatinine quotient 113.7 ++ (<33)

5-31-2011 (blood work for Thyroid)

T4 (total thyroxine) = 0.8 -- (1.0-4.0) ug/dl
Liver: Alk. phosphatase = 186 ++ (<147) U/l
Liver: y-GT = 20 ++ (<13) U/l
Pancreas: Fructosamine = 200 - (203-377) umol/l
Blood count: MCHC = 36 + (31-34) g/dl

6-25-2011 (urine test for Vetoryl dosage)

Cortisol-creatinine quotient 189.4 ++ (<33)

7-10-2011 (urine test for Vetoryl dosage)

Cortisol-creatinine quotient 170.5 ++ (<33)
Protein in urine = 24 -- (60-530) mg/l

11-11-2011 (urine test for Vetoryl dosage)

Cortisol-creatinine quotient 189.9 ++ (<33)

Thanks for any suggestions of what might still be causing Frito's excessive thirst/peeing/shaking/skittishness. And if this is Cushing's-related, given I have already tried high dosages of Vetoryl, I'm wondering what the treatment options are. Or if you can think of other causes. We are not sure how we should proceed.

S-

[Squirt's Mom]

Hi Steve,

Has DI been ruled out? Also, DM can come on remarkably fast so if he hasn't had his BG tested recently that might be worth looking into tho loss of appetite and weight loss is typical with DM.

Has he had an abdominal ultrasound?

What Cushing's treatments are available where you are? In some parts of the world, Lysodren (Mitotane) is not readily available leaving only Trilostane (Vetoryl) as the primary option.

I think if it were my baby, I would have a heart to heart with my vet and ask them to forget about Cushing's for right now and try to find another cause for the signs you are seeing and his abnormal lab values. Sometimes we all get tunnel vision once that term, Cushing's, has been put out there. ;)

I noticed that his amylase was extremely elevated in March of '09 - has he had any pancreas problems? any further elevations in amylase or lipase? Also, his T4 was low in May '11 - has hypothyroidism been ruled out?

Hugs,
Leslie and the gang

[scrisp]

Thanks much for the feedback.

Yes, he has not had an abdominal ultrasound, but was X-rayed during the diagnosis phase when he was very sick with what turned out to be ecoli. Nothing obvious that related to Cushings. My vet did note that it would take an ultrasound specialist to really tell (and I'm not sure what that would tell, and how reatment would vary depending on the results).

We discussed Lysodren (I think -- referred to as a derivative of DDD) and it was pointed out it was all they had prior to Vetoryl. It was an option, but he didn't seem to think it was likely to address Frito's current symptoms if Vetoryl didn't. He acknowledges he is not a specialist in this area -- indeed he offered to set up a meeting with a Professor in Zurich if that's what we wanted.

I did have that conversation with my vet (what else might be causing these symptoms).

I assume by DI you mean Diabetes Insipidus. Actually, our vet did mention that, but also indicated in over 30 years of practice, he had only seen one case and so indicated it was extremely rare (and thus unlikely). But in reading about DI, it certainly matches his drinking and peeing symptoms. But then, he also has shaking and nervousness, classic CS symptoms. Do you know if there is an easy way to diagnose and treat DI?

Frito had been tested for regular Diabetes (I guess DM), and that was ruled out.

Yes, Frito has had severe Pancreatitis on three occasions, which we now treat effectively with a rigid low-fat diet of prescription food.

And yes, we were wondering about his Thyroid, but our vet has ruled that out with blood tests.

For completeness, we will also note that Frito has had Lyme Disease, Leukopenia, and replacement of two cruciate ligaments.

As you can see, Frito is our "special" dog ;-)

Thanks for the suggestions, and we welcome other ideas.

If I didn't mention it before, we have decided to reduce Frito's Vetoryl dosage to 30 mg per day, and maintain that level for a month or so. We are now looking for other diagnosis and treatment for his thirst/peeing/shaking/nervousness symptoms.

S-

[scrisp]

As far as Frito's initial diagnosis, what symptoms led you to suspect Cushing's in the first place back last spring? I know you've spoken about skin/coat problems, but how about any other problems at that time? You noted in your earlier summary that it was around mid-October that Frito started drinking and peeing excessively. Was his thirst/urination normal prior to that? Other typical Cushing's symptoms are voracious appetite, excessive panting, seeking out cool places to lie, pot belly, lethargy, and loss of muscle mass leading to hind end weakness. Are any of these problems that you saw at the time of diagnosis, or subsequently?


Thanks Marianne. Yes, the initial symptoms were primarily extreme hair loss around his neck area, and some pot belly appearance. He also was quite lethargic back then. But thirst/urination were completely normal then.

And yes, he had been on 20 mg of Vetoryl with great results at getting his hair back - he looks like a young pup compared to an old dog -- really amazing. Then just before we went on a trip, he started to get up some during the night for water/peeing. We only noticed this in retrospect after it was a problem for our dog sitter, and Frito pee'd on their carpet -- something he had never done before. This continued after our return, and our vet had already recommended we increase his dosage to 30 mg based on a urine test just prior to our trip. So we started treating him for CS in April 2011, and first noticed excessive drinking/peeing in October 2011, and it has never subsided since.

So that means we have not had a solid nights sleep since then :-(

We are really looking for suggestions on what else could be causing this, and how we might be able to treat it.

Thanks for your time and thoughts,

S-

[SasAndYunah]

Hi Steve,

I saw on your blog that you are in Böblingen, and that's rather close to Stuttgart, right? I did a search for veterinary specialty clinics in Stuttgart and came up with the Dachswald Klinik (http://www.dachswald-klinik.de/index.php). The clinic is run by Dr. S. Reder, internal medicine specialist and if you ask me, that's what you need. A specialist to look at Frito, to run tests needed, etc. If there is no real diagnosis, you don't know what to treat and how to treat it. I'm not sure why your vet would sent you to Zurich if there's a good clinic nearby? And by your own vet's admission, he is no specialist. So my priority would be to go see a specialist...in the area :)

Saskia :)

[Squirt's Mom]

Hi Steve,

For Cushing's diagnostic purposes, an Xray is useless. An abdominal ultrasound done on a high resolution machine will show not only the organs involved in Cushing's - the adrenal glands - it will show the stomach, pancreas, kidneys, liver, intestines, bladder, gall bladder, spleen and other organs. As for the value of this test, let me share my Squirt's story with you.

Based on lab work for a dental, we started our Cushing's journey in early '08. Squirt had the LDDS, HDDS, ACTH, 2 ultrasounds and the UTK panel (full adrenal panel from the University of TN in Knoxville) and based on all five of these tests she was diagnosed with the pituitary form of Cushing's, PDH. However, after the second ultrasound I was told about a tumor on her spleen which had to come out immediately (the IMS who did the first one didn't find it important enough to make mention of even tho it was plainly visible :mad:). She had the tumor removed in Sept. of '08. After the tumor was removed, her cortisol returned to normal and has remained within normal range since - she does not have PDH in spite of five positive tests.

The stress from that tumor was causing her body to react just as it was supposed to - by releasing cortisol, among other things, in defense. Once the stressor was removed, her body realized there was no longer any need for the excess cortisol and production returned to normal. If I had not insisted on in depth testing and refused, absolutely refused, to rush into using either Lysodren or Trilostane, she would have died because she had been misdiagnosed even with extensive testing.

This is only one of the many reasons we tell new folks that Cushing's is one of, if not THE, most difficult disease to diagnose. But Cushing's also has a very good side in that it is an incredibly slowly progressing condition so we nearly always have time to make absolutely sure our baby does indeed have Cushing's, and not simply Cushing's-like signs and one positive test, before starting treatment with either of the two main drugs - Lysodren and Trilostane.

From where I sit, Frito has not been definitively diagnosed with Cushing's, he does not present like a cush pup, and, IMHO, the Trilo needs to be stopped immediately. I've been wrong once or twice before, or so they tell me :p, but I just don't believe a German or Dutch cush pup would present so differently from an American or Canadian cush pup. ;)

As for testing for DI - the water deprivation test is harsh but I'm not sure there is another/better option available - here anyway. I have heard of a dog who was diagnosed with DI by simply starting treatment - everything else had been ruled out and the DI treatment was successful, ergo the diagnosis of DI applied. Your vet is absolutely correct in saying DI is rare, it is quite rare, but that doesn't mean it isn't possible and Frito's signs seem to fit DI better than they do Cushing's...again, MHO.

Hugs,
Leslie and the gang

[scrisp]

Thanks to you both for the suggestions and the insights.

Here's the thing I can't seem to reconcile:

CS has a few distinct symptoms from what I understand:
- symmetrical hair loss
- pot-bellied appearance
- increased appetite
- increased thirst and peeing
- shaking
- skittishness

Frito has all of these symptoms currently, except it appears that the first two have been completely corrected by the Vetoryl, and appetite seems normal now as well.

So what condition would include such symptoms, and for which Vetoryl would fix that subset?

I feel like I'm on an episode of "House M.D.", and of course, I'm the dummy in the diagnostic group ;-)

I will look into the specialist in Stuttgart that was suggested. And will also consider the ultrasound (they probably go together).

Thanks again for the ideas.

S-

[labblab]

Steve, I strongly encourage you to schedule a visit with a specialist. Frito's history of symptom development just does not correspond to that of a typical Cushpup. I still think the original diagnosis is suspect if the only symptoms at that time were hair loss and possibly a pot belly. And hair loss limited to the neck is not typical of Cushing's, either -- the coat issues are more usually found on the back, flanks, and tail. As to why the trilostane might have initially helped with the hair loss even if Frito does not have Cushing's, take a look at this article excerpt by Dr. Audrey Cook (http://veterinarymedicine.dvm360.com/vetmed/article/articleDetail.jsp?id=491107&sk=&date=&pageID=5):


Treating alopecia-X

Alopecia-X is a dermatologic disorder usually described in Pomeranian, poodle, and husky breeds. It is related to an arrest in the normal hair growth cycle and has been associated with deregulation of both growth hormone and adrenal androgen synthesis.23 In classic cases, nonpruritic truncal alopecia occurs; no other signs or changes are noted.

Many of these dogs have elevated concentrations of the precursors to cortisol, particularly 17-hydroxyprogesterone. A recent study evaluating trilostane's effectiveness in 24 affected dogs (Pomeranians and miniature poodles) reported a 90% response rate within eight weeks.24 Trilostane was given once or twice daily, with a mean dose of 10.85 mg/kg/day. No adverse effects were noted, and it was concluded that the hair growth was related to downregulation of adrenal steroid synthesis or inhibition of estrogen receptors within the hair follicles themselves.24 Three affected Alaskan malamutes showed similar positive responses when given 3 mg/kg trilostane twice daily.25

It sounds as though "Alopecia X" is a coat condition that selectively afflicts only certain breeds, but it would seem that if trilostane is helpful with that coat condition, it may help with others as well. So I don't think that Frito's coat improvement is proof that the Cushing's diagnosis was correct. And the later development of the excessive thirst and urination, AFTER treating with trilostane, continues to raise many question marks. We do know that trilostane has the potential to increase certain intermediate adrenal hormones even as it lowers cortisol, so perhaps Frito has some complicated hormonal imbalance which the trilostane now is actually fueling and making worse. These are the kinds of questions that requires a specialist's insight and testing expertise. And I think the sooner Frito can be assessed, the better for you all. Depending upon what you mean by the "shaking and skittishness," these could be signals that his cortisol is too low instead of too high.

One more question for you: were Frito's urine samples "caught" by you at home and taken in to the vet, or were the samples obtained by the vet in-office?

Marianne

[scrisp]

Thanks Marianne for the additional info. It certainly is a complicated landscape out there.

To answer your question, we captured the pee, and made sure it was less than 3 hours old when it went to the vet. Usually more like an hour.

I will also note, FWIW, that when we dropped his dosage down to 30 mg, his thirst has seen a marked increase. Even before he was drinking too much (and we restrict it by manually filling up saucers) -- 4 cups at the highest dosage. While it is still very soon after the change, today looks like it will be 6 cups. That's a lot of water for a 10 lb dog!

Again, appreciate all of the suggestions.

S-

[labblab]

Steve, how is Frito doing? Any progress as far as getting a consultation with a specialist?

Marianne

[scrisp]

Hi All,

Frito is doing about the same, perhaps drinking more and getting up in the middle of the night more than before.

We've met with our Vet a couple of times, and we've decided to move forward with treatment with him, even though he is not a specialist. This was a conscious decision Carol and I made.

For anyone that disagrees with that approach, please just bear in mind that we are in Germany for another 18 months or so, and this makes it more challenging starting over with a new vet or finding the right specialist.

We are moving on to try Mitotane (Lysodren) at 25 mg/kg (so 125 mg) once per day for 5 days, and then will follow that with an ACHT test. This is a lower level dosage, and given Frito's recent Vetoryl (now stopped), our vet felt this was the safest approach.

We requested the change in medicine to see if it will have a positive clinical affect, specifically stopping his excessive thirst/peeing.

I know this approach may not be considered wise by some readers on this forum, but sometimes as pet owners one has to follow his instincts and advice from his trusted vet (who has managed to save Frito's life twice so far from unrelated issues). Please know that my wife or I am with Frito 24x7 and can keep a watchful eye for any negative changes in his behavior. We will keep hoping for clinically significant and improvement from the current situation.

We welcome any inputs from those that have either switched from Vetoryl to Lysodren, or just experiences with Lysodren in these lower than typical "loading" dosages.

Frito says hi, and hopes you all root for his improvement. He too wants his beauty sleep back ;-)

[labblab]

Steve, you are probably tired of hearing from me :o, but since you've asked for input I feel I must go ahead and make these comments. I do not have the time right now to provide citations (I will try to add them later on), but the general concensus among the experts is that, because of lingering effects on the adrenal glands, a "wash-out" period is imperative when switching between trilostane and Lysodren (either direction). The most conservative recommendation of which I'm aware is six weeks in between, without either medication. Others recommend a shorter time period. But I'm unaware of anyone who endorses an immediate switch, especially considering the fact that Frito has never had even one ACTH test performed. Thirst and urination notwithstanding, his cortisol level may ALREADY be at the target level that you would be seeking with Lysodren treatment. So starting off with Lysodren now at any dosage level, without any idea as to where Frito's pre-existing cortisol level is at, seems extremely dangerous to me.

If your vet has the capability of performing an ACTH test after five days, why has the testing never been done previously? Why is the testing not being done now, in order to assess the effect of the trilostane and prior to safely starting the Lysodren? This is the part I simply do not understand.

And are you sure your vet is truly talking about an ACTH stimulation test? I was a bit concerned when you told us your vet suggested you wait until a weekday to have the test performed, when you had time to "devote the day" to it. The ACTH only takes from 1-2 hours (depending upon the type of stimulating agent used). It is the diagnostic LDDS test (which Frito did have done) that takes 8 hours. But that test has no value as a monitoring test once treatment is underway. Your vet cannot use that test to determine the effectiveness or safety of either trilostane or Lysodren.

I am very worried about Frito's safety if you immediately proceed with this switch to Lysodren (even at a lower dosage) without the proper testing beforehand.

Marianne

[Squirt's Mom]

Hi Steve,

I am going to be a bit more blunt than Marianne - going from Trilostane (Vetoryl) to Lysodren (Mitotane), or vice versa, without a washout can be fatal to the dog. Not testing via an ACTH prior to starting Lysodren, ESPECIALLY without a washout, is extremely risky for Frito. This are simply facts regardless of where you live or what services are available to you.

If you cannot afford an ACTH right now, at least let Frito have a chance for a minimum of 30 days without either med in his system.

We all understand that you want Frito better as soon as possible and that he wants to feel better, too. However, we also doubt you mean to put his life at such high risk and so we speak out.

We will be here to support you and do our best to help Frito whether you trust our input or not - he and those like him are our only reason for being here and we fight to protect your baby just as strongly as we would our own when we see danger ahead. I hope you understand we are not disagreeing simply for the sake of argument or because we "know it all" - we speak from long experience and living with Cushing's on a daily basis...and because we care deeply for each baby that comes here.

Hugs,
Leslie and the gang

[labblab]

By the way, if your vet uses Cortrosyn as the stimulating agent for his ACTH tests, here's a very helpful tip that you can print off and give to your vet. This can save you a lot of money on multiple tests for a dog as small as Frito:

http://endocrinevet.blogspot.com/2011/03/how-to-extend-your-supply-of-cortrosyn.html

Here in the U.S., the cost of the testing is definitely expensive. So if that is also an issue for you in Germany, this tip can help make the testing much more affordable.

Marianne

[scrisp]

Hi Folks,

Sorry for my delayed reply -- I've been on business travel.

I acknowledge the risks that have been mentioned, and appreciate you keeping Frito's safety in the forefront. And I realize you are writing both for me and others that might read these posts with similar situations.

We think we understood the risks, as well as the consequences of not finding suitable treatment, and so proceeded with our eyes wide opened, in part due to your well-informed cautions.

So here is where we stand. Frito has received 125mg Lysodren once per day for 5 days. There have been no negative side affects. And many positive side affects: his shaking and nervousness has significantly been reduced; has thirst is much reduced -- down to about 3 cups of water per day compared to 6 cups of water per day after we took him off the high dose of Vetoryl (though should be about 2 cups for his weight); he acts spunky with lots of energy; and his appetite is strong.

Today we took him in for his ACHT test. He's had his initial blood drawn and the stimulant administered (boy, he didn't like that shot ;-). He is fasting still and not real happy about that. My wife will take him back in 4 hours for the second blood draw.

We intend to continue the low dose loading for two more days until we get the results of the ACHT test, since he his handling it so well, and he still needs further symptom control (additional thirst reduction).

In any case, we are very excited to see some forward progress toward getting his symptoms under control. Will post the test results once we get them. I finally see some hopeful light at the end of the tunnel.

Thanks again for all of your inputs and insights -- cautionary or otherwise. We appreciate your time, experiences, and expertise.

S-

[labblab]

Dear Steve,

Thank you so much for coming back to update us. I am delighted that Frito is tolerating the Lysodren well and that you are already seeing improvements!

However, I do have one more "But..." to bring to your attention :o. I am sorry to have to do so, because I'm so afraid you'll one day quit posting out of frustration with all our warnings :(. But once again, this feels very important to me to mention. I am worried about the "ACTH testing":


Today we took him in for his ACHT test. He's had his initial blood drawn and the stimulant administered (boy, he didn't like that shot ;-). He is fasting still and not real happy about that. My wife will take him back in 4 hours for the second blood draw.

With an ACTH test, there should only be 1-2 hours between the two blood draws -- not 4 hours. It is the LDDS test that requires blood samples at 4 and 8 hour increments after the initial draw/injection. And unfortunately, the LDDS has no value in monitoring the effects of either trilostane or Lysodren. Please read this description of the ACTH test:

http://endocrinevet.blogspot.com/2011/03/whats-best-protocol-for-acth.html

Per the last paragraph of the article, your vet may be using Synacthen as the stimulating agent instead of Cortrosyn. But as you will see, with either agent the testing should take only one hour to complete. There is also a "gel" stimulating agent that is sometimes used, and with that, the testing window shifts to two hours. But your vet's time frame of four hours has me really scratching my head.

Please do confirm that it is REALLY an ACTH stimulation test that is being conducted, and not another LDDS test (which was the test by which Frito was originally diagnosed).

Marianne

[Squirt's Mom]

Hi Steve,

Ya know, sometimes no matter how hard we try, folks just follow their own protocols and hope for the best. Sometimes they work, sometimes the dog pays dearly. But, either way, we can do no more than share how this works and hope folks listen - then sit back, watch, pray, and offer support.

I will say one more thing about the testing in addition to what Marianne has so kindly explained - Lysodren continues to work for 48 hours after the last dose so having an ACTH done the same day, within hours of a dose isn't going to tell you what you want to know either. The ACTH should be done 36-48 hours after the last Lyso dose was given because the cortisol will continue to fall during that 36-48 hour window. Getting a "good" reading a few hours after a dose, then continuing to load is dangerous.

A link on Lysodren loading and tips -

http://www.k9cushings.com/forum/showthread.php?t=181

I am glad to hear he is doing well so far and sincerely hope that trend continues. And please, please, keep in touch as I and others are quite concerned.

Hugs,
Leslie and the gang

[scrisp]

Hi Folks,

Sorry I've been away for a while. I wanted to find out how things were working before reporting back. Bottom line: the news is Good!

So we had the ACTH test and got the results back, only to confirm what we heard from some of you -- the test was not correctly administered, so we don't think the results are meaningful; disappointing given how much it hurt Frito to get the stimulation shot, and its cost.

So we just decided to continue the Lysodren, and even increase its dosage, and watch carefully for the loading symptoms. We increased dosage to 125mg x3/day and after only 2 or 3 days at that level, the affects were clear -- loss of appetite and lethargy; though somewhat surprisingly, not really loss of thirst.

So we stopped the Lysoden at that point (that was 6 days ago, last Sunday), and have been monitoring Frito since. We also put back out his water dishes, and are letting him drink as much water as he wants/needs. He is sleeping much more now, but frankly no more than he did before Cushings was in full swing and keeping him hyped up. He is now able to sleep through the night, or gets up at most once to pee. His appetite remains low until around noon, and then he seems to be eating normally (much less than under Cushings). He is very relaxed and calm, and seems quite happy. In short, he is acting like a pretty normal elderly dog.

Our thought is to hold off on the maintenance dose of Lysodren until his morning appetite coms back. We are happy that Lysodren has had a positive affect on his Cushings symptoms, whereas the Vetoryl did not (except for reversing his hair loss). He looks fantastic.

So that's the latest. I welcome your inputs on when to start the Lysodren maintenance dosage, and what level that should be. My current guess is 125 mg x2 for 2 days/week.

I know this "seat of your pants" approach is not something many on this forum would recommend, but it is working for us, and we plan to continue it (no disrespect intended). Sometimes, I think, since we know Frito's behavior so well, we can watch for changes and adjust accordingly, so long as we are working with the right medicine. And it certainly appears that the Lysodren is having the desired affect.

Wishing you all well, as I sit outside on this beautiful Spring day in Germany, with Frito at my feet soaking up the sunlight and sniffing out the warm breeze.

All the best,

S-