Please advise-Stroke-Cushing's-Adrenal tumors

[marinaliz]

Hi everyone! My beloved 14.5-year old dog Liza has recently diagnosed with Cushing’s. I can not believe that 40 days ago she was jumping, running, climbing stairs, playing with our one-year old son, and now she seems in quite bad condition. Our life has been changed so quickly. To take things from the beginning though…

Below I post her lab tests going back almost 3 years ago. I'll post any that were off with the appropriate ranges.

May 2012:
ALP 130 (18-110)

November 2012:
ALP 185 (18-110)

June 2014:
ALP 616 (0-90)

July 2014:
ALP 822 (18-110)

July 2014:
LDDT:
Cortisol (1st sample) 4.01 (0.7 – 9 μg/dl)
Cortisol (2nd sample) - 4 hours 0.35
Cortisol (3rd sample) - 8 hours 0.43
Vet said no cushing’s

January 2015:
ALP 748 (18-110)
Triglycerides: 932 (2-242)
Cholesterol: 332 (148-329)

May 2015:
ALP 1190 (23-212)

June 2015:
ALP 1213 (18-110)
Triglycerides: 692 (2-242)

June 2015:
LDDT:
Cortisol (1st sample) 5.3 (0.7 – 9 μg/dl)
Cortisol (2nd sample) - 4 hours 0.96
Cortisol (3rd sample) - 8 hours 0.8
Vet said no cushing’s

Unfortunately, in October 2015, Liza had had a severe stroke. She was totally paralyzed from the left side of her body! After 7 days from the stroke we performed an MRI to the brain which indicated an ischemic stroke and damage to the cerebellum. The good news is that now (after about one month) she seems quite better but still has few problems with her balance (especially in the morning). She can even run sometimes, eat by herself etc. The bad news is that during the first days (6-7 days) after the stroke we were giving her prezolon (to address potential hemorrhagic stroke which was eventually not confirmed by the MRI) and I believe that we accelerated cushing’s. In fact, few days after the stroke, she started urinating everywhere in the house (5-6 times per day) and drinking much of water (0.5-0.6lt/24 hours).

The day we performed the MRI to the brain we also performed abdominal ultrasound, and two masses (24mm and 6mm) on the left adrenal gland were found (benign nodules functional or non-functional / benign neoplasm / malignant). Liver appeared with increased dimensions and normal echogenicity. No metastases to other organs were found. We also performed the following blood tests:

November 2015:
ALP 1400 (18-110)
Triglycerides: almost within normal range
Cholesterol: within normal range
AST, ALT almost within normal range
LDDT:
Cortisol (1st sample) 151 (20 – 250 nmol/L)
Cortisol (2nd sample) - 4 hours 40.3
Cortisol (3rd sample) - 8 hours 58.7
This time the above samples were sent abroad (I think in U.K.)

I was told by the vet that adrenal dependent Cushing's disease was eventually confirmed (in literature it is written that dogs with cushing’s is at an increased risk for a stroke). He also suggested treating symptoms medically with Vetoryl and that surgical removal of the adrenal gland is absolutely not recommended in case of my dog mainly due to her age. I also met some other doctors who told me the same. As far as I can understand, adrenal dependent Cushing's is a rare disease in dogs, but I feel incredibly guilty to do nothing! They all say to me that the possibility of metastasis is quite small at her age. Besides they believe that the elevated ALP levels indicate that the masses do exist for almost 2 years ago. I am wondering if there is anyone else who didn’t proceed to surgical removal and share this experience with me. I am very depressed and I don’t know what to do. Unfortunately, in the city I live (Athens, Greece) I can’t find a specialist doctor for this serious disease and I am very afraid of my dog’s life. I am not prepared to lose her yet. At least I want to know that I am doing the best for her.

I should mention that the day before yesterday, I started treatment with Vetoryl. The starting dose is 30mg once daily. Then we will give her 60mg once daily. Μy dog weighs 12 kg. After ten days the vet will perform again blood tests. Is it normal that I am not seeing any improvement yet? She still urinates more than normal.

Thank you all so much. Hoping that still there is a small bright side of the situation and the end has not come yet.

[labblab]

Hello and welcome to you and your sweet Liza. We are really glad you've found us!

I am very sorry to hear about your girls's stroke, but it is indeed good news that she seems to have recovered a fair amount of function. Hopefully she may progress even more over time.

Given her somewhat confusing blood test results, I am really glad you've also had this imaging done. There do seem to be significant differences between the lab results performed at home vs. the ones that were sent out for analysis in November. And even though this final LDDS test is finally "positive" for Cushing's, the pattern of results is actually consistent with the pituitary form of the disease. However, since Liza had an MRI of her head, I'm assuming there was no pituitary tumor to be seen. So that leaves us all suspecting that the adrenal nodules are the culprit. And Cushing's does seem to be linked to an increased vulnerability to blood clots, such as would be the case with Liza's ischemic stroke.

I do understand why the vets are expressing reservations about surgery for Liza, given her age and also the surgical risk for creating yet another clot. When surgery is not a good option, Vetoryl is indeed commonly prescribed for treatment of adrenal Cushing's and it can be used successfully to lower cortisol levels. So up to this point, I take no issue with your vet's recommendation. My one concern is with the dosing progression they are recommending. Regardless of the type of Cushing's, the revised dosing recommendation is to approximate a formula of 2.2 mg. per kg. (or 1 mg. per pound) for the first thirty days of treament. So Liza's dose should not exceed that 30 mg. capsule (the exact formula for her would be 2.2 x 12 kg. = 26.4 mg.). Here's a link to the newest treatment and monitoring guidelines published by Dechra, manufacturer of Vetoryl. Pay special attention to the flowchart.

http://www.dechra-us.com/Files/dechraUSA/downloads/Client%20Literature/Treatment%20and%20Monitoring%20of%20Hyperadrenocor ticism.pdf

It is good that your vets plan to retest after ten days on the Vetoryl. But this time, the testing needs to include an ACTH stimulation test. And again, unless Liza's cortisol is found to be dropping too low, the dose should remain unchanged for the first thirty days of treatment. It can take a little while to see symptom improvement, so please don't be discouraged that you have not seen immediate results. And please do keep us updated!

Marianne

[marinaliz]

Hello again! I am grateful for your immediate response. I really appreciate your advice. You can not imagine what we have going through during the last 30 days. Before the stroke, no one could imagine the age of Liza. All people assumed that she was a maximum of 8 years old. Just after the stroke, we all believed that a brain tumor was the culprit. Right after the MRI, I felt for a few minutes a relief and I was crying for joy, but after the results of the ultrasound I realized that again we get into adventures that are going to last for a long time before starting to clear up the situation.

- I am little confused… I have already given her 3 times the 30mg dose (once daily), the vets reassured me that it is a small dose… Shall I continue with this dose (for 30 days) or shall I decrease it? Thank you very much for the guidelines you sent to me. They suggest 2.2mg/kg as starting dose. So the 30mg isn’t such high or is it?

- Furthermore, you wrote that the results are “barely positive” and the pattern is actually consistent with the pituitary form of the disease. What makes you believe this? Vets haven’t mentioned anything like this and I am really afraid because they aren’t highly experienced with Cushing's. I should mention that the LDDT was performed after approx. 10 days we stopped prezolon. Do you believe that a false positive result may have been caused due to prezolon? Furthermore, if a false positive result is the case, so what we have here? Atypical cushing’s? Please note that according to MRI results there is no pituitary tumor in her head.

- Unfortunately, I am not so sure about the ACTH simulation test. I know that it is required but vets told me that during this time period the test is not available in our city. I don’t know what they are going to check in 10 days, really. I will call my vet and ask him to order from abroad whatever is necessary for making the retest after 10 days on the Vetoryl.

- One last question…. Have you seen/hear dogs with adrenal dependent Cushing's to survive for some time without metastasis? Is it somewhat good that up to now there is no metastasis and probably these two masses (24mm and 6mm) do exist for at least two years (based on the high ALP levels recorded)? It is very important for me to get an answer for this.

Once again thank you so much for your time and advice. I can not believe I' m talking to someone who has so much experience with this disease. Please keep going like this. I wish you all the best from the bottom of my heart.

[marinaliz]

I forgot to mention that during the last year Liza is on diet and eats specific foods that mainly protect liver function. Perhaps this is the reason of Triglycerides reduction over time.

[spdd]

I cannot give you any advice as I am not experienced enough, but to give you encouragement, if it wasn't for the knowledge on this forum,I would have lost my dog I'm sure 2 years before it was his time. They know their stuff on here, and if it wasn't for them well...., the vet actually gave me very poor advice which almost resulted in his death.
The people on here are experts, and with their guidance I got more time with my beloved boy. Just thought I'd let you know.

[marinaliz]

Spdd thanks for your reply and encouragement and I am really sorry for your dog. I know that my little girl is now an elderly dog but all have come so suddenly and I can’t accept to leave her to her fate. She is my little girl for 14.5 years, I have her next to me all these years. I want the best for her. And most importantly not to suffer.

[labblab]

Hello again! I am happy to try my best to answer your questions. AS you'll see, I've taken your questions one-by-one, and then added my answers in red.

Your questions:

- I am little confused… I have already given her 3 times the 30mg dose (once daily), the vets reassured me that it is a small dose… Shall I continue with this dose (for 30 days) or shall I decrease it? Thank you very much for the guidelines you sent to me. They suggest 2.2mg/kg as starting dose. So the 30mg isn’t such high or is it?

I think the 30 mg. daily starting dose is fine to continue as long as Liza does not start exhibiting any ill effects such as vomiting, diarrhea, or marked lethargy. Based on the most current recommendations of Vetoryl's manufacturer, however, I would not want to increase the dose any further until at least thirty days have passed. Here's a link to a reply on our Resources forum that explains why I would not want to increase the dose before the first month has passed:

http://www.k9cushings.com/forum/showthread.php?p=1251#post1251

- Furthermore, you wrote that the results are “barely positive” and the pattern is actually consistent with the pituitary form of the disease. What makes you believe this? Vets haven’t mentioned anything like this and I am really afraid because they aren’t highly experienced with Cushing's. I should mention that the LDDT was performed after approx. 10 days we stopped prezolon. Do you believe that a false positive result may have been caused due to prezolon? Furthermore, if a false positive result is the case, so what we have here? Atypical cushing’s? Please note that according to MRI results there is no pituitary tumor in her head.

I thoroughly apologize because I miscalculated when I said her result on the test was barely positive. I was converting your European units into the units we commonly use in the U.S., and I'm afraid I made a mistake with my math the first time around :o. In order to convert from nmol/L (your units) to ug/dL (U.S. units), we take your units and divide by 27.59. If we do that, Liza's 8-hour result was 2.1 ug/dL (58.7 nmol/L divided by 27.59 equals 2.1 ug/dL). You did not give us the "normal" reference range for that 8-hour value, but typically a dog without Cushing's will test below either 1.4 or 1.5 ug/dL at the 8-hour point. If that was the normal range for Liza's test, then yes, 2.1 ug/dL is indeed positive for Cushing's.

However, both her 4-hour and 8-hour results were less than 50% of her baseline level. That pattern is consistent with the pituitary form of Cushing's. Since the MRI did not reveal a pituitary tumor, however, we have to assume that result is somehow an oddity of her test. Here is a link that explains the interpretation of LDDS tests in greater detail:

http://veterinarymedicine.dvm360.com/clinquiz-interpreting-low-dose-dexamethasone-suppression-test-results

As far as the prezolon, I cannot give you a definite answer about it, but if it had been stopped as long as ten days before the test, I would doubt that it affected the results.

- Unfortunately, I am not so sure about the ACTH simulation test. I know that it is required but vets told me that during this time period the test is not available in our city. I don’t know what they are going to check in 10 days, really. I will call my vet and ask him to order from abroad whatever is necessary for making the retest after 10 days on the Vetoryl.

We do understand that the substance that is required to perform the ACTH stimulation test may be in short supply in Europe. If your vets can obtain the substance from elsewhere, that would be great. If not, they may have to rely on a baseline cortisol level along with a retest of Liza's basic blood chemistries. This is primarily to make sure her cortisol is not dropping too low, however. As long as she is behaving normally and those basic tests are within normal range, hopefully you are safe to continue with that 30 mg. dose until the end of the thirty days. At that point, her symptom resolution will more strongly factor into the decision re: a possible dosing increase. But we can talk about that more later.

- One last question…. Have you seen/hear dogs with adrenal dependent Cushing's to survive for some time without metastasis? Is it somewhat good that up to now there is no metastasis and probably these two masses (24mm and 6mm) do exist for at least two years (based on the high ALP levels recorded)? It is very important for me to get an answer for this.

Yes, we have had members here whose dogs have survived for a lengthy period of time with adrenal Cushing's without metastasis. So it is definitely possible. :)

[molly muffin]

Hello and welcome. My molly has a nodule that hasn't metasized and that they think isn't secreting because it hasn't grown in the past year, but I imagine it is anyones guess without surgery to know for sure.
She is doing fine. A few other problems that give us headaches some days, but over all she is okay. So I think that if she recovers from the stroke well and she doesn't go too low, then she should be okay on the 30mg dose. I wouldn't raise it to 60mg though. That seems to just be asking for trouble.
See how she does, stop the medication at once if she exhibits any of the symptoms Marianne mentioned (voimiting, dirrahea, excessive lethargy, refusing to eat or drink).
I am guessing they will do a baseline and electrolyte tests. That is what I'd want if they can't get the stimulating agent.
Probably want to have them do regular checks of her blood pressure too as hypertension can go along with high cortisol.

[marinaliz]

Once again I would like to thank you all for your interest and the detailed advice you provide.

Liza today took her 4rth Vetoryl pill. I think that she looks a bit weaker and calmer, I’m not sure if it is due to the pill or due to the stroke. In fact, before taking Vetoryl I think that she was a bit more “lively”. Except this weakness, I don’t see anything else strange (at least at the moment). Is this weakness a “normal” side effect of Vetoryl? I have my eyes on her in order to notice if something (vomiting, diarrhoea, etc.) goes wrong. However, she still eats with appetite and begs for food.

As far as the water intake is concerned, she still drinks the same amount as she drank before Vetoryl (0.5-0.6 lt/24hours which is not considered such high). It hasn’t changed at all. In fact, she drinks exactly the same amount of water for almost two years ago where I am monitoring her very closely. The strange thing is that before prezolon she urinated 2 times per 24 hours. After prezolon she started urinating more than 5 times per day while she kept drinking exactly the same amount of water. This is quite strange.

[marinaliz]

Hello again,

Today Liza took the 7th pill of Vetoryl. All these days she didn’t display any of the bad side effects (vomiting, diarrhea, etc.) of the drug. The only change I have noticed is that her appetite has become more selective. This is the reason that yesterday and today I changed her diet. I also have noticed that since yesterday she is drinking too much of water.

In the past three hours she made one (very small) diarrhea. Since yesterday evening urinates excessively. I called my vet who told me not to worry. He said that the diarrhea maybe is due to the change in her food and Addison’s is unlikely as she takes the lowest dosage (30mg once daily) of Vetoryl. As far as the excessive urination is concerned, he told me that maybe Liza has a urinary infection, which is very likely because, after the stroke, sometimes she losses her balance when she urinates and falls down… The vet suggested me to collect a urine sample the next hours, put it to the fridge and on Monday (now we have Saturday evening) to send it for further microbiological analysis. At the same time, the vet suggested start giving (today or tomorrow) to Liza “Baytril” tablets (enrofloxacin) to cure the possible urinary infection. Can you please advise me if there is any contraindication in administering at the same time Vetoryl and Baytril?

Thanking you in advance.

[Harley PoMMom]

I know of no contraindication between Vetoryl and Baytril. I want to make you aware that a dog can have an addison's crisis on any dose of Vetoryl. Dechra, the makers of Vetoryl, state this is their product insert:
WARNINGS:
Hypoadrenocorticism can develop at any dose of VETORYL Capsules. In some cases, it may take months for adrenal function to return and some dogs never regain adequate adrenal function.

This excerpt is also noted:
Owners should be instructed to stop therapy and contact their veterinarian immediately in the event of adverse reactions such as vomiting, diarrhea, lethargy, poor/reduced appetite, weakness, collapse or any other unusual developments. If these clinical signs are observed, conduct an ACTH stimulation test and serum biochemical tests (with particular attention to electrolytes, and renal and hepatic function).

This information and more can be found here: http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf

Keep us updated.

Hugs, Lori

[marinaliz]

Thanks for your reply. Unfortunately, Liza had few more diarrheas (3) during the night. I am afraid that it is not due to the change in her diet and maybe it is due to the drug. I am going to take her to the hospital immediately and I stop Vetoryl, at least for today. Do you agree? Could you please advise me what steps should I follow? What type of blood tests should we run? Is there anything else we should do? As I have already told you vets here, although they seem really interested about Liza, they are not highly experienced with Cushing’s.

I am so disappointed and confused. Liza seemed to go well with her treatment although I hadn’t any notice improvement in Cushing’s signs (urination and water intake). From yesterday, she has diarrheas. Furthermore, she has increased urination and increased water intake (quite more than previous days).

[marinaliz]

We are now back from hospital. Vets assured me that her symptoms are not related to Addison’s and diarrheas have been caused from the change I made in her food. They performed blood tests including potassium, sodium, baseline cortisol, ALP, other liver enzymes etc. I will know most of the results tomorrow. They gave her serum and some anti-diarrheal medication. They found her condition quite good and definitely not life-threatening and also suggested me not to stop Vetoryl. She has appetite and asks for food. I will feed her some homemade dietary food. Furthermore, first results from urine analysis didn’t show an infection but we are going to retest it tomorrow with a morning urine sample.

Hoping that the increase I have noticed (from yesterday) in urination and water intake is not due to a sudden a worsening of her disease…especially now that we have started treatment with Vetoryl.

[Squirt's Mom]

I am glad you took her on in...you can rest a bit easier in your heart with this til it is cleared up. NOW you know why we say to never change the diet when starting treatment - the reaction to a food change can be the same as reaction to an overdose. ;) You will be a voice of experience and reason on this aspect from now on! :D

[labblab]

I am so glad you took Liza in to be tested. In honesty, though, until they have the results back from the blood tests, your vets cannot know whether or not the Vetoryl is contributing to the problem. It is very good that, outwardly, she does not look to be ill. But until the test results are back, you cannot know what is going on inwardly.

I do worry that she had become so picky about eating that you have had to change her food. This could be a sign that her cortisol is actually dropping too low.

I know your vets keep insisting that she is on a low dose, but every dog reacts to the drug differently. So a dose that is correct for one dog may end up being too high for for another dog of the exact same weight. Vetoryl also comes in 10 mg. capsules, and manufacture has also begun on 5 mg. capsules. So as you can see, there are smaller dosing options available other than the 30 mg. you are currently giving her.

Also, you had asked about the Baytril. I am not aware of a problem giving the drugs together, but antibiotics can cause GI upset such as nausea or vomiting in any dog. So without confirmation of the presence of active infection, it seems to me as though you may be running the risk of confusing the picture even more by giving an antibiotic right now unless there is reason to do so. I know it is hard to confirm the presence of infection, though, when urine is highly dilute. So the possibility of a UTI is indeed a dilemma.

If a UTI is not involved, it's hard to explain the increasing thirst and urination. I think it will be important to see how Liza's kidney and liver values look on yesterday's bloodwork.

And if she should worsen in any way before those tests are back, I still would hold off on giving her more Vetoryl. As I say, at this point, there is really no way to know whether it is causing a problem or not.

Marianne

[Harley PoMMom]

Furthermore, first results from urine analysis didn’t show an infection but we are going to retest it tomorrow with a morning urine sample.



When a dog has diluted urine a regular urinalysis may not pick up the bacteria in the urine, therefore, an urine culture and sensitivity test is recommended as this can show exactly what bacteria is growing and then the appropriate antibiotic can be prescribed.

Hugs, Lori

[marinaliz]

Thanks to all of you for your advice. Unfortunately Marianne is right. I haven’t got the blood-test results yet. Yesterday Liza seemed quite ok and her diarrheas stopped (for 24 hours) after we were back from hospital. Unfortunately she just had another diarrhea. Otherwise, she looks quite fine, at least for the moment. She also has appetite and asks for food. I am trying to contact my vet to ask him to speed up the results but I can’t find him. I should mention that I haven’t stop Vetoryl, since yesterday, vets in the hospital assured me that the drug was not the case. Diarrheas are always considered a first sign of Addison’s or this dosage may be too much for her and causes her a mild gastrointestinal disorder?

As soon as I get the results, I will be back with an update. Many thanks to all of you….

[marinaliz]

I'm sorry for asking so many questions but I have been so panicked. I am afraid that vets maybe missing something. Liza just had another (second) diarrhea.

-Can you please advise me if I get the results and Liza’s cortisol level has dropped too low what emergency action steps should we follow?

- I want to give her again anti-diarrheal medication to stop diarrheas. Is it contraindicated?

[labblab]

You never need to apologize for asking questions! That's what we're here for. :)

If Liza's cortisol were to drop too low, you would stop the Vetoryl entirely and depending on the severity of her abnormal behavior, you would also give her some supplemental steroid (like prednizone or prezolone) in order to make up for the natural cortisol she is lacking. The typical "rescue" dose of prednisone is 0.25 mg. per kg.; I am not sure how the dosage for prezolone corresponds to prednisone.

If Liza's electrolytes were also abnormal, then she could also need a supplemental substitute for aldosterone, another adrenal hormone.

Please be aware that I am not a vet, so it is not my place to advise you to do anything contrary to your own vet's instructions. But if Liza were my own dog and she was continuing to have diarrhea, I would tell my vet that I wanted to stop the Vetoryl entirely until those blood tests results are available. Missing a couple days of Vetoryl really won't make much difference to her health since you can always start right back up again once you know her tests are OK, but continuing to give the Vetoryl if her cortisol has dropped too low can risk making her much sicker. So that's what I'd do if she were mine.

What anti-diarrhea medicine are you giving her?

Marianne

[marinaliz]

Yesterday I gave her Diarsanyl Plus (oral paste) and I don't know what was the injection they made in the hospital. I am home and I am waiting the vet to call me and inform me the results. Now it is 7.00PM. He told me that he will probably know her results by 8.00PM or tomorrow morning.

Now she is sleeping and I think she is also weak. She hadn't do another diarrhea.

[labblab]

Nutritional Supplement for maintaining digestive function and coating intestinal mucosa. Nutritional constituents: montmorrillonite, electrolytes (sodium chloride, potassium sorbate, magnesium citrate), sugars (fructooligosaccharides, dextrose, glycerol).

I just looked up a description for Diarsanyl Plus, and here is what I found. Normally, it should probably be fine to use. My only worry is that if Liza were actually to be suffering from an overdose of Vetoryl, her sodium level might be low and her potassium level too high. So giving her supplemental sodium might be helpful, but giving her even more potassium might not be good. I truly am just guessing here, but as long as she hasn't had any more diarrhea, I probably would not give her any more of this paste, either, until you know for certain that her balance of sodium and potassium is OK.

I don't like hearing that she is weak. :(

If she were to get worse during the night, is there an emergency vet that you could take her to see?

[marinaliz]

The hospital is about 1hour away from my home by car. Nevertheless, I have just informed that I will learn the results within one hour by now. I called my vet (his clinic is 5 min from my home) and I will get Liza to him at 8.00PM. I am really very afraid. I know that the results will be bad.

[labblab]

OK, now take some deep breaths! I totally understand how scared and worried you are. But the news may not be all that bad at all. Her body may just be reacting to the lowering of her cortisol, but without any truly dangerous lab readings. Or, your vets may be totally right, and her diarrhea may not be related to the Vetoryl at all. So everything may actually be alright once she gets over this GI upset.

Definitely let us know what you find out!!

[marinaliz]

And obviously I am going to stop Vetoryl. She seems that she cannot afford the 30 mg dosage, although it is the smallest dosage for her weight.

On the other hand, I am so afraid to discontinue Vetoryl because this could accelerate her Cushing's. And most importantly, if Cushing's is the culprit for the stroke, it may occur again.

Maybe should we try a lower dosage, as you suggested (10mg for example). Am I right? Please tell me yes...... I am so sad...

[labblab]

Yes, definitely, you can end up trying a smaller dose if the 30 mg. is too much for her. You can combine smaller capsules (5 mg. and/or 10 mg. capsules) in order to come up with the dose that is best for her. We have had many dogs here who needed to drop back to doses that were less than 1 mg. per pound (2.2 mg. per kg.), but then did very well and saw their Cushing's well-controlled on those smaller doses.

So by all means, try not to feel too down-hearted. It is not uncommon at all for dogs to end up needing to have their doses adjusted.

Marianne

[molly muffin]

Have you heard anything back from the vet yet about the test results.

I do know that a gastro upset can happen for any number of reasons and not be associated with low cortisol from the durg, although you do want to check if that is the case always.

My dog had a gastro upset that lasted with diarrhea for gosh, a few weeks and it finally got better with the antibiotics for stomach and some plain pumpkin. As you I had the blood tests to make sure she hadn't gone too low and the results came back fine, but the diarrhea persisted, so don't be to disheartened till you know the results and what the next possible step will be.
I also added in the probiotic florafora to her diet, some in the morning and some at night, a bit of plain pumpkin and I did chicken and rice for awhile too. During that time I stopped the vetroyl till she was a bit more on the normal side.

Do let us know what the tests show!

[marinaliz]

Finally we came back home from the vet. Before posting the results, I would like to express my gratitude for your advice and for your interest. Thank you all so much!!!

Νο Addison’s!!!!! Diarrheas have been caused from the change I made in her diet.

Ι should mention that the blood sample was taken yesterday (after 7 days we have started treatment with Vetoryl). Furthermore, the sample was taken in the morning before Liza taking her daily dose.

I'll post only the results that were off with the appropriate ranges.

ALT 121 (25-93 IU/L)
ALP 669 (18-110 IU/L) (The day before staring Vetoryl this value was 1400)

The three values below, although may seem very high, my vet told me Ι should not worry and that they attributed to the diarrheas and dehydration. Furthermore, the protein to creatinine ratio (Urine protein / urine creatinine) is within reference values, i.e. Liza has 0.13 and the normal range is <0.5.

Creatinine 2.9 (0.8-1.6 mg/dl)
Urea nitrogen (BUN) 79 (9-24 mg/dl)
Urea 174 (19-53 mg/dl)

Other exams such as potassium, sodium, baseline cortisol are all within reference values.

We have also ordered from abroad the ACTH simulation test and the next few days we will perform it.

Finally, as I have already mentioned, results from regular urine analysis didn’t show an infection but I am going to wait two more days to get the results from the urine culture. However, water intake seems that has been slightly reduced.

[molly muffin]

This is good news :) So either the diet or she as a stomach bug (not unusual for a dog)

Hoping for continued improvments

[labblab]

So glad to hear that Addison's doesn't seem to be part of the problem! I'm also really glad you'll be able to perform the ACTH testing. In that vein, here's a couple of thoughts going forward.

First, on the morning of the ACTH test, make sure that Liza takes her Vetoryl along with breakfast. In order to be metabolized properly, the drug needs to be given along with a meal. Otherwise, you risk a testing result that is higher than it would be on every other day. Since this last baseline cortisol was tested before Liza had her Vetoryl at all that day, we can guess that even her baseline cortisol may be running lower at other times of the day when the Vetoryl is most active in her body.

Also, the ACTH testing needs to be performed 4-6 hours after the Vetoryl is given with breakfast. Again, this is to make sure that you are measuring the effect of the Vetoryl at the time it is driving the cortisol to its lowest point within each daily cycle. Both for safety's sake and also in order to make proper dosing decisions, you want to know what the cortisol level is at its lowest point.

Last but not least, I would want to have Liza's kidney values retested again when she is not dehydrated, perhaps when she is having blood drawn anyway for the ACTH. It is true that dehydration can affect various lab values, including kidney markers. But I would want to make sure those kidney values have truly normalized again, and especially if Liza's thirst/urination show no real improvement. Probably there is nothing to worry about re: her kidney function, but it will be nice to see those values -- especially the creatinine -- closer to normal again.

Overall, how is our girl doing today?

Marianne

[marinaliz]

Hello! I will certainly follow your instructions regarding the ACTH test. Many thanks again!!

Today is the tenth day on Vetoryl. My vet suggested performing the ACTH test after Monday, which will be the 16th on Vetoryl, as we have now these recent blood test results. During that day we will certainly recheck creatinine levels. Do you think that it is a big time interval? Today we have Tuesday.

Furthermore, the vet relied mostly on the urine protein to creatinine ratio which is very good for Liza and he said that it is an indicator of normal kidney function. Please tell me if you don't agree with this. Is it possible to have abnormal kidney function and this ratio to be normal? He was not worried at all about the level of creatinine, which has been caused, as he said, from the dehydration. However, I am afraid the case that Vetoryl damages her kidneys’ function, especially if it is combined with the increased thirst/urination thing which has not been significantly reduced.

Diarrheas have been stopped since yesterday but still she seems a bit weak. Τhe kinetic recovery from the stroke seems that has been stagnated during the last days with these diarrheas episodes.

[labblab]

As long as Liza doesn't worsen in the meantime, waiting until Monday to retest should be fine. And your vet is probably absolutely right that the kidney elevations were due to dehydration. I just tend to be a worrier, though, so I like to see abnormal values returning to normal. :o

The fact that Liza's urine protein to creatinine ratio was normal is indeed a very good thing. Most serious kidney diseases cause damage that abnormally allows protein to pass into the urine from the bloodstream. So the fact that there was no protein in Liza's urine is a good thing. However, there are some kidney problems that don't involve protein loss.


Proteinuria does not always accompany renal disease. Pyelonephritis [infection in the kidney], urinary tract obstructions, kidney stones (nephrolithiasis), tumors, and congenital malformations can cause severe illness without producing proteinuria.

Elevations in blood creatinine and BUN signal a different type of filtering problem than does the urine UPC test. Elevated blood creatinine and BUN result when the kidneys are not properly filtering toxins out of the bloostream. They do not test protein loss. So if Liza's blood markers remain high even when she is not dehydrated, I would want to know whether there was something else going on with her kidneys that was causing the abnormality.

But I am undoubtedly worrying you about nothing! It is most likely true that when Liza's blood is retested, those values will be back to normal again. And then we will all relax. ;)

Marianne

[marinaliz]

I would like to add that before 12 days we had another blood test (before starting Vetoryl), and as far as I can remember, although I haven’t these results in my hand, my vet had not mentioned any abnormal kidney levels. I will ask him though.

In my hands I have another blood test which was carried out just one month ago (21/10/2015). In this test, her creatinine level was 0.78 (0.4-1.2).

[marinaliz]

Furthermore, in the abdominal ultrasound (24/10/2015) both kidneys appeared normal.

[labblab]

Those are both very good things. :)

So again, your vet is probably absolutely right about the dehydration. I apologize if I am worrying you too much! I know you have plenty of things to worry about without me adding to the list...

So just forget I've said anything and I'm confident that the bloodwork will be back to normal next time around, or nearly so. I will mention that I think Dechra mentions that BUN may run a little bit higher with dogs taking trilostane. It doesn't mean anything is wrong; it is just a lab change that can accompany the treatment.

[marinaliz]

Please do not apologize! It is reasonable to note anything that might be suspicious. And please let me assure you that I am much calmer now… You are all wonderful people and I feel so lucky having you by my side.

[labblab]

I am back again, and I found the old Dechra technical brochure that listed the possible biochemical changes that can be expected in a dog being treated with trilostane. Here they are:


Alkaline Phosphatase: Decrease but may not return to reference range

Alanine Aminotransferase: Decrease but may not return to reference range

Cholesterol: Decrease but may not return to reference range

Sodium: May decrease slightly but should remain within reference range

Potassium: May increase slightly but should remain within reference range

Urea: May increase slightly but should remain within reference range

Creatinine: May increase slightly but should remain within reference range

Red Blood Cells: May decrease slightly but should remain within reference range

As it turns out, my memory was correct that Urea (BUN) can increase slightly. The brochure says that creatinine can also increase slightly. However, as you see, those two values should still consistently remain within the normal reference range. So we shall be hoping and assuming that Liza's values will return to the normal range on the next testing, as well.

[molly muffin]

My vet doesn't worry as much about just BUN going up, unless it is alongside the creatinine. Even then it can be due to outside factors, and you want to keep an eye on it to make sure that it isn't trending upwards.

If there is any worry of kidney disease, there is a test that can be done that is more accurate for early detection, SDMA, which your vet could do. If that comes back normal then it is really likely nothing to worry about.

[marinaliz]

Hello!!! Liza is doing great and I wanted to share with you... In fact, I haven't see her so lively since the stroke. Diarrheas have been stopped. She is running, jumping etc., without falling down and losing her balance!!! Only in the morning she seems a bit weak but after 5 min she is almost completely ok. I can say now, after about 1,5 month from the stroke, that is almost 90-95% herself. I am so happy for my girl! In fact, I didn't expect such an improvement, especially after the last days which were really tough for her...And of course I have stopped doing experiments with her diet and I feed her with her old, ordinary food.

However, the increased urination/drinking thing unfortunately is still here... Tomorrow morning I will visit my vet so to have another blood test only for BUN and creatinine in order to ensure that everything is ok with her kidneys. I insisted for this blood test to be done. My vet insists not to worry...

In case that these levels are found normal what can I do? Maybe a higher dosage would decrease urination/drinking?

In case that these levels are not found in normal range, we can then say that Vetoryl damages her kidneys? Note that creatinine and BUN were both normal before 15 days. What I could do in this case? Trying a lower than 30mg dosage?

[marinaliz]

Today Liza took her 14th pill. I know that it is recommended to increase the dosage after 30 days and I will not hurry. However, I believed that with Vetoryl the symptoms would be decreased but as I can see they have been slightly increased during last days.

On the other hand, ALP has decreased significantly from 1400 to 670. Her baseline cortisol was in reference range (without previously taken Vetoryl). What is going on? I am confused again. Isn't a good sign that ALP drops? And why symptoms (drinking) increase?

Is there a possibility to minimize symptoms with a higher dosage? I was hoping that the 30mg would have a result but it seems difficult.

[labblab]

So glad to read such a good report on Liza, overall! I am sorry her thirst and urination are not yet any better, but it may just take some time for those things to improve. I know it is very hard to remain patient, but let's wait and see how all the test results turn out. Once we know for certain what the numbers turn out to be, it will help us narrow our focus on the possibilities. Truly, I think it's a big plus that Liza's behavior is otherwise improving so much. :)

Marianne

[marinaliz]

Hello! I am back again with the results from the blood test we performed this morning.

27/11/2015:
BUN 47,73 (9-24mg/dl)
Creatinine 2,36 (0,8-1,6mg/dl)

Previous results 22/11/2015:
BUN 79,09 (9-24mg/dl)
Creatinine 2,9(0,8-1,6mg/dl)

Eventually as it seems these values decrease. I have just spoken to vet who told me that is unlikely that Vetoryl damages her kidneys function. He attributes these high values to the diarrheas and he told me that, for a 14,5 year old dog, 10-15 more days are required for these values to return to normal range.

[marinaliz]

Could you please tell me what is the normal daily water intake (ml/kg) for a dog who eats dry food? Wherever I have searched on the Internet there are many different opinions...

[marinaliz]

Hello! I have found this on the internet "...Vetoryl is preferred in the Pituitary Dependent Hyperadrenocorticism (PDH) form of Cushing's disease, while Lysodern is administered in cases of the purely adrenal gland related form of Cushing's disease, which usually is a tumor over the adrenal gland..." Is this true?

I am really very worried, since we are on the 15th day of Vetoryl and symptoms (particularly excessive drinking) are still here.... In fact, I think that they have been slightly increased. Yesterday Liza drank 1lt/24 hours. I don't know what's going on here. Otherwise Liza looks really great and very happy.

Before taking prezolon, she was drinking approx. 700 ml/24 hours. Prezolon has been stooped over one month ago. On the other hand, before Vetoryl, ALP was 1200 and now has been reduced to almost 670. This could be an indicator that Vetoryl works positively. However, symptoms (drinking) seem to increase.

The thing that worries me mostly is the possibility of another stroke. Vetoryl is supposed to lower the cortisol levels in her body. If excessive drinking is an indicator that cortisol levels continue to be high, this increases the possibility of another stroke.

[lulusmom]

Hi and a belated welcome to you and Liza.

There is lots of stuff on the internet, a good deal which is outdated. There was a time when Lysodren was considered the best treatment for adrenal tumors because it was thought that it’s mode of action could shrink the tumor. There are really no studies that prove this to be the case but what is known is that adrenal tumors are highly resistant to Lysodren so extremely large doses are necessary which puts a dog a great risk of addison’s. I am very familiar with Lysodren and Vetoryl and if my dog had an adrenal tumor, Vetoryl would be my first choice every time. Even Dr. Edward Feldman, a renowned endocrinologist whose first choice of treatment of pituitary dependent disease is Lysodren, prescribes Vetoryl for his patients with adrenal tumors. I think you have Liza on the best treatment so that's one thing you can mark off your worry list. :D

I am ecstatic that your vet is ordering a stimulating agent for an acth stimulation test. I realize that the agent is hard to come by in Europe and we're always very concerned about our members abroad who are having to fly blind. Being uber vigilant, like yourself, is a must and you've done an excellent job....and so has Marianne and Sharlene in providing you with excellent guidance.

We'll be keeping fingers and paws crossed that the acth stimulation test yields some very good news for you and Liza.

Glynda

[molly muffin]

I think the rule of thumb for intake of water is an 1/2 ounce to 1 ounce per body weight. Anywhere in that range would be considered normal intake. Keeping in mind factors like dryness which causes them to be more dehydrated might cause them to drink more, or outside heat.

[marinaliz]

Thank you some much for your last replies. Liza yesterday performed the ACTH stimulation test, including all other necessary blood tests. Αs far as the samples of the ACTH test are concerned, again we sent them abroad for evaluation, so I think that I will be informed the results in more than 10 days by now. Otherwise, Liza seems very well and healthy.

However, I am very sad, desperate and frightened. Yesterday I visited another doctor who he claims to be specialized in Cushing’s. I don’t know if it was for good that I made this appointment. The news I have are bad. Let me list some of his concerns. In fact, he analyzed me three possible scenarios, with the third one being the most likely for him.

- 1ST SCENARIO: He doubts for the positive result of the LDDT. He believes that the result could have been affected by prezolon, although we have stopped giving it to Liza 10 days before the test. In this context, he told me that Liza may not have Cushing’s and the increase in the water intake may be a result of another illness or even from the prezolon. Furthermore, he mentioned that the nodules in her left adrenal gland may be incidental findings, benign and non-operational. I insisted at this point, that the blood tests after starting Vetoryl show a remarkable decrease of ALP that could not be incidental. That’s way I personally think that the possibility Liza not to have Cushing’s is unrealistic.

- 2ND SCENARIO: He also mentioned, that in case that Liza has Cushing’s, her LDDT results are consistent with the pituitary form of the disease (the same has Marianne already said). In this case the nodules in her left adrenal gland may again be incidental findings, benign and non-operational. However, now it’s really late to configure the type, since Liza has already started treatment. He said that a very small pituitary tumor may not be visualized in an MRI and that’s way we get clear MRI results.

- 3RD SCENARIO: He mentioned that Lysodren may be more appropriate for adrenal Cushing’s. Furthermore, the thing that worried me the most is that he said that if adrenal Cushing’s is the case for Liza, which is the most likely scenario, these nodules on her left adrenal gland are by almost 99% carcinomas and extremely metastatic… He stated that dogs with adrenal based Cushing’s have cancer which develops very rapidly. At this point I insisted that the levels of ALP for Liza are extremely high 1,5-2 years ago and she hasn’t any metastasis. He answered that the high levels during the previous years may be due to another reason (e.g. age, fatty liver etc.) and that adrenal based Cushing’s is something that occurred recently for Liza. He also mentioned that it is impossible that these high ALP levels during the last years to be associated with the adrenal based Cushing’s disease since in that case Liza should had shown the well known classic symptoms (clinical symptoms: pot belly, increased appetite, panting, excessive water intake and urination etc.). From the above, the only signs I had noticed were the increased appetite (while I am not sure if it was due to her character), frequent water intake (without panting or excessive urination) and another sign, i.e. anxiety and sometimes, which I don’t know if it could be attributed to the disease, when she was sitting calm she suddenly popped upright. This last sign had become such intense which had made me begun to wonder if I should give her any natural herbal sedatives.

I feel terribly sad today. I was so desperate of talking to someone so that’s why I am writing here. Sorry if I become tedious to post in many. I have a terrible feeling about how this situation is going to end. It’s very hard to know. Perhaps it’s better not knowing exactly the truth. It’s very hard to know that your puppy baby who looks inside your eyes with such love to have something in her body that kills her day by day and you cannot do anything.

[labblab]

You are not tedious at all! That is exactly why we are here -- for people to come and talk with one another, especially when they are feeling sad or frightened. So please write as much and as often you wish.

I am a born worrier, myself. So I can understand how difficult it is for you to live with so much uncertainty regarding Liza's true condition. It will indeed be very interesting to see how the ACTH testing turns out. Even though this new vet has told you that Lysodren might be preferred for adrenal Cushing's, I have to agree with Glynda that in recent years, we have been told here in the U.S. that trilostane is now the drug of choice for many specialists when it comes to treating the adrenal form of the disease. I think the most important thing for you to know is that it is not uncommon for trilostane to be prescribed for adrenal Cushing's, so Liza is not being treated in a manner that is strange or unusual.

I'm guessing that the hardest thing for you to deal with from this point forward will be the uncertainty as to exactly what is going on with Liza from day to day. Are the adrenal nodules growing and spreading, or are they not? Sadly, since you cannot perform an ultrasound every day, there is just no way of knowing the answer to this question without the passage of more time. However, I was struck by this sentence that you wrote above.


Otherwise, Liza seems very well and healthy.

This would not be an easy thing for me to do, myself (probably impossible, to be honest :o). But I am going to encourage you to try to focus on each day, one at a time. And to try as best you can to take comfort in seeing her behaving so well. Right now, it is impossible to know how many days like this she will have. But it is such a great gift that she has recovered so well from the stroke, and can have any days at all that are so enjoyable for her. Remember, she does not dread the future. She lives her life moment-by-moment. And I always think there is a lesson in that for us humans, too. It is a lesson I am still trying to learn, but I think it will be a blessing for me if the day ever comes when I can take that lesson to my own heart.

Anyway, please continue to update us and to write to us whenever you want to. And it is OK for you to continue to write about your sadness and your fear. I understand that they will never totally disappear for you. But my hope for you today is that you will be able to set aside the sadness for at least a little while, right now while Liza is looking so good.

Marianne

[marinaliz]

Marianne, I would like to thank you soooo much from the bottom of my heart for the positive energy you are sharing with me...although I was truly hoping that you would found something "incorrect" and "incoherent" in the new vet's 3rd scenario...

I am trying to do my best to think positive but its really hard to manage all these things. Unfortunately, I am also a born worrier and pessimistic. I had in my plans to perform another ultrasound in the days to come but I am afraid for the result. So I haven't decided yet if I am going to do another ultrasound or not.

I would like to also thank you and Glynda for the information about Lysodren and Vetoryl.

[marinaliz]

Hello again!

I have Liza’s results from 1/12/2015 blood test. Creatinine has been further decreased.

Creatinine: 1,81 (0,8-1,6 mg/dl)
Urea nitrogen (BUN) 44,55 (9-24 mg/dl)
Potassium 6,1 (3,5-5,5 nmol/l)
Sodium 160 (135-160 nmol/l)
ALP 693 (18-110 IU/L)
Cortisol 3.86 μg/dl

Unfortunately my vet made a mistake. On 1/12/2015 (17th day from starting Vetoryl) he took 2 blood samples. The first, prior ACTH injection, and the second, post ACTH injection. Liza had taken Vetoryl 4 hours before the first blood test. The sample “prior ACTH injection” was about to be also sent in a local Veterinary Laboratory (so to have more immediate results about Creatinine, BUN, etc.) while the sample “post ACTH injection” was about to be sent only abroad for evaluation. Unfortunately, the “post ACTH injection” sample was eventually sent in the local Veterinary Laboratory instead of going abroad… So, we must perform again the ACTH test in the next few days.

Thus, the results I post above come from “post ACTH injection” sample. Assuming that the lab results performed at home are valid, Liza’s Cortisol is 3.86 μg/dl. Could we draw any conclusions from this Cortisol level?

In the meantime I am very confused... On 22/11/2015 we had another blood test in the morning before Liza taking her daily dose of Vetoryl (due to the diarrheas episodes). Her Cortisol that day was found 4 μg/dl. Is it possible these two Cortisol levels (post ACTH injection vs Cortisol without taking any meds) to be almost equal?

[labblab]

Hi again! I'm very glad to hear that Liza's blood panel continues to normalize.

As for the post-ACTH level of 3.86 ug/dL -- if that is accurate, that is really a perfect result and I do not believe you would want to risk driving it any lower by increasing the trilostane dose, especially since her cortisol may still drop even a bit lower after a couple more weeks on this same dose. So I do not think that lowering her cortisol even further is the solution even if her excessive thirst and urination continue.

As for the earlier resting cortisol of approx. the same amount, I would not fret over that. Resting cortisols can vary considerably, even from hour-to-hour in the same dog. That's why they cannot be relied upon either to diagnose Cushing's in the first place, or to decide upon dosing increases. Their greatest value for Cushpups is perhaps ruling out a situation where cortisol has dropped too low. If a baseline cortisol has dropped below 2 ug/dL, it is possible that oversuppression is taking place and a full ACTH should be performed in order to assess more fully.

Marianne

[marinaliz]

Thank you Marianne for the information. I hope that the post ACTH result we have is accurate. I am planning another ACTH test during next week; however, I don’t know the suggested minimum time interval between two ACTH tests and if it is too soon to be performed the next week.

Liza seems happy and healthy. It seems that the increased urination has decreased, or she is more cautious not having “accidents” inside the house. We take her for a walk 3-4 times per day. Drinking has also been decreased but not as much as I would expect (yesterday she drank approx. 900 ml/24 hours).

As far as I’m concerned, I am a mess, that’s the best way to describe my feelings. If I haven’t done that ultrasound, I wouldn’t have known and it would be better. I have been searching through the internet all these days about the prognosis and related things… Unfortunately, I have also drawn some conclusions. The two best-case scenarios which I have described in a previous post are veeeeery veeeery unlikely for the following two simple reasons: 1) ALP has decreased from the day we started treatment with Vetoryl, meaning that something existed which is now more controlled. 2) Although results from LDDT were consistent with the pituitary form of the disease, what we have here is 2 masses in the left adrenal gland (from which the one is really big, 2,2cm). From my own research what I have understand is that when pituitary form is suspected both adrenal glands are enlarged, and not only the one (such as in our case). So, what we have is the remaining 3rd scenario, which has very poor prognosis. It is reported that the majority of such tumors are malignant and the size of the tumor is an indicator too (>2cm tend to be malignant, >4cm are almost always carcinomas). So I am sitting here and I am waiting to see a possible metastasis. Wow! I feel terribly bad, sad, I can’t even describe. I wish I wouldn’t have done this ultrasound. Thanks god, I have my little son here and we share moments of happiness because otherwise I would have become totally crazy.

[molly muffin]

Hi, it's really hard emotionally if you think too much about the adrenal nodules and what they might or might not be doing. The best thing is to just have regular ultrasounds to monitor them. That will give you the best idea of what is occurring. I do every 6 months, since my molly's hasn't changed.

[marinaliz]

Hello! Ι don't know where to start from...!!!

Here is a good update! First of all Liza is doing very well! Second, last week I sent by post (he lives 500km far from my home) all Liza's blood tests, MRI results, ultrasounds etc., which we have performed during last years, to a University Professor specializing in canine endocrinology. I have good recommendations for him. Actually, my vet recommended him to me as he considers him an expert in Cushing’s! He studied in detail all diagnostic tests and during the next few days he will send me officially his opinion. However, I have just spoken to him on the phone to give me a brief initial approach.

Here it is what he believes: The most likely scenario for him according to Liza’s diagnostic tests is that she has the pituitary form of the disease and the findings in the adrenal glands are incidental. He said me -among other things- that a characteristic feature of the syndrome due to an adrenal tumor is the atrophy of the contralateral adrenal gland, a fact which not exists in our case. Furthermore, he said that an MRI cannot always catch the pituitary tumor if it is very small. Also, as far as the drinking is concerned, he told me that he doesn’t care about the frequency of drinking but he cares about the total daily amount, which in our case, as he said, is on the top but still within the normal range. I do not know what to do ... to be happy or to be restrained… If this doctor is a specialist he may be right!!

[labblab]

Oh, I think this is all very good news, too!! :) :)

Everything this vet has said seems possible to me, and actually a very reasonable explanation for all the pieces of the puzzle. The fact that Liza is doing so well is wonderful, and hopefully makes it less likely that the adrenal nodules are causing her serious problems.

Thanks so much for giving us this good report, and I hope the written followup will provide even greater peace of mind!

Marianne

[marinaliz]

Thanks Marianne! I will let you know as soon as I get his written followup. Thanks for the support, thanks for everything!

On Monday we have scheduled the next ACTH test and routine blood tests to check also kidneys' function. I will keep you updated!

[molly muffin]

I think it all makes sense too. This is a good report. It's good to know what is going on most likely.
My specialist also told me that sometime the pituitary tumor is so small that an MRI will miss it. It's when they become large and you want to rule out a macrotumor causing neurological problems that they are most beneficial.

[lulusmom]

I think everything you were told by the professor is spot on, so that makes three of us who agree. Congratulations on getting some solid feedback from what appears to be a very qualified source. Please do let us know if there is anything in the written report that you haven't yet shared.

Glynda

[marinaliz]

Unfortunately, this time the news are not so good...

I have just be informed the results of yesterday's blood work. The level of ALP has been remarkably increased since the last blood test:

ALP 1451 (18-110 IU/L) 3 November 2015 (this was before starting Vetoryl)

ALP 669 (18-110 IU/L) 23 November 2015 (this was after approx. 7 days since we started Vetoryl)

ALP 693 (18-110 IU/L) 2 December 2015

ALP 1023 (0-90 IU/L) 14 December 2015

I would like to add that Liza still drinks a lot. Otherwise she looks fine. However, I know my dog, and I know that these water quantities are not normal for her. I am terrified... I have a bad feeling that things may not be as good as I have described my previous posts.

Can someone please tell me why Vetoryl seems that does not work for Liza?? Could it be an indicator that Liza has adrenal-based? Why ALP is increasing?

[labblab]

I am noticing that the "normal" reference range for this most recent ALP reading is different from the previous readings. So was this bloodwork sent to a different lab for analysis? If so, it is possible that lab variation might account for a bit of the difference from the last two lower results. However, it is unlikely that lab variation could account for all of the difference, so it would seem that there has again been an increase of at least some degree.

In honesty, though, I was quite surprised at the big drop in Liza's ALKP during the first two tests after starting Vetoryl. It is very unusual to see ALKP levels drop that much so quickly if Cushing's is the cause of the elevation. In fact, some dogs with Cushing's never see ALKP levels that totally return to normal, no matter how long they remain on Vetoryl. And even though Liza's ALKP is highly out of the normal range, her level is not unusual in comparison to many other dogs who also come to us here.

As a result, I am not sure how much significance or worry to attach to her ALKP level. I don't think it bears any relation to the type of Cushing's she suffers from. Elevated ALKP is simply a result of chronic elevated circulating cortisol, regardless of whether a pituitary or an adrenal tumor is the cause of the cortisol overproduction.

I know you are also concerned about the frequency of her drinking. But I believe this new vet has told you that her overall total fluid intake is really not higher than normal? If that is so, and if she otherwise continues to look well, I really don't know that the elevated ALKP is a major source of concern right now. You might check with the new vet and see what he thinks about this new test result.

Marianne

[marinaliz]

Thanks Marianne! I am back here to add some more details which I didn’t mention in my previous post because I was terrified about the increase in ALP.

Yes, this last bloodwork was sent to a different lab for analysis, I don’t know the reason. The day I was informed the results of the last bloodwork, I called immediately the Professor who told me exactly the same things with you about the levels of ALP.

But there were some more abnormal values which I didn’t mention in my previous post. Specifically,

14 December 2015:
Creatinine: 1,82 (0,5-1,4 mg/dL)
Urea nitrogen (BUN) 44,09 (10-32 mg/dl)
SGPT ALT 179,86 (10-94 IU/L)
ALP 1023 (0-90 IU/L)

1 December 2015:
Creatinine: 1,81 (0,8-1,6 mg/dl)
Urea nitrogen (BUN) 44,55 (9-24 mg/dl)
ALP 669 (18-110 IU/L)

23 November 2015 (this was after approx. 7 days since we started Vetoryl)
Creatinine: 2,9 (0,8-1,6 mg/dL)
Urea nitrogen (BUN) 79,09 (9-24 mg/dl)
SGPT ALT 121 (25-93 IU/L)
ALP 693 (18-110 IU/L)

3 November 2015 (this was before starting Vetoryl)
Creatinine: 0,91 (0,5-1,4 mg/dL)
SGPT ALT 132 (10-94 IU/L)
ALP 1451 (0-90 IU/L)

21 October 2015 (just few days after the stroke)
Creatinine: 0,78 (0,4-1,2 mg/dL)
SGPT ALT 189 (21-97 IU/L)

I really was terrified for the increase in ALP but as it seems I should not worry for this. Professor told me not to worry for ALP and dogs with Cushing’s may even reach 4000 IU/L. The thing that worries him the most (although not too much at this point) is her kidneys. In our first communication (about 1 week ago) he had told me that I should change her food (again) and feed her with renal failure diet which I haven’t done since the day before yesterday because I was afraid to change again her diet. Moreover, most of renal failure dry foods contain chicken, on which Liza is allergic! So, just after I received her last bloodwork results, I went to the pet shop and eventually I found a dry food which protects renal function and does not contain chicken. So Liza eats her new food since the day before yesterday without any problem.

About water consumption: Professor told me that polydipsia in a dog is considered above 100 ml/kg (per 24 hours).
Liza, before the stroke (about 2 months ago) and for the last few years, was drinking 500-600 ml per 24 hours (which is 40-50 ml based on her weight, 12kg). After the prezolon, she immediately increased the water intake to more than 1000 ml (which is 83 ml/kg) and she urinated too many times per day. All these days she was drinking between 800-1000 ml per day, which worried me because I know my dog and I know that this amount is not normal for her although Professor considers this amount on the top but still normal. Anyway, I don’t know if this increase in water consumption is caused from Cushing’s, from prezolon or from her kidneys abnormal function BUT yesterday she drank, for the first time since the stroke, 650 ml (which is 55 ml/kg), which is very normal. Maybe her new food caused this reduction, or maybe it just occurred, I don’t know. I will keep watching her closely.

Later today, I will post the official report I received by the Professor concerning her Cushing’s and all the other things he mentions.

[marinaliz]

I am back again… I hold in my hands Professor’s written report. I will try to make the translation word by word. Because the report is lengthy, I am going to translate only two parts: 1) the Cushing’s issue and 2) the kidney’s issue.

1) Based on the study of clinical progression and the systematic long-term laboratory tests I am convinced that "Liza" is suffering from pituitary hyperadrenocorticism (Cushing's syndrome or PDH) due to a functional micro-adenoma of the anterior / medial lobe of the pituitary, which is not shown on the MRI of the brain. Treatment with Vetoryl started at the right dose, which may be changed to 12-hour dosing or at higher or lower daily dose depending on the expected result of the ACTH stimulation test (the samples must be sent abroad for evaluation).

The diarrhea after starting treatment was probably due to a sharp drop in blood cortisol which is gradually being restored. As far as the ultrasound of the adrenal glands is concerned, personally I do not see a significant difference in size between the two adrenals. Note that in the pituitary hyperadrenocorticism adrenal glands can either appear normal or hypertrophic (with or without symmetry). Hypertrophy can be simple or nodular. The latter could develop into adenoma. In my opinion, the relevant finding in this dog does not mean that the dog suffers from adrenal HAC (ADH).

2) I believe that the observed azotemia is due to chronic renal failure (CKD), for the treatment of which the dog should be fed with some good quality Renal diet and having checked at regular time intervals the levels of creatinine, BUN and phosphorus in the blood serum. Simultaneously, the glucose, the enzymes of the liver and the blood pressure (arterial) should be checked.

[marinaliz]

In my first posts here in this forum, Marianne has mentioned that the results from the LDDT are consistent with the pituitary form of Cushing's. I have also made a research on the Internet and I have read some publications concerning the Interpretation of Laboratory Tests for Canine Cushing’s Syndrome.

Below I summarize the three LDDTs we have performed.

July 2014:
LDDT:
Cortisol (1st sample) 4.01 (0.7 – 9 μg/dl)
Cortisol (2nd sample) - 4 hours 0.35
Cortisol (3rd sample) - 8 hours 0.43
Vet said no cushing’s

June 2015:
LDDT:
Cortisol (1st sample) 5.3 (0.7 – 9 μg/dl)
Cortisol (2nd sample) - 4 hours 0.96
Cortisol (3rd sample) - 8 hours 0.8
Vet said no cushing’s

November 2015:
LDDT:
Cortisol (1st sample) 151 (20 – 250 nmol/L)
Cortisol (2nd sample) - 4 hours 40.3
Cortisol (3rd sample) - 8 hours 58.7
This time the above samples were sent abroad for evaluation (I think in the U.K.) and eventually Cushing’s confirmed.

Looking the above numbers, if I have understοοd correctly the Interpretation of Laboratory Tests, Professor Diagnosis could be correct. I would like to note two things:

First that, in all three tests, Liza showed remarkable cortisol suppression, despite if the test was positive or negative for Cushing’s. I have read that in most adrenal forms cortisol suppression does not occur because ACTH secretion is already suppressed.

Second, I have read that if at least one of the following criteria is met (assuming that the 8-hour serum cortisol concentration is above the diagnostic cutoff and the diagnosis of Cushing’s has been made), the diagnosis of PDH can be made and no further tests are needed.

1) A cortisol measurement at 4 and/or 8 hours that is <50% of the baseline cortisol (LIZA HAS BOTH VALUES <50%)
2) A cortisol measurement at 4 hours that is below the diagnostic cutoff (<40 nmol/L) (LIZA HAS 40,3)

Finally, I have read that in dogs with PDH, the abnormal corticotrophs quickly escape suppression by dexamethasone and resume secretion of ACTH within less than 8 hours, thus stimulating cortisol secretion from the adrenal cortex and leading to increased serum cortisol concentrations and a positive LDDST result (>40 nmol/L at 8 hours) (LIZA HAS 58,7).

From your experience, could the above findings strengthen Professor’s opinion that Liza has PDH? These findings could be really considered determinant for PDH? Is it possible a dog with adrenal-based to have these test results?

I am really sorry for today; I have posted so many things…but I have so more in mind. Sorry if I become tedious.

[Harley PoMMom]

Yep, Liza most recent LDDS test results are indicative to the pituitary form of Cushing's. Some of the concerns I have are most definitely the continued rise in her creatinine, although the creatinine was normal before starting the Vetoryl is was still trending upward. In most animals 50%-70% of kidney function is lost before elevations are seen in the creatinine. Vetoryl can unmask kidney issues, that happened with my Harley. My other worry is that with the LDDS test any non-adrenal illness can cause a false positive result and since her creatinine was trending upwards I'm fearful that those LDDS test results could be falsely elevated.

With my boy, Harley, I added wild salmon oil as it has anti-inflammatory properties. There is a debate that CoQ10 can decrease the creatinine so I would probably add this supplement too but only with the vets approval.

Hugs, Lori

[marinaliz]

Thanks Lori for the reply. In fact, that I was also told by the Professor. He believes that Liza suffers from chronic renal failure although her blood tests during the last two years are normal. However, I have in my hands, a test which was made in 2012. Creatinine was 1,93 (0,8-1,6mg/dl). I did nothing, and after some days the level was decreased to normal. Since then, creatinine was always within the reference range. Professor also saw these tests results.

I am sorry for your boy... I suppose that you discontinued Vetoryl after his kidney issues were unmasked?

I will ask for wild salmon oil the vet. From where may I get this? Also if there is something else I have to give her with her food or a medicine perhaps, I would be grateful to know.

The confirmative to Cushing's LDDT was performed within November. By that time her creatinine levels were normal. However, if Liza had a subclinical form of kidney failure, and this caused a false positive result, things become more complicated.

My next step is to call my regular vet and repeat her blood work during next week. Another solution could be to stop Vetoryl for a long period of time and repeat LDDT. However, I am afraid to do this and the reason is another stroke. If Cushing's caused her this stroke and if the decease is left untreated a possibility of a new stroke is high.

[Harley PoMMom]

For the salmon oil I used Monica Segal's brand, here's a link to it: http://www.monicasegal.com/Wild_Salmon_Oil.html She also sells CoQ10: http://www.monicasegal.com/CoQ10.html

I wouldn't bother repeating the LDDS test. I did see in one of your posts that her most recent ACTH stim test had to be done over, since then has Liza had her cortisol checked with the ACTH stimulation test?

Hugs, Lori

[marinaliz]

Thanks Lori! The ACTH stimulation test was performed on 14 December. Unfortunately, I expect to have the results in more than 10 days by now (maybe even in the first days of 2016) because we have sent the blood samples abroad for evaluation.

[molly muffin]

I would have them do an SDMA test on her kidneys and see if she indeed has renal function problems or if it is the medication causing the abnormalties in the creatinine. We had the same worries and the SDMA is the newer test and able to detect kidney disease much earlier than the other tests out there.

[marinaliz]

Hello! I have just received from abroad the ACTH sim test results:

Cortisol 44,4 nmol/L (20-250)
Cortisol Post 172 nmol/L (60-550)

Yesterday we made another blood test and its results are:

23 December 2015:
Creatinine: 1,29
SGPT ALT 180
ALP 1150

An here are the results from almost ten days ago:
14 December 2015:
Creatinine: 1,82 (0,5-1,4 mg/dL)
Urea nitrogen (BUN) 44,09 (10-32 mg/dl)
SGPT ALT 179,86 (10-94 IU/L)
ALP 1023 (0-90 IU/L)

I am giving her renal diet food which seems that worked well since creatinine levels were dropped to normal range. I am going to repeat the blood test next week to ensure that everything is ok.

As far as the results of the ACTH test, as I can see from dechra's monitoring chart we are in the mid, and they suggest to continue at current dose but monitor clinical signs for recurrence. Liza seems really good, however, her drinking quantities are approx. 65 ml/24 hours (or approx. 800ml/24 hours), meaning that she needs to go for a walk at least 4 times per day. On the other hand, increasing the dosage before ensuring that everything else has been stabilized (creatinine etc.) I don't know if it would be a good idea.

[molly muffin]

At 172, you could see if the drinking will lessen with some time or not. If not, then it's possible that the dose might need to be increase, but again as you mention you are going to want to see how the kidneys are functioning, as the drinking might not be due to cushings but to kidney problems.

[marinaliz]

Thanks Sharlene! I would like to ask some things, if someone can answer, it would be really helpful, because I worry again...

Liza still drinks a lot, the total daily amount is high but not extremely high. On the other hand, the frequency of drinking is very high, she maybe drink five times and even more within one hour. And she constantly asks for food. However, the eating thing could be partially a part of her character, since as long as I remember, she always loved food. In any case however, there is a high possibility, at 172, that she needs a dosage increase. Now she takes 30mg. How it sounds giving her 45mg (once daily)?

The next thing I would like to ask is if the Cushing's problem is proportional to the dosage. In other words, dogs that have large tumors (adrenal or pituitary) need a higher dosage?

Tomorrow I will take Liza to her regular vet to make another blood test. Checking only the creatinine is enough? If creatinine level is still within normal range is it safe to increase the dose of Vetoryl?

I would like to mention that except of the drinking thing, she looks very happy and healthy.

[marinaliz]

Hello again! Just came back from my regular vet. He insisted that having an extra blood test for checking creatinine is not necessary in such short period since the last result was 1,29mg/dl on 22/12/2015.

Anyway I would like your opinion on how to move on with her treatment, and more specifically with her Vetoryl dosage.

The fact is that the 30mg I am already giving once daily to Liza is not controlling her clinical signs. She is all day anxious, asking for food, asking to go outside to urinate and from yesterday she started peeing inside the house. The professor suggested to give her Vetoryl 30mg twice per day. On the other hand my regular vet suggested me to increase the dosage of Vetoryl to 50-60mg once daily thinking that since clinical signs are not controlled in any part of the day it would be worthless to divide the increased dosage of 60mg.
Could you please advise me how should I move on and how much shall I increase the dose of Vetoryl?

Thanking you in advance.
Wishing you all the best and happy new year!!

[labblab]

Hello! I am really sorry that Liza's symptoms seem to be worsening again. However, based on her recent monitoring ACTH results, I do not think it is safe to fully double her daily Vetoryl total. For the benefit of our U.S. readers, these are the converted values for her ACTH test:

Pre-ACTH: 1.6 ug/dL

Post-ACTH: 6.2 ug/dL

This post-ACTH value is only a tiny bit above the desired therapeutic range of 1.45 - 5.4. Therefore, I believe only a small dosing increase is safe -- perhaps an additional 10 mg., but I would go no higher right now. As to whether you want to add the extra capsule to the morning dose or give it separately in the evening, I would say you can do whichever better suits your schedule and also Liza's meal schedule since Vetoryl should be given with food. There does seem to be research evidence that twice daily dosing may end up keeping overall daily dosing needs at a lower level, presumably because cortisol levels remain consistently "flatter" throughout an entire 24-hour time period. However, your regular vet's advice does correspond with Dechra's dosing recommendations -- stick with once daily dosing unless symptoms remain unresolved even when the post-ACTH level is below 5.4 ug/dL. So there is support for either dosing decision.

Most importantly, though, regardless of her thirst and urination, I believe you have to pay attention to Liza's ACTH results and not proceed with an excessively high increase in her Vetoryl dosage. To be safe, it is better to gradually increase the dose in order to avoid creating the opposite problem -- a cortisol crash and an Addisonian condition.

Marianne

[marinaliz]

Thanks Marianne for your immediate response.

So, if I have understood correctly, I have two options, since you suggest an increase of 10mg to the overall daily dosage (i.e. 40mg/daily total). The first is to give Liza 20mg every twelve hours (always with food) while the second is to give her 40mg once daily (e.g. in the morning with her food). Am I right?

[labblab]

You can either give Liza 40 mg. in the morning, or in order not to waste your 30 mg. capsules, you can keep giving a 30 mg. capsule in the morning and add a 10 mg. capsule in the evening. Dechra's newest dosing recommendations say that you do not have to give equal doses if you shift to a twice-daily regimen. But if unequal, the larger dose should be given in the morning. And monitoring ACTH testing should proceed as before: 4-6 hours after the (larger) morning dose.

[marinaliz]

Ok, many thanks! I have already ordered the 10mg capsules and I will have them hopefully tomorrow morning. I feel, as you do, that it is safer to make a conservative increase especially these days that most vets are on holidays...

However, I am a little bit confused about the twice daily dosing. This is because I see that her clinical signs, with the 30mg dosage, are not controlled in any part of the day. I am thinking that if I keep giving her 30mg in the morning and adding 10mg in the evening it won't make any difference.

[labblab]

When shifting to twice-daily dosing from once-daily dosing, you are always basically cutting the daily total in half (or in segments if you can't split exactly in half) rather than doubling it. Since trilostane's effectiveness in the bloodstream generally does not exceed 12 hours at most, I believe the rationale is that cortisol levels will not have the opportunity to "spike" as highly at any time during the 24-hour time period if at least some of the medication is effective at all times. So in other words, if you give the sole "whole" dose in the morning, by evening, the cortisol level will have the opportunity to spring back upwards after the effect of the drug has worn off. Whereas, if some amount of the medication is given every 12 hours, the cortisol is never allowed to rebound as highly and there is some degree of effective control at all times.

Each dog will metabolize the drug a bit differently, however. For some dogs, the single morning dose does effectively keep symptoms controlled all day. For other dogs, cortisol seems to rebound more quickly and so symptoms return in the evening even though cortisol is well controlled in the morning. There is really no way to know in advance which regimen will suit any given dog better. I think Dechra recommends starting out with the single morning dose partly just for greater ease in dosing. It is easier for owners to comply with that regimen, and if a dog does well, why make things any harder? But for dogs who are not well-controlled on the single dose, then dosing twice daily may keep the cortisol more efficiently controlled at all times. For Liza, it may be the case that if her cortisol drops lower in the morning on a higher once-daily dose, her symptoms will resolve throughout the entire day. But if not, then shifting to twice-daily dosing may help.

[marinaliz]

Ok, once again thank you very much! I think that now it is more clear to me how to proceed. Tomorrow I will give her 40mg in the morning with her food and see how she goes. I will keep you updated.

[molly muffin]

Eventually when through these pills, you might be able to do 20mg am and 20mg pm, which would probably be more optimal, but if you are not doing an even split then they suggest usually the higher in the morning.

I give once a day but it depends on many factors, like how the dog does throughout the entire day.

[marinaliz]

Unfortunately I have some bad news. I would appreciate any advice you could give me since I can not get persuasive answers from my vets. I will post some results below.

22 January 2015
HCT 45,3 (37,0-55,0%)
PLT 760 (175-500)

21 October 2015 (just few days after the stroke and before starting Vetoryl)
HCT 41 (37,1-57,0%)
PLT 760 (175-500)
Creatinine: 0,78 (0,4-1,2 mg/dL)

3 November 2015 (this was just a couple of days before starting Vetoryl)
Creatinine: 0,91 (0,5-1,4 mg/dL)
SGPT ALT 132 (10-94 IU/L)
ALP 1451 (0-90 IU/L)

23 November 2015 (this was after approx. 7 days since we started Vetoryl)
Creatinine: 2,9 (0,8-1,6 mg/dL)
Urea nitrogen (BUN) 79,09 (9-24 mg/dl)
SGPT ALT 121 (25-93 IU/L)
ALP 693 (18-110 IU/L)

1 December 2015:
Creatinine: 1,81 (0,8-1,6 mg/dl)
Urea nitrogen (BUN) 44,55 (9-24 mg/dl)
ALP 669 (18-110 IU/L)
16 December 2015:
Pre-ACTH: 1.6 ug/dL
Post-ACTH: 6.2 ug/dL
Creatinine: 1,82 (0,5-1,4 mg/dl)

17 December 2015: I started giving her renal diet food.

22 December 2015:
HCT 39,1 (35,0-57,0%)
HGB 13,7 (12-18 g/dl)
RBC 5.980.000 (5.500.000-8.500.000 μl)
MCV 65,4 (66-77)
MCH 22,9 (21-26 pg)
MCHC 35 (32-36 g/dl)
WBC 7330 (5000-14000 μl)
Neutrophils 5131 (3000-12000 μl)
Lymphocytes 1319 (1000-5000 μl)
Mononuclear 733 (150-1350 μl)
Eosinophils 146 (100-1250 μl)
PLT 661.000 (200.000-700.000 μl)
Creatinine: 1,29 (0,5-1,7 mg/dl)
ALP 1150 (1-114 U/L)
Phosphorus 4 (2,9-5,3 mg/dl)

29 December 2015: Ι increased Vetoryl dosage to 40mg/24hours.

8 January 2016:
HCT 37,5 (37,0-55,0%)
RBC 6,00 (5,5-8,5 x 10^6 /μl)
HGB 11,6 (12-18 g/dl)
MCV 62 (60-77)
MCH 19,3 (18,5-30,0 pg)
MCHC 30,9 (30-37,5 g/dl)
WBC 8,0 (5,5-16,9 x 10^3 /μl)
Neutrophils 5,83 (2,0-12 x 10^3 /μl)
Lymphocytes 1,46 (0,5-4,9 x 10^3 /μl)
Mononuclear 0,5 (0,3-2 x 10^3 /μl)
Eosinophils 0,15 (0,1-1,49 x 10^3 /μl)
PLT 1217 (175-500 x 10^3 /μl)
MPV 7,9 (7,6-10,8)
Urea nitrogen (BUN) 21,36 (9-24 mg/dl)
Potassium 5,9 (3,5-5,5 mmol/l)
Sodium 154 (135-160 mmol/l)
Creatinine: 1,40 (0,8-1,6 mg/dl)
ALP 916 (18-110 U/L)

Based on the above blood tests you can see that HCT has been reduced significantly. Also, PLT has increased too much. Meaning? Maybe cancer… I say. My vets don’t worry, BUT I WORRY! I will repeat the blood test within the next week but my feeling is bad. I feel that the life of my dog is hanging by a thread and I’m afraid that my vets can do nothing. I should mention that -at least for the moment- Liza seems happy, she asks for food, she runs etc. She drinks approx. 650 ml/24 hours (or 54 ml/kg).

Please help me.

[marinaliz]

I would like to add to the above that I am planning not giving her tomorrow Vetoryl. Is it possible Vetoryl to cause these abnormal values in HCT and PLT? As you may see within about two weeks (since I increased the dosage) PLT has almost doubled.

Furthermore, I would like to ask if there is specific medication for the increased PLT value. I suppose that with this high result the possibility of thrombogenesis is increased. In humans I do know that in such situations doctors prescribe anticoagulants (like aspirin). My vet told me that there is not such medication for dogs and we can't give her anything.

[molly muffin]

I found one study out of the University of Guelph (animal vet teaching hospital) that showed that dogs with cushings, had higher platelet counts than dogs who did not. During treatment, while they seem to go up/down a bit, they in general seem to remain in the same range.

http://onlinelibrary.wiley.com/doi/10.1111/jvim.12162/pdf

So I can't really answer your question as to whether it would cause it to go up, treatment should either lower or keep more controlled it seems from reading that paper.

Maybe some of the others will have more thoughts on it.

[labblab]

I honestly would not worry about the HCT because it remains within normal range and it really does not seem to be all that much lower than the last lab check (37.5 from 39.1). Dechra's publications say that RBC counts may lower while being treated with Vetoryl, but it is not a cause to worry as long as they remain within normal range. So if RBC may lower, perhaps HCT does, too.

Also, regarding both the HCT and the PLT, it looks to me as though a different lab was used for this most recent testing because the "normal" ranges differ somewhat. If so, that could also account for some of the variability in the results. I will agree that the PLT count is significantly higher, though, and for that I'm afraid I really do not have any explanation, nor do I know whether it is a genuine worry. However, here is a blog that discusses some possibilities. Of the most comfort are the statements that a high platelet count is often meaningless, or is actually an error due to false automated laboratory cell counts. I am not sure that you will want to discontinue Liza's Vetoryl long-term just on the basis of this one elevated result.


A higher than normal blood platelet count is quite rare. It is usually of no significance. Platelet counts are often a bit higher in immature pets. Ironically the same cancers (lymphoma and leukemias) that can cause thrombocyte numbers to decrease occasionally cause them to increase. Thrombocyte numbers are sometimes elevated in inflammation of the digestive tract and its accessory organs, the pancreas and liver (IBD, Pancreatitis). Platelet counts are occasionally high due to the high cortisol levels of Cushing's disease as well. Corticosteroid medication can have the same effect. Hypothyroidism has occasionally been associated with elevated thrombocyte levels. Very rarely, the bone marrow megacaryocytes that give rise to thrombocytes will themselves become cancerous - multiply and overproduce thrombocytes or the whole marrow system will go into "neoplastic overdrive" (Polycythemia vera). When blood samples are hemolized, automated counting systems can mistake RBCs for platelets, giving falsely high counts.

http://www.2ndchance.info/dxme-Platelets.htm

[marinaliz]

Thank you both for your replies. It's Saturday morning and I haven't give her Vetoryl yet. I can understand that the reduction of HCT maybe due to the drug but I cannot understand (and perhaps no one can do) the sudden increase (within two weeks) of platelet count.

In any case however, could you please advise me what it means to discontinue treatment for a couple of days? Am I going to harm her? And if I decide to start again the drug after three-four days shall I give her the same dosage or lower?

[labblab]

Again, I am not a vet. But no, I don't think there will be harm from withholding the trilostane for a few days other than a possible return of Cushing's symptoms -- with one possible exception. Liza has already suffered one stroke from a clot. If her platelets are truly elevated, I believe this increases the risk for clots, as does elevated cortisol. So if the platelet count is not being caused by the trilostane, then stopping the drug may be a poor idea, especially since outwardly Liza is doing so well right now. As Sharlene has already pointed out, lack of Cushing's treatment seems to be associated with high platelets rather than the reverse.

Since you are concerned about the platelets, though, I would ask your vet to contact Dechra in order to gain their thoughts about this. In the meantime, if you do decide to halt the drug, I would start back again at the same dose. At this point, you really have no proof that the platelet count is a genuine problem or that the trilostane is the cause. So I would hate to see Liza's Cushing's treatment compromised due to a supposed problem that doesn't really exist.

Marianne

[marinaliz]

Ok, Marianne thanks. I think that I will give her the meds at least for today and I will repeat the blood test on Monday I hope. Indeed outwardly she looks so well and she drinks less.

The reason that I wanted to stop the meds for a couple of days was her reduction in HCT. If you see in her last lab test except of the HCT, the HGB was 11,6 (12-18 g/dl). If we consider that the real HCT maybe calculated from 11,6x3= 34,8% and not 37,5%. This is quite lower from the reference range and indeed may have been caused from the drug. But I think that anemia (in humans) may be a reason form PLT increase (although I am not sure) and this in turn increases the risk for another clot. I am so confused.

Can I call/email dechra on my own?

[labblab]

Unfortunately, our experience has been that outside of the U.S., Dechra prefers to speak only to vets. Having said that, you can still try to send an email. I just checked their website, though, and they do not maintain a corporate office in Greece. So their main U.K. headquarters may be your best bet, but you can see what you think. Here's their corporate homepage; you'll see a drop-down menu for "Countries" in the red block:

http://www.dechra.com/

[marinaliz]

ok, many thanks. I am writing an email right now and I will send it to the U.K. headquarters. I hope that I will get an answer. I'll keep you updated.

[molly muffin]

One of our admins sent me this link.

http://veterinarynews.dvm360.com/increased-number-platelets-call-review-thrombocytosis.

So I do think a specialist should look into the platelet issue if possible.

[labblab]

Yes, if the problem persists, I would send an inquiry to the specialist with whom you've been consulting. It seems to me as though there are two separate issues with which you are dealing. Are the elevated platelets genuine and a cause for concern? If so, does the Vetoryl help or hurt the situation? Dechra can perhaps help with the second question, but not as much with the first.

[marinaliz]

I have not yet any news from Dehcra. I have spoken to the Professor who told me to repeat the blood test and if PLT continues to be too high to go for an ultrasound.

Thank you for the link. It is written that "Some chemotherapy drugs exert their effects directly on dividing cells in the body - including the bone marrow where platelets are produced. When the body is recovering from the effects of such chemotherapy, a transient overproduction of some cells can occur, too." Is Vetoryl in this category? I suppose no.

Furthermore, I am wondering if there is specific medication for the increased PLT value. Do you know such medication? In humans I do know that in such situations doctors prescribe anticoagulants (like aspirin). My regular vet told me that there is not such medication for dogs and we can't give her anything.

[Harley PoMMom]

I would like to add to the above that I am planning not giving her tomorrow Vetoryl. Is it possible Vetoryl to cause these abnormal values in HCT and PLT? As you may see within about two weeks (since I increased the dosage) PLT has almost doubled.

Sharlene is correct in that Cushing's causes the PLT to increase in humans as well as in cushdogs.


Furthermore, I would like to ask if there is specific medication for the increased PLT value. I suppose that with this high result the possibility of thrombogenesis is increased. In humans I do know that in such situations doctors prescribe anticoagulants (like aspirin). My vet told me that there is not such medication for dogs and we can't give her anything.

My boy Harley's PLT was high too, his IMS and GP were in total agreement that he be given aspirin.

Hugs, Lori

[marinaliz]

hello!!!

Just finished with the ultrasound. The examination this time was performed by another radiologist who is considered one of the best in Athens. In fact, I was really afraid to make again this ultrasound but eventually I have some VERY VERY VERY GOOD NEWS!!!!

He writes in his report that it is obvious that Liza has the pituitary form of the disease. No masses exist in none of her adrenal glands. Both adrenal glands are shown with increased dimensions, with the left one being slightly bigger than the right one but he is sure that these findings are consistent with pituitary Cushing's. In any case, no tumors exist and he said that he strongly disagree with the diagnosis of the previous radiologist.

As far as the HCT and the PLT are concerned (although I don't have them in written yet, my vet informed me on the phone): On Monday we remade the blood test and the new results are:

HCT: 39,2 (increased)
PLT:670.000 (decreased)

From Dechra I have not any news yet but they told me that they are going to answer me the next few days. In any case, this sudden increase in PLT was due to the drug or the automated counting system gave us a falsely high count.

Also, I have stopped Vetoryl for 4 days. I will make another blood test tomorrow and if everything is ok I will restart treatment in the weekend.

[molly muffin]

What was the result of the follow up blood test? I'm wondering how she is doing. Did Dechra ever get back to you?

[marinaliz]

Thanks Sharlene. Yes they answered me. They told me, although they are not allowed to give general advice to pet owners, that Vetoryl may cause a decrease to some of haematological parameters but it is impossible to increase platelets. Specifically, they told me that “The product should be used with extreme caution in dogs with pre-existing anaemia as further reductions in packed-cell volume and haemoglobin may occur. Regular monitoring should be undertaken.”

I have made two more blood tests:

12/1/2016:
RBC: 5,52 x 10^6 cells/μL (5,5-8,5)
HGB: 12,5 g/dL (12-18)
HCT: 39,2% (37-55)
PLT: 679 x 10^3 cells/μL (175-500)

16/1/2016:
RBC: 5,27 x 10^6 cells/μL (5,5-8,5)
HGB: 12,5 g/dL (12-18)
HCT: 37,1% (37-55)
PLT: 664 x 10^3 cells/μL (175-500)

From the above, it is obvious that the high result of PLT (1217), which I got on 8/1/2016, was fortunately a falsely high count of the lab!

However, although I have stopped the drug since 10/1/2016, I was expected in these two recent blood tests to saw a slight increase of these numbers. I will going to make another blood test this Thursday, hoping for an increase so I can restart treatment. Also I should mention that during the last month Liza eats strictly her renal diet food and nothing else, thus she has almost no protein in her diet. I hope that the food, in combination with the drug, have cause these abnormalities in her general blood results. On top of that, she looks fine, although I think that some of her Cushing's clinical signs have returned (anxiety, increased water consumption). I don't know what to think. We have a good ultrasound, with no cancer in none of her organs. The next move, in case that the blood parameters remain too low, will be to draw blood from her bone narrow and to make a chest x-ray.

Any thoughts?

[labblab]

I am honestly not sure why you feel so worried about Liza's blood values since, although they are at the low end, they remain within normal range. In fact, I am wondering whether you may be contributing to lower red cell counts by scheduling such frequent blood draws. For such a small dog, losing blood so frequently may be contributing to the lower counts. Here's an article about hospital-induced anemia in humans, and I would expect the same thing is true for dogs.

http://www.medscape.com/viewarticle/747875

I just checked back, and Liza had blood drawn on all these dates, and perhaps even more.

November 23
December 1
December 22
January 8
January 12
January 16
And now, perhaps on January 21

I would think that the combination of the low protein food, frequent blood draws, and effects of the trilostane could jointly account for the lower red cell counts. But again, they remain right near normal range so I would not dwell on it for the time being. If Liza was mine, I definitely would not subject her to yet another blood test on Thursday, nor would I consider putting her through a painful bone marrow test right now.

Plus, it is no surprise that her Cushing's symptoms are rebounding without her medication. If it were me, I would resume the Vetoryl as before, and hold off on any more blood work for at least a month if not even a bit longer in order to allow her body to replace all the cells that have been drawn off recently. You have said repeatedly that she outwardly appeared to be doing well while taking the Vetoryl. I would not want to jeopardize that any longer by continuing to withhold the drug when her cell counts are still within normal range.

Marianne

[marinaliz]

Marianne you are the voice of reason! Thanks for your reply. I know that maybe I'm overreacting but character doesn't let me to see the glass as half full. I am pessimist by nature.

These high and sudden reductions in her blood results honestly made me scared and think that something else bad is coming... Every week during the last three months we have something new. At first it was the stroke and the scary thing of a possible brain tumor. Then, we had all the Cushing's clinical symptoms to appear literally from the one day to another, due to Prezolon. Then we had the adrenal nodules, for which I was told that there is high possibility to be cancerous due to their size (I am really wondering now how is it possible to be disappeared. The only explanation I have is that during the first ultrasound, Liza was taking Prezolon which may have caused these abnormalities in her adrenal glands-my thoughts). Then, we had the diarrheas episodes and the kidneys' problems with the elevated creatinine (by the way creatinine has now stabilized around 1,3 and the BUN 15). After that, we had the huge PLT increase, which eventually it was due to labs' fault. And now we have these reductions in HCT, RBC and HGB...

I am thinking -as you suggested- to hold off the extra blood work on Thursday and to restart the drug. I am pending also the result of the last ACTH test to see the levels after the slight increase I made from 30 to 40mg/24 hours.

It never crossed my mind at all that the frequent blood draws could contribute to the lower red cell counts. In fact, I believed that the quantity of the blood drawn each time is too small to affect the results...

Anyway, once again I would like to thank you, and more specifically, I'm thanking you on behalf of Liza for the time you spend each time to write your thoughts! You are all really wonderful people!!!

[labblab]

I am a worrier, too, so I do understand! But right now, it really seems to me as though the recent news you've received about Liza has been good news, combined with the fact that she seems to be feeling well while taking the Vetoryl.

Now, I cannot know for a fact that the blood draws have had an effect on her red cell counts. But I do believe the same size sample is needed for analysis regardless of the size of the dog. So a tiny girl like Liza is giving up a greater proportion of her blood with each and every test tube than is an 80-pound Lab like my Peg. Certainly, if your vets think that Liza should be tested sooner, you should ignore my advice. But as I say, under these circumstances where it could be expected that Liza's red cell counts would be found at the lower rather than the higher end of the normal range, I would personally give her (and yourself!) a temporary break from the testing. If her results in a few weeks have dropped even lower, then you may have reason to investigate further. But for now, I'd try to enjoy the good news you've been receiving. :)

Marianne

[marinaliz]

Hello!

I have just received the results of the ACTH test which was performed to check Liza's levels after the small increase of the dosage (from 30 to 40mg once daily).

Pre: <27 nmol/L (20-250)
Post: 84,7 nmol/L (60-550)

By the way, we performed and an x-ray of her chest and everything is normal.

Unfortunately, we have run out from the ACTH substance and I'm afraid that it will be impossible to check her levels again through this test into the near future. My vet used Synacthen of 0,25mg in the two previous tests. But I have found Synacthen of 1mg. I am wondering if it is the same substance and can thus be used for future testing. My vet told me that maybe the substance of 1mg is not the same as the 0,25mg and we cannot use it. Do you have any ideas for this?

[labblab]

Hi again! That's great that the x-ray results were good. :)

Also, that post-ACTH result (which converts to approx. 3.1 ug/dL here in the U.S.) is excellent! The pre-ACTH result is <1.0 ug/dL which seems low. However, I see the normal range for that particular lab goes down to even lower than 1.0, so given the excellent post-ACTH result and Liza's healthy behavior, I'm not going to worry about the pre-ACTH number. As always, if she were to start acting unwell, however, then you'd start wondering whether her cortisol is starting to drop too low.

Remind us, though, how long she had been taking the 40 mg. before this ACTH was performed?

Also, as far as the different Synacthen, I Googled several different labs and discovered that it seems as though the 1 mg. product can be used for ACTH testing in dogs, but it is administered as an injection into the muscle as opposed to via an I.V. drip. Here is a representative chart that I found, comparing the two forms of the Synacthen. I would definitely have your vet check with the manufacturer of the Synacthen, though, to make sure that this information is current and correct.

http://avc.upei.ca/files/avc/AVCDST_ACTHStimulationTestingProtocols_Canine-Feline.pdf

Marianne

[marinaliz]

Many thanks Marianne for the link!

The ACTH test was performed after 10-12 days since we increased the dosage to 40mg. Thanks god I listened to you and I didn't increase to 50-60mg, which my vet had suggested.

[molly muffin]

In Canada the vets and labs are now using Cortrosyn, same thing used in the states as the agent for doing the ACTH test.

Yay for good ACTH test!

[labblab]

OK, so after 10-12 days on the increased dosing, Liza's ACTH results dropped from the December results of:


Pre-ACTH: 1.6 ug/dL (44.4 nmol/L)

Post-ACTH: 6.2 ug/dL (172 nmol/L)

to:


Pre-ACTH: <1.0 ug/dL (<27 nmol/L)

Post-ACTH: 3.1 ug/dL (84.7 nmol/L)

The post-ACTH result for the most recent test is good, but since Liza dropped that far after only 10-12 days, there is a chance that she may drop even lower after a couple more weeks at the increased dose. Theoretically, she can still drop a little bit lower on the post-ACTH and still be within therapeutic range, but you don't want her dropping very much more at all, especially given the fact that her pre-ACTH is now quite low.

Since Dechra now makes a 5 mg. capsule, you could lower her dose to 35 mg. instead of remaining at the 40 mg., especially if she begins looking "off" to you in any way at all. That really might end up being the more desirable dose for her: halfway between the 30 and 40 mg. I just want to offer that thought for your consideration.

Marianne

[marinaliz]

Thank you both! I will talk with my vet about the option of Cortrosyn in case that Synachten (1mg) is not appropriate. In any case I bought it today (10 euros). I have read the instructions that Marianne sent me and I will also give them to my vet.

Marianne I agree with you, and actually that I was thinking of, that the right dosage for her might be the 35mg. However, I was told today by the pharmacist that in Greece the 5mg capsule is not available, ouf... Do you know if there is any other way to buy this product?

[molly muffin]

hmm, I don't know, other than maybe an online pharmacy that would ship to you with a prescription from your vet.

[marinaliz]

Hello! Today Liza took her 4th Vetoryl capsule since we have restarted treatment. No diarrheas so far but she looks very calm and slightly weak. I' m giving her 30mg/once daily, since I have not found yet the 5mg capsule. As far as I can remember she had almost the same behavior during the first days she had started treatment (almost before 3 months) the first time. After those days, she was reacting completely normal. Furthermore, her water intake has decreased considerably, something that I hadn't observed before three months where she was on the same dosage (30mg). I would like to ask if there is an adjustment period of some days after starting Vetoryl.

Thanking you in advance.

[molly muffin]

I don't think I would say an adjustment period so much as that you will notice a difference as the cortisol drops. Some dogs don't feel good for. Few days if there is a big drop.
Bit you don't want her to go to low so if she is lethargic, wobbly, not eating, drinking, gets diarrhea then you stop and test.

[marinaliz]

Ok, thanks Sharlene. I'm watching her closely. She asks for food and she has appetite. She does not vomit, and she does not have any diarrheas yet although I noticed that her stool was soft. I think that she is quite better today although not as good as she was the previous days.

[molly muffin]

If she has some soft stool a bit of probiotic or even a tiny bit of plain canned pumpkin might help with that

[marinaliz]

Could you please tell me if you agree with the following statement? I have found them in a paper which has been presented in a scientific conference (in 2006). Here is also the link:

http://www.ivis.org/proceedings/wsava/2006/lecture9/Reusch2.pdf?LA=1

1) …With regard to the LDDS test it has long been thought that all dogs with adrenal tumour (AT) show dexamethasone resistance (elevated cortisol concentration 4 and 8 hours after dexamethasone administration). However, it has now been described by us and others that a substantial percentage of dogs with AT may show suppression of cortisol 4 hours after dexamethasone which has originally been thought to be typical for PDH. Some dogs with AT even have normal cortisol concentrations after 4 and 8 hours. It is therefore advisable to perform additional tests with a higher sensitivity…

If the above statement is true, then I assume that the case of a dog which shows a cortisol measurement at 4 and/or 8 hours that is <50% of the baseline cortisol cannot be used as an indicator to securely differentiate between the pituitary and adrenal form.

On top of that I have read that in many dogs with AT the clinical signs of the disease are moderate, which was the case for Liza before the prezolon.

Having the above in my mind, I am wondering if the last radiologist missed something in the ultrasound. I would like to kindly remind you that he didn’t see any tumors in Liza’s adrenal glands while he also mentioned that both were enlarged (although not symmetrically). I am really wondering how is it possible the two masses which had been found in the previous ultrasound have now been disappeared. So, I am afraid if this radiologist missed something. I am wondering also if the fact that now both of her adrenal glands are enlarged could be attributed to Vetoryl treatment.

I would like to also mention that Liza has a mass on her spleen (approx. 14mm). I haven’t mentioned it before since I have been told from both radiologists that I shouldn’t be worry. So I thought that it was insignificant. The two ultrasounds have been performed with almost 3 months time interval between them and the mass has not changed at all. In fact, the second radiologist found the mass slightly smaller and he suggested me a new ultrasound after at least six months.

Based on all the above, as well as on the fact that she presented reductions in her general blood work levels (HCT, RBC etc.), I really worry and I’m afraid that maybe I miss something. I assume (and I hope!) that –at least– the second radiologist, in case he missed the tumors, would have seen if there was an invasion of her adrenal glands… To be clear, I’m thinking the case that the results of the LDDT were inaccurate for the differentiation, the second radiologist missed the tumors, the mass on her spleen is a metastasis (which could cause these reductions in her blood work levels).

I would greatly appreciate hearing your thoughts for the above.

[molly muffin]

Well was it a mass on the adrenals or a smaller nodule? Not all tumors are secreting also. Also, the question arises of whether the tumor on her spleen is causing some symptoms, as we have seen this before with a staff members pup.

I don't really know of anyway to know anything for sure, other than to have another ultrasound in the future and make sure they get clear pictures of the adrenals, spleen, liver, kidneys, pancreas, gallbladder with a full report.

Having had contradictory ultrasounds it makes it more difficult to know which is right and which isn't.

While normally it is true that you do not see suppression in a functional adrenal tumor on an LDDS, a nonfunctional or one that is not constantly putting out cortisol, you could see suppression. It is why in general, we like to see multiple tests to verify output. LDDS, ACTH, ultrasound are the top 3 tests when diagnosing cushings.

[marinaliz]

Do you mean that this nodule in her spleen maybe the culprit for the excess cortisol? The fact that only time will tell kills me… Unfortunately I cannot really understand the difference between a mass and a nodule. Below I post the results of the two ultrasounds. I will post only those for her adrenal glands and her spleen. For the other organs nothing significant is mentioned, except for her liver which was shown with increased dimensions (fatty liver) with no space-occupying lesions in both ultrasounds.

First ultrasound on 24/10/2015 (just a couple of days after the stroke. It was the 10th day of prezolon):

LEFT ADRENAL GLAND is shown with increased dimensions (length 33 mm, diameter of anterior pole 27 mm, diameter of posterior pole 10 mm). In the anterior and the posterior pole there are two hyperechogenic nodules with diameter of 24 mm and 6 mm, respectively.

RIGHT ADRENAL GLAND has normal position, shape, volume and echogenicity. The posterior pole is shown with reduced dimensions (diameter of posterior pole 4 mm and the length 25mm).

SPLEEN has normal position, shape and volume. Many multiple
hyperechogenic focal lesions are found which are compatible with myelolipomas while in the caudal part of the organ there is a hypoechoic nodule with diameter 15mm with a mixed structure.

(15/11/2015 We started Vetoryl)

(8/1/2016 We stopped Vetoryl)

Second ultrasound on 14/1/2016:

Both ADRENAL GLANDS are shown with increased dimensions of their posterior poles and mostly of their anterior poles (especially the left adrenal gland). Diameter of the left adrenal gland anterior pole 19,8mm. Diameter of the right adrenal gland anterior pole 13,1mm. Slightly heterogeneous parenchymal echogenicity. No space-occupying lesions identified in none of the adrenal glands. Conclusion: The findings are consistent with the pituitary form of Cushing’s disease.
(I would like to add to the above that I was there during the ultrasound and I show the imaging on the screen. I asked him if he sees any capsular or vascular invasion. He showed me that the capsule of both adrenal glands was intact and told me that capsular or vascular invasion is possible when there is a tumour, which eventually is not found in our case.)

SPLEEN has normal shape and volume. It has hyperechogenic focal lesions which are compatible with myelolipomas. A nodule is found of mixed echogenicity with dimensions 12,9x11,9mm.

[labblab]

Thanks for reminding us of that paper written by Dr. Claudia Reusch. Her comments about the equivocal LDDS results are especially interesting, because we have a new member with a dog who has been identified with an adrenal tumor on ultrasound, but whose LDDS results are instead consistent with pituitary Cushing's. So I am going to mention this article to her after I finish my reply to you.

I also am reminded that at the time this article was written in 2006, Dr. Reusch was advocating for the use of Lysodren instead of trilostane for the treatment of adrenal Cushing's when surgical removal is not an option. I'd be curious to know whether she still prefers Lysodren in this situation, because during this intevening decade, the general tide definitely seems to have turned towards treating ADH with trilo instead.

However, turning back to you and Liza...you are asking for thoughts, so here are mine. On the face of things, I would tend to accept the two radiologists' opinions regarding the nodule in the spleen. If it was indeed a primary malignancy or a metastasis, I would certainly have expected to see enlargement or other aggressive development over the span of three months. The fact that it appears to be even smaller than before would lead me to hope that it is indeed inconsequential, just as the radiologists have said, and unlikely to be either sinister or the cause of Liza's elevated cortisol and associated symptoms.

As far as trilostane enlarging the adrenal glands, yes, it does have this effect. So for dogs with pituitary Cushing's who do not have comparative diagnostic imaging, it is not possible to know exactly how enlarged the adrenals would have been beforehand, prior to the start of treatment.

If I am understanding your worries correctly, though, you are still especially wondering whether Liza may have a malignant adrenal tumor that has metastasized to the spleen? As stated above, the radiologists do not believe the splenic nodule is a worry, and I do not know of any reason right now not to accept their professional opinion. As far as the possibility of an adrenal tumor, I am going to ask you to take a big step backwards and look at the big picture.

You have already told us that Liza is not a surgical candidate, even if this should be the case. And yet, you are really torturing yourself over trying to rule "in" or "out" the possibility of an adrenal tumor. I must ask you, to what end? I deeply sympathize with your wish to learn as many answers as you can, but there comes a point where knowing some answers really would not make any difference in how you and Liza live each day together. As she nears the milestone of 15 years of age, even if none of these issues were at play, every day you are able to spend together is a gift and a blessing.

So this is what I would urge you to do. Before each new test, ask yourself whether the test result can/will actually change Liza's treatment in any significant way. If so, then by all means, the test can be valuable. But if not -- if the test result doesn't really change anything other than perhaps raise even more questions for you -- then I would think twice before proceeding right now. I would try to give Liza a break from the testing and yourself a break from the questions, and enjoy the time you are allowed to spend together each day.

Just my personal thoughts, coming from my own life of wasted worry :o :o :o. When I think back over all the hours of time that I have spent worrying over so many things -- many of which never even came to pass -- I wish so much that I could reclaim that time to use in other ways. So undoubtedly I am offering this advice just as much for myself as for you. But, regardless, these are my thoughts. ;)

Marianne

[marinaliz]

Marianne thanks... I'm crying at this moment... Thanks god I have found you, all of you. I really wish your life to be full of happiness every day because you deserve it.

I read the threat of the new member and that was the reason I searched more thoroughly on the internet for the interpretation of the LDDT results.

I know that she is old and obviously she is not a good candidate for adrenalectomy. However, even if she was, unfortunately, there isn’t any doctor that could make this surgery in Greece. I have searched it and I was told that even if she was a good candidate we should go to the Netherlands or somewhere else in Europe. You can see that we are far behind in our country, not only to animals care but in too many things… So, you are right that even if I learn if there is a tumor I can do nothing. But if this nodule in her spleen is a primary malignancy, I was thinking the splenectomy although that again I don’t know if she is a good candidate even for this. In any case, I know doctors that perform this kind of operation in our country. Obviously I am not in a position to question doctors’ opinion about her spleen but I was the one that observed these reductions in her blood work levels. Honestly I cannot hide my worries. I had in the past (almost 4 years ago) a personal experience with this organ and maybe that’s why I’ m thinking the worst scenario. At that time, everything started with abnormal values in blood work levels. Our adventure has ended after a couple of months and everything is fine now.

Now, I’m typing this she is seating next to me. I will try to have in mind that she looks very happy and healthy and acts completely normal. I wish you could see her right know how happy she looks.

[labblab]

Awww, I am picturing the two of you in my mind's eye, and it brings tears to my own eyes to think of you snuggled up together. :)

I believe I understand, only too well, how hard it is to set aside the worry. And I do think you are doing the right thing by continuing to monitor the blood counts and also the imaging. I guess I am just encouraging you to take at least a brief break, if that won't instead only make you worry about things more. I always feel as though the more I know, the less I will worry. Which is true, unless the things I find out about are truly worrisome and there are no easy answers. :o :o :o

[marinaliz]

Do you believe that a splenectomy (in case that the nodule is a primary malignancy) could it be a possible option? In about one week we will make another blood work. My instinct tells me that her levels will have been reduced more by then because nothing has changed. Vetoryl treatment is continued, her diet continues with strictly low protein foot, etc. So, the possibility to see her levels higher than the last time is too small, regardless if the blood results are attributed to her spleen or to secondary factors. And now I'm planning the next steps after I learn the new results. Possibly, an MRI could be the best option in order to obtain a clearer picture. Honestly I was hoping that I could avoid this (not for the money). In any case however, if an MRI is required, I will perform it. I know that I can do nothing for her adrenal glands but for her spleen maybe (and I hope) I can do.

[marinaliz]

Maybe an FNA under ultrasonological guidance could be an option but I know from my personal adventure that in humans the FNA of spleen is avoided and totally is not recommended because there is a possibility of diffusion of the cancer (if it is cancer).

[labblab]

I do not think a veterinary surgeon will consider removing Liza's spleen unless there is firm evidence of a pathological change, which is not currently the case. Two different radiologists have said that the splenic nodule is not a concern when viewed via ultrasound. Whether or not an MRI would be a better imaging tool in this situation, I do not know. It may or may not.

In addition to her age, another huge surgical risk factor for Liza is the possibility of her throwing another clot. I am doubtful that any surgeon would want to perform any invasive procedures unless there is clear reason to believe that the benefit would outweigh the risks of her throwing another clot to her brain or to her lungs.

Again, Liza's bloodwork thus far is still within normal range and at a level that I believe could be expected with Vetoryl treatment. Unless it drops significantly and abnormally low, I do not think there is cause for drastic intervention.

[marinaliz]

Thank you so much and sorry for bombarding you today with so many questions;)

[Joan2517]

Hi... I noticed that my Lena also got selective with food after starting the Vetoryl. What I did with her food was just put a little warm water in her kibble and then added a little bit of gourmet food for some extra flavor and she thinks she's getting something special. She also has an adrenal tumor that is inoperable. She is currently on 30mg once a day.

We are just beginning this journey as she was only diagnosed 12/11/15. I love this site. I don't cry as much and I feel hopeful for the first time since her diagnosis. You are not alone!

[molly muffin]

hmm, I don't see mass actually written anywhere. Nodule, which can occur on older dogs especially. My dog has one too, we monitor it with ultrasounds periodically, but the vet doesn't think it is secreting. Doesn't sound like they think that these are actually cancer tumors but rather "nodules" that grow. Almost like you'd think of a wart or lump that you get as you get older.
That seems to be what they think this is and if so, they are just there. I don't know if they are right or wrong and none of us do when we are told this kind of thing.

The blood clot factor makes surgery of any type would be a risk I'm guessing for Liza as I've been told that by my vets and specialist.

[labblab]

Yes, just stopping back in for a moment, I fear that the fact of Liza's ischemic stroke as recently as October really increases her risk of additional clotting issues. It really is a miracle that she has rebounded so well from her stroke. I am guessing the vets will be really cautious about challenging her further with biopsies or surgery. It is just the way it is -- the need to balance the risks and benefits.

[marinaliz]

I would like to thank you girls for your interest about Liza!!! She is having very good days and I can say now, after 3 months from the stroke, that yes, there has been a miracle, since she has COMPLETELY recovered. She is 99% her old self and I think that she acts again like she is 8 years old. She is playing, running and can do everything she could do before the stroke. The only thing that I don’t let her do is to climb stairs because very rarely she may lose her balance. Furthermore, Vetoryl seems that works fine for her with no adverse effects, so Cushing’s symptoms -at least for the moment- belong to the past! Today it is a really good day here with a lot of sunshine so we went for a very long walk and she was running like a pup. The only thing that has not changed is her appetite for food, but this is Liza!!! As far as I remember her, food is her life!

As for the possibility of another clot, I have it in my mind. I asked the vet if I should give her an aspirin or a substitute. He told me no, there is no need right now. Since her cholesterol and triglycerides are elevated, I was told to give her specific food so to reduce them. But, I have learned from the last time with the diarrheas episodes not to change food in the beginning of the treatment with Vetoryl. So, I will let some more days to pass and then I will add to her diet the specific food for reducing her cholesterol and triglycerides’ levels. Liza now eats only the renal diet food, which worked well for her kidneys. So, I intend in the coming days to start giving her a combination of renal diet with the specific food for her cholesterol.

Sharlene yes indeed, no one has mentioned me neither in written nor orally, the word mass. The word they used is nodules. As for the FNA, the first radiologist when he saw the nodule in her spleen he told me to go back after one month and make a new ultrasound. If the nodule had increased in size, then he would do an FNA. He also told me not to worry and probably it will be something insignificant. However, I never went for this ultrasound because I wouldn’t like to know what it was going on with the other nodules in her adrenal gland. In the meantime, after almost 3 months from the first ultrasound, I got the abnormal (false) values concerning her PLT count. So, before realizing that the elevated PLT count is false, I decided to do this ultrasound to see what was going on. But I was told to go to another radiologist which is considered one of the best. So, I did it. The first thing he told us when we entered the examining room and before the ultrasound was that indeed the nodules in her adrenals may have metastasized to her spleen and he would do also an x-ray of her chest after finishing with the ultrasound. Obviously I was panicked….Then he started the ultrasound and he started from her adrenal glands. He told me that there is nothing in none of her adrenal glands and the only thing he sees is enlargement. I asked him “what about the previous findings of the other radiologist?” and he answered that he knows what confused his colleague and he strongly disagrees. I didn’t ask anything else because I couldn't believe my ears. He seemed very confident. Then he moved to other organs and finally to her spleen. He saw the nodule and then he asked me to give him the findings of the other radiologist to compare. After a couple of minutes, he told me that the finding in her spleen is possibly nothing and I should not worry. I asked him if it is required to repeat the ultrasound after about one month and he answered that my dog is completely fine and if I like to make a new ultrasound this could be done AFTER SIX MONTHS OR EVEN NEVER… That’s the story…

Before concluding with this lengthy post, I would like also to welcome the new member Joan!!! Joan, as I can see our stories are similar to many points. I hope that Lena is doing better with her new dosage and I wish her new ACTH results to be good this time. I agree that we are very lucky that we have found this site!!! People here are wonderful! Although they all have their personal problems and their personal lives, they spend so much time everyday to inform us and to make us feel better. Personally, I owe them a lot. In my country we are far behind in animals’ care and through this site I have learned a lot. Finally, I would like to ask you if you know the reason that your vets believe that the tumor in her adrenal gland is inoperable. I think that this information would give the opportunity to the people here to obtain a clearer picture… Last but not least, please don’t feel so sad, I assure you that there will be better days once the best dosage for your Lena is found. We will go on this journey together and I hope to be quite long;)

[Joan2517]

Thank you so much for your kind words! When I was reading all your posts last night, I was thinking the same thing. I felt everything that you were feeling...

Her tumor is sitting over the right kidney and too close to the vena cava. My vet said that he was afraid one little nick and she would bleed to death and that would just kill me. She will be 15 March 19and I don't want to put her through something so traumatic.

I have been thinking of you and Liza all morning!

Joan

[marinaliz]

Do you know anything more about why they think that her tumor is inoperable?

[Joan2517]

It's sizeable, too close to the vena cava and her age.

[Trish]

Hi, my dog was a candidate for surgery and had adrenalectomy over 3 years ago now. But he was only 11 at the time and is a small breed with good life expectancy. His tumour invaded his vena cava but they managed to get that out just fine. I can understand both you electing not to proceed with surgery for your pups. But I do want to reassure you a little if I can. My dog was also noted to have a nodule on his opposite adrenal and one in his spleen. So over the last 3 years of repeat check ultrasounds neither of these adrenal or spleen nodules have grown significantly and we have not had to do anything invasive for Flynny, who is now nudging 15.

I think the specialists when they view ultrasounds can get a pretty good picture on what is a "nasty" nodule or not. I am sure glad we did not get Flynny's spleen taken out for that nodule when as it has turned out, was never going to bother him.

Hope that helps
Trish x

[marinaliz]

Thanks Trish! I hope the same is for Liza and Joan's dog... In fact, I wouldn't worry for this nodule in her spleen but some sudden reductions in her general blood work levels made me worry. In any case, she is doing great at the moment and she looks good. In a couple of days I will repeat the blood work and see if further reductions have take place. Many thanks that you shared your experience with me!

[marinaliz]

Hi, today, we made another blood test to see her levels in hematocrit. The previous test had been made on 16/01/2016. Unfortunately, we have another drop. Below I will post all the results from today's blood test.

This decrease in HCT really worries me, I can't believe that Vetoryl is the culprit for this huge reduction. Before almost one year her HCT was above 45. Before four months it was 41. Now it is close to 34. I cannot understand what is going on. There is nothing in her head (according to the MRI), there is nothing in her chest (according to radiographs). In her belly, according to the last radiologist, there is nothing to worry. Furthermore, she looks quite good and she has not lost her appetite.

[marinaliz]

13/02/2016:
HCT= 34,3% (37-55)
HGB= 11,3 (12-18)
MCHC= 32,9 (30-36,9)
WBC= 9,7 (6-16,9)
GRANS= 7,5 (3,3-12)
% GRANS= 77%
NEUT= 6,6 (2,8-10,5)
EOS= 0,9 (0,5-1,5)
L/M=2,2 (1,1-6,3)
%L/M= 23%
PLT= 671 (175-500)
Retics= 0,5%

ALB= 3,1 (2,2-3,9)
ALKP= 692 (23-212)
ALT= 66 (10-100)
AMYL= 1020 (500-1500)
BUN= 30 (7-27)
Ca= 11,1 (7,9-12)
CHOL= 272 (110-320)
CREA= 1,5 (0,5-1,8)
GLOB= 2,8 (2,5-4,5)
GLU= 76 (70-143)
PHOS= 5,7 (2,5-6,8)
TBIL= 0,6 (0-0,9)
TP= 5,9 (5,2-8,2)

16/1/2016:
HCT: 37,1% (37-55)
HGB: 12,5 g/dL (12-18)

12/1/2016:
HCT: 39,2% (37-55)
HGB: 12,5 g/dL (12-18)

21/10/2015 (just few days after the stroke and before starting Vetoryl):
HCT= 41% (37,1-57,0)
HGB= 13,9 (12,9-18,4)

22/01/2015:
HCT= 45,3% (37,0-55,0%)
HGB= 15,2 (12-18)

[marinaliz]

I am afraid that I miss something, I don't know really. My vets don't worry but I am thinking, when will they worry?? If the HCT drops to 25?? I just called the last radiologist to arrange another ultrasound for this Tuesday. I want to check again her adrenal glands and her spleen. Really, I can't think anything else, except of her spleen (or a wrong diagnosis for her left adrenal gland that it has no tumors) that could cause these abnormalities in her blood test. Do you have any thoughts? I really trust your instinct and your knowledge. I have lost my mind again...

[molly muffin]

Have they done a blood smear to check for reticulocytes? To see if new blood cells are being made in response to the low blood cell HCT count.

[marinaliz]

No Sharlene, they have not done this test. I will ask for it. Thanks a lot.

I am very disappointed and I feel so lonely. I feel that my vets don't give the attention that is required and attribute these abnormalities to the medication. Furthermore, I believe that they are thinking her age and they leave her to her fate. Unfortunately, I was the one that discovered these reductions and I was the one that ordered these consecutive blood tests. And I am not a vet. I have paid too much money during the last four months and unfortunately I think that Ι am receiving consecutive misdiagnoses. I wish we lived in another country, and believe me, I have many reasons to say this. I am so tired and disappointed… I am really wondering if she was an 80 year old human, if she would have the same approach. The only thing that gives me strength right now to continue searching what is going on with her is that she still seems healthy and happy. I can’t let her. I have scheduled for tomorrow another ultrasound and I will ask to see also her heart for possible metastasis.

I have made all these days my own research through the internet and I have read numerous scientific articles. Unfortunately, I believe that the last diagnosis I have gotten from the last radiologist for her adrenal glands is wrong. I believe that both of her adrenals glands are now enlarged due to Vetoryl and eventually she has the adrenal-based form and she likely belongs to the bad 50% which is cancerous. As far as for the “disappeared” nodules, I don’t now what to say. Maybe the prezolon had caused these abnormalities. Moreover, the radiologist writes in his report that there is slightly heterogeneous parenchymal echogenicity but I have read that in the pituitary-form of the disease the echogenicity of the adrenal glands is homogeneous.

On the other hand, I am really wondering how difficult it is a “mass effect” to be detected. If it is indeed difficult, it is very likely that the last radiologist gave me wrong diagnosis. In any case however, the worst scenario seems to me that it could now be possible, and the nodule in her spleen is a metastasis. Unfortunately this scenario has not solution. On the other hand, if indeed it is not a metastasis from her adrenal glands then it may be a primary cancer. In this case splenectomy is the only solution but again it is written that it has poor prognosis since the tumours found in the spleen have already spread to other organs (lungs, heart, etc.) the time they are discovered. The spread may not be obvious in ultrasounds and x-rays but after two-three months can usually be detected. Furthermore, it is written that most of the masses found in the spleen are malignant (2/3), from which more that 50% are hemangiosarcomas. And guess what! It is quite usual for the dog not to have clinical signs. The only sign that may be present is anaemia, which may be mild, as well as thrombocytopenia. Obviously, in our case thrombocytopenia does not exist due to Cushing’s. Oh god, I feel so lonely and helpless.

[marinaliz]

Vets here tell me that they are not worry. And I’m wondering when they will begin to worry. When she collapses?? Or when her HCT drops to 20?? Oh my god… If you think that there is something else I could do to clear up the situation, please tell me… I am prepared to make whatever is required to save my dog. She looks quite good, I can’t let her.

All these days I was giving her 30mg once daily. But I noticed that her increased water consumption was returning. According to the last ACTH results it seemed that the appropriate dosage for her would be the 35mg. But guess what! In our country the 5mg capsule has not been approved yet and I cannot buy it from anywhere. So, from yesterday I have increased her dosage from 30 to 40mg. At this point I should also mention that hemangiosarcomas can be related with increased water consumption and urination.

[labblab]

I am really sorry that Liza's HCT and HGB continue to drop, and I do understand why this is so worrisome to you. One thought occurs to me re: relative easy testing -- are you sure she's not losing any blood through her GI tract and passing it into her stool? I'm assuming this would be as easy to check for in dogs as it is in humans.

Marianne

[marinaliz]

Thanks Marianne. Her stool are totally clear, at least macroscopically. I haven't done any test for that but I am afraid that it isn't from there the drop.

[marinaliz]

Hello! Just came back from the radiologist. We made an abdominal ultrasound, an ultrasound scan of her heart and 3 new x-rays.

The heart is normal and the results from the x-rays are normal too. The size of the left adrenal gland as well as the size of the nodule in her spleen remained almost unchanged compared with the previous ultrasound.

The radiologist said about the nodule in her spleen that it is impossible to be related with the decreased HCT levels. Its size is too small (tiny) and it is the same as it was before 4 months. If it was cancer he would expect to see an obvious enlargement of the nodule or other aggressive development after 4 months. So, he suggested me to forget it and there is no need to recheck it for at least for 6 months.

Concerning her adrenal glands he to told the same things he had told me before 1 month. Nothing has changed in his diagnosis. He believes that Liza has the pituitary form although the size of the left adrenal gland may be relatively large (with almost 2cm diameter). I insisted if he sees any “mass effect” and he answered in no way. He also said that if it was a “mass effect” the echogenicity as well as some other ultrasonographic characteristics would be different.

Finally, concerning the reduced HCT levels he told me that the dog has not any signs of cancer in any part of her body so I must seek with my regular vet for other reasons which can cause these reductions (e.g. Vetoryl, diet, etc.).

[marinaliz]

Now I am going to ask my regular vet to do the test for reticulocytes and after that I don't know... The good thing is that nothing is found according to the radiologist. We will see...

[labblab]

Well, that is certainly good news about the ultrasound!! :) :)

You are feeding Liza a very protein-restricted diet, is that correct? Did this dietary change correspond to the same time that her red blood counts starting dropping?

I believe you started the protein restriction due to her temporarily elevated kidney values? But perhaps the severe restriction is no longer necessary, if the kidney issues were only the temporary result of an acute issue (wasn't it vomiting and dehydration?).

[molly muffin]

That is one of the things that is recommended actually for low HCT, is to increse protein, even feed liver to get them back up. Not too much but too much of a protein restriction can be just as dire as over giving them protein, so diet and checking the smear is probably the things I would do.

[marinaliz]

Well, Liza’s HCT before one year was around 45-47%.

4 months ago (just after the stroke) the HCT was 41% and the HGB 13,9 (21/10/2015).

3 months ago we started Vetoryl (15/11/2015). After one week from starting treatment she had some diarrheas episodes and her creatinine levels increased significantly (from 0,9 to 2,9).

I started feeding her strictly with Purina ProPlan Renal Function on 02/12/2015.

On 22/12/2015 her HCT was 39,1% and the HGB 13,7 (almost the same level with that of 21/10/2015).

Now she has HCT 34,3% and HGB 11,3. Her creatinine is 1.5 (not too high but not low).

Based on the above, her HCT decreased from 41% to 34% within 4 months and indeed the biggest noticed drop started (from 22/12/2012) with the change I made in her diet while she was also taking Vetoryl. However, it’s hard to believe that the food can cause this reduction. Maybe in combination with the drug…I don’t know. I really want to believe this scenario… and really she seems healthy. She does not seem sick.

[labblab]

I just looked at the profile for the Pro Plan Kidney Function food sold here in the U.S. and it appears to be severely protein-restricted -- the dry food is only 12% protein, and I don't even see a recognizable protein source in the dry ingredients other than maybe egg product. My understanding is that such severe protein restriction is neither necessary nor healthy for a dog whose creatinine and BUN are within normal range. You only want to restrict protein that severely if kidney function is so abnormal that it cannot properly process the protein waste products (the dog is "azotemic"). Dogs who are spilling significant amounts of protein in their urine may also benefit from moderate protein restriction. I cannot remember whether Liza suffers from any degree of proteinuria. But regardless, with her return to normal creatinine, I would give her food with more and better-quality protein. I'll bet that might improve her blood counts!

[marinaliz]

Yes, this is the dry food I am giving her. I will try to alternate her food in the day between the Purina ProPlan Renal Function and the Hills r/d (weight reduction, 34,5% protein) and see how she goes.

As for the nodule in her spleen I will take it out of my mind since it is indeed tiny and it is highly unlikely causing her any problems. On the other hand, the large size of her left adrenal gland has stuck in my mind…I would like to ask you based on your experience if it is possible a “mass effect” on an adrenal gland not to be seen by a radiologist in two consecutive ultrasounds. He insists that the adrenal gland is clear. In other organs, such as the spleen or lungs a mass effect is easily detectable and I’m wondering if it is the same for the adrenal glands.

I know what Marianne maybe thinking right now:) Since I cannot do anything with her adrenal glands why I’m still thinking about that… The reason is that if the radiologist has made a wrong diagnosis and an adrenal mass is there, I’ m wondering if this mass could have caused this reduction in blood counts.

[marinaliz]

In other words, what I'm trying to say is: a mass effect is assumed based only on the size of the adrenal gland or there must be also some other ultrasonographic characteristics in order to lead a radiologist to make the definite diagnosis for adrenal-based Cushing's.

[labblab]

Hello again! Unfortunately, I am not an expert on ultrasound imaging or interpretation. My impression, though, is that adrenal tumors seen on ultrasound appear as identifiable masses. Size is a factor, in that the affected gland will be enlarged or distorted due to the abnormal cell growth, but I think the tumor itself will generally be visualized in some way. Also, in the presence of a functional adrenal tumor, the other gland will appear to be atrophied. But I am basing these comments solely on what people have described here over the years.

I truly am much more suspicious of Liza's food, especially since her blood count drop began and has proceeded since you made the feeding change. I've just now looked at the Hill's r/d weight reduction food, and as is the case with most weight management foods, the leading ingredients are grain. Even though the analysis shows a protein percentage of 34%, it looks to me as though the main protein sources are chicken by-products and soy. Here are the leading ingredients:


Whole Grain Corn, Corn Gluten Meal, Chicken By-Product Meal, Powdered Cellulose, Soybean Meal, Soybean Mill Run, Chicken Liver Flavor, Dried Beet Pulp, Pork Liver Flavor, Soybean Oil, Lactic Acid, Caramel color, Pork fat, etc.


Here are the leading ingredients in the Pro Plan food:


Whole grain corn, brewers rice, dried egg product, animal fat preserved with mixed-tocopherols (form of Vitamin E), sugar, dried whey, sodium caseinate, animal digest, calcium carbonate, vegetable oil, etc.

So even in combination, it seems to me that Liza is eating absolutely no quality protein whatsoever. Prescription foods do have their place, but seemingly they are best used on a temporary basis to address a specific acute need. If I were you, I would be avoiding specialized food at the moment, and instead feeding Liza a quality commercial food that contains a moderate amount of recognizable animal protein as a leading ingredient. I have no nutritional training, but all I'm seeing Liza eating right now is a whole lot of corn, corn, corn! :eek: :eek: :eek:

I have no idea whether changing her food will help her blood counts, but this is the very first thing I'd try after seeing the profile of the food she's been eating since her blood counts started dropping.

[marinaliz]

Thanks Marianne for the advice! Ι will try for some days a quality commercial food that contains a moderate amount of recognizable animal protein as a leading ingredient and see how she goes with her HCT and creatinine. Maybe I'll try a combination of the Purina with the new dry food...

By the way I'm laughing right now with the corn, corn, corn!!! To be honest, I hadn't noticed the ingredients in detail...

[marinaliz]

I just called the radiologist to ask him some things that I didn't ask yesterday but he was examining another dog...ouf. He will call me back later in the day.

I believe that he thinks I'm totally crazy with the some many questions I make...

[marinaliz]

Hello! I just learned the results from today’s blood test, and yes! You were right! One more time I want to thank you so much …

Liza had today a blood test to check her HCT levels. In the previous test (before 17 days) her HCT was 34,3% (r.r. 37,00-55,00). Today’s result for HCT is 38,2%. I’m not giving her only the renal diet food (as you suggested), which is severely protein-restricted, but I started to use (not every day, two to three times per week) a combination of the renal diet with some homemade food (e.g. beef liver). To be honest, I was very afraid for today’s results but things are not as bad as I was expected. The change in her diet worked and most importantly her HCT and HGB didn’t go even lower. By the way, her reticulocyte count is also within the reference range!

We made also an ACTH test to check her levels in case there is a need for a dosage adjustment. Hopefully, tomorrow I will be informed the results. I have noticed a small increase in her water consumption. Otherwise she is doing great. She seems happy and healthy:)

[Harley PoMMom]

Glad to hear that the diet change worked and that her numbers responded so well!!

Yep, when you get those ACTH stim test results please do post them here...thanks!

Hugs, Lori

[molly muffin]

Yay that is great news!

So glad to hear that the blood values are have not only not gone lower but are also a bit better. Good news indeed, let us know what the ACTH shows.

[labblab]

Oh, I agree -- this is excellent news! :)

Given this initial response to the diet change, though, I have to tell you that I would now start transitioning Liza off the highly restricted renal food entirely. It has the profile of a food that you would give to a dog who is actively experiencing renal failure. As long as Liza's creatinine and blood urea (BUN) are within normal limits, I don't think she needs to be eating that food at all and it looks as though it may actually be harming her. So I wouldn't just supplement that food, I would stop feeding it altogether and switch to a good quality, moderate protein food that has more nutritional ingredients all on its own.

Again, I am no nutritional expert, but that's my personal thought about all this. ;)

Marianne

[marinaliz]

Thank you all for your responses. I’m here again with the results of the ACTH test. I’ll post also the results of the previous tests.

15 November 2015 she started taking Vetoryl (30mg once daily).

16 December 2015
Pre-ACTH: 1.6 ug/dL
Post-ACTH: 6.2 ug/dL

Since the clinical signs were still present, on 29 December 2015 we increased the dosage to 40mg once daily.

10 January 2016
Pre-ACTH: <1.0 ug/dL
Post-ACTH: 3.1 ug/dL

Although she responded well to the new dosage (40mg), on 11 January 2016 we stopped Vetoryl due to the HCT level reduction.

On 22 January 2016 we started again treatment with Vetoryl by giving her 30mg once daily.

On 14 February 2016 we increased the dosage to 40mg because some of the clinical signs were still present.

The new results are:
29 February 2016
Pre-ACTH: 5.1 ug/dL
Post-ACTH: 7.9 ug/dL

I would like to mention that this last test was performed 6 hours after her dosage, while the two previous tests were done 4 hours after her dosage. Furthermore, I would like to mention that her blood sample was not sent abroad this time for evaluation, as it was done in the two previous tests. The reason is that I have found a new vet that has plenty of the ACTH agent to perform the required tests who evaluates by himself the blood samples and does not send them to a specialized lab for evaluation. I would like to kindly remind you that in the city I live the agent is completely unavailable. So, I felt quite lucky finding this new vet. However, I would appreciate hearing your opinion on the following four points:

1) According to the new results, there is a need for a dosage adjustment. Liza now takes 40mg once daily. The new vet suggested giving her 30mg in the morning and 30mg in the afternoon (in total 60mg). However, this sounds quite strange to me as I cannot understand how the double dosage will decrease her post ACTH levels. In other words, now with 40mg, she has 7,9 ug/dL. If I decrease to 30mg in the morning and perform an ACTH test after 4-6 hours, this ACTH level won’t increase even more? So, I was thinking the 50mg in the morning being more appropriate and maybe adding another 10mg in the afternoon (the 5mg capsule is unavailable in our country).
2) Another strange thing to me is that before almost 1,5 month she had a post level of 3.1 ug/dL and now on the same dosage (40mg) she has 7.9 ug/dL. I have read some other member posts where it is written that in dog’s with adrenal-based Cushing’s it is very difficult to find the appropriate dosage and there is a need for frequent dosage adjustments because the disease develops and progresses quite quickly in comparison to pituitary-based. Could it be a reasonable explanation of the increased levels in her last ACTH test?
3) I was wondering if the increase in her HCT level from yesterday’s blood test could be a result of the increased (natural) cortisol (people who suffer from anaemia maybe given steroids).
4) Lastly, the new vet said something quite strange, which I think that is totally incorrect but really I would like hearing your opinion: He suggested to give her for 15 days 30mg in the morning and 30mg in the evening and then to continue treatment with only one or two pills PER WEEK…!!! How is it sounds??

[molly muffin]

I understand that it is exciting to find a vet who has the ACTH agent available. However, I have to say based on his responses, he has very little actual knowledge of the drug he is using.

If she did good on 40 and I think that after only two weeks she would have dropped even further she was on 10 January, 30mg should have been a good choice. But if you wanted to try 40mg again, you would split, not double the dose for morning and evening. I think at 60mg you'll definitely end up in trouble. You could do 20 am and 12 hours later 20mg or you could try 20mg in the morning and 10mg in the evening.

His idea of doing 30mg for awhile and then going to twice a week, is something you might do with lysodren, but would be worthless with trilostane, they work in completely different ways. Not sure he understands that.

I am inclined to think the HCT is more a direct result of the dietary changes you have made than the vetroyl.

Lets try printing out the information from the manufacturer of the drug and giving that to your vet, so maybe he can learn how this drug works and the proper protocols.

While you would expect the level to be higher at 6 hours than 4 hours I'm not sure how much higher it would be.

Here is a link to the manufacture information:

http://www.dechra.us/Admin/Public/Download.aspx?file=Files%2FFiles%2FSupportMaterial Downloads%2Fus%2FUS-046-TEC.pdf

[labblab]

Although she responded well to the new dosage (40mg), on 11 January 2016 we stopped Vetoryl due to the HCT level reduction.

On 22 January 2016 we started again treatment with Vetoryl by giving her 30mg once daily.

On 14 January 2016 we increased the dosage to 40mg because some of the clinical signs were still present.

The new results are:
29 February 2016
Pre-ACTH: 5.1 ug/dL
Post-ACTH: 7.9 ug/dL
I first want to clarify what I believe is an error in what you wrote above. I think Liza restarted the 40 mg. on February 14 and not January 14, correct? If so, that means she was taking the 40 mg. for only two weeks prior to this testing. Also, as you do say, this time she was tested 6 hours after dosing instead of 4 hours. So first and foremost, especially since you've told us that Liza's behavior is generally good right now except for perhaps a bit more thirst, I would not yet change the dosing at all. I would give Liza at least a full month at the 40 mg. dose and then recheck her cortisol level again -- and again at the 6 hour mark if that is to be the timeframe from now on. Liza's higher test this time may indeed be due partly to a possibility that the effect of the trilostane was already starting to wear off at the later time of day. Also, the fact that the test was analyzed by two different labs/vets may also have introduced some variability. If you are still noticing an increase in thirst/urination at the 30-day mark and her post-ACTH result is still higher than 5.4, then yes, I think you could consider a small dosage increase. But as Sharlene says, I would not increase up to 60 mg. daily total -- perhaps instead to 50 mg.

As for twice daily dosing and ACTH test results, it may seem odd to you, but dogs who are dosed with half the amount twice daily may actually have a lower post-ACTH result 4-6 hours after the morning dose than do dogs who are dosed with the same total given only once each day. My understanding is that when trilostane is given every twelve hours (even only half the total), cortisol levels never rebound as highly at any time of the day. Therefore, cortisol never needs to be "dropped" as severely at any time of the day, either. It stays at a more consistent plateau throughout the 24 hours, rather than having the opportunity to rise more markedly after the drug's effect has worn off during the evening and overnight. Thus, twice daily dosing can also solve late-day symptom rebound for dogs whose cortisol levels start rising too quickly too soon after a single morning dose.

So as Sharlene said above, if it suits your schedule and especially if you notice Liza's thirst worsening later in the day, you could first shift to giving her 20 mg. both morning and evening, along with a meal (or 30 mg. in the morning and 10 mg. in the evening). See if that helps her symptoms and also how the next ACTH turns out in a couple of weeks (still testing at the same time of day). Either way, however (40 mg. in the morning, or 20 mg. twice daily, or 30 mg. in the morning and 10 mg. at night), I wouldn't yet increase her daily total at this time. I would wait to reevaluate after a retest at the 30-day mark at 40 mg. in some form.

As far as the vet's suggestion to increase to 30 mg. twice daily and then shifting to dosing only a couple of times a week, that makes absolutely no sense to me, either. I am hoping maybe there was some misunderstanding as to what was meant by that.

Marianne

[marinaliz]

ok, many thanks to both of you. Marianne you are right, I made a typographic error in my last post. The (re)starting day of the 40mg was February 14. I have corrected it now in my previous post.

The difference between single vs double daily dosing makes sense to me now. I thought that the twice daily dosing was appropriate only for dogs who exhibit late-day system rebound, which is not the case for Liza. I’m not seeing any difference in her behaviour between the morning and later in the day. Now, I have understood the difference. Indeed, I have noticed a small increase in her water consumption during the last days. Before, she was drinking approx. 55-60ml/kg and now she drinks 70-80ml/kg. So, starting from tomorrow, I’ll give her 30 mg. in the morning and 10 mg. in the evening and see how she goes. I’ll make another ACTH after approx. 15 days at the 6th hour mark.

Unfortunately, there was not a misunderstanding. The new vet suggested dosing only a couple of times a week, meaning that his knowledge for the drug is limited. However, I have no other options right now since he is the only one that has the agent. I’m going to kindly explain him the difference, based also on Dechra’s leaflet, hoping that he will understand and will not become angry with me. He seems a really good person.

[molly muffin]

Sometimes you don't get the vet that has all the knowledge and that can be okay as long as you get one that will work with you and is willing to learn right along side of you. :)

[labblab]

You and Liza popped into my mind yesterday, and I'm just wondering how you've been doing this spring. We'd love to read an update anytime you might want to stop back by once again!

Marianne

[marinaliz]

After a quite long time I’m back again! Thanks Marianne for your interest!! I hope you are doing great!

To be honest, I wanted to take a break from everything related to Liza and her Cushing thing and remove all the bad thoughts that I had in my mind after her stroke and her Cushing’s diagnosis. Eventually I think that I did the right thing. Liza seems very healthy, she has completely recovered from the stroke (100%), she is running, jumping etc. She seems energetic and active, like an 8-year old dog (although she is now 15!). Her appetite is good and she drinks (finally!!) normal water quantities. She is now taking (for almost 3,5 months) 60mg split into two doses (30mg in the morning and 30mg in the evening).

My vet suggested me to take a break from the numerous and continuous blood tests related mainly with her HCT levels etc. He believed that there wasn’t something that I should worry and now I thing that he was right. She hasn’t made any blood test for almost 4 months. Next week I’m planning to get her to the vet for the ACTH test, although, to be honest, I would prefer to avoid it in case that something weird comes up and start to worry again... In any case, I am so happy that she looks so healthy and I try to spend as much time as I can with her!!!

My best wishes and thoughts to all of you :) 

[Joan2517]

Good news!

[labblab]

Oh, thank you so much for this update!!! :) :)

I'm so glad you two have had a break from all the testing and worry, and I surely hope the ACTH test next week will go smoothly.

It is so good to hear from you, and I send both you and Liza all my best wishes. ;)

Marianne

[marinaliz]

I' m back again with Liza's new blood test results. Unfortunately, my vet ran out of the ACTH agent so we couldn't perform the ACTH test to check her cortisol levels...

The values that were above the reference ranges are:

PLT 811 (175-500) (it does not worry me since it is usual for Liza)
ALP 755 (23-212) (it does not worry me since it is usual for Liza)
GLOB 4.8 (2.5-4.5)
TP 8.4 (5.2-8.2)
Ca 13.6 (7.9-12.0)
CREA 2.6 (0.5-1.8)

Everything else was within the normal range. The last two values seem extremely worrying, especially that of blood calcium. I know that the No1 cause for calcium elevation is cancer. All of my fears came back and I feel terrible… Please, can you tell me if you know that something else may be the culprit for calcium elevation? I’m reading on Google that maybe a low cortisol (due to an increased Vetoryl dosage) could increase blood calcium. Is that true?

Obviously, I will feed Liza only with the renal diet. I should mention that she looks very healthy, and to be honest I haven’t seen her in such a good condition for months.

Please help me, I need your advice :(


[marinaliz]

I would like to add to the above that her HCT and all the other values in her general blood work were within the normal range.

Unfortunately, I see that in her biochemical blood analysis my vet did not include electrolytes (sodium, potassium).

[Harley PoMMom]

Besides cancer there definitely can be other reasons for elevated calcium levels, a parathyroid disorder is one, and when calcium levels are increased than an ionized calcium test is recommended and perhaps having the parathyroid gland checked too.

The increased creatinine level is a bit more worrisome to me since this has been elevated in the past. There is a new test for kidney function which is the SDMA (Symmetric dimethylarginine), and if this were me I would have that test performed, here's a link to literature about the SDMA test: https://www.idexx.com/small-animal-health/solutions/articles/sdma-diagnose-kidney-disease.html and https://www.idexx.com/files/small-animal-health/solutions/articles/sdma-faqs.pdf

I certainly understand your worry and please remember we are here for you and Liza.

Hugs, Lori

[marinaliz]

Thanks Lori! My vet mentioned the parathyroid disorder too. He does not worry. But was is that? Is that something that can increase so suddenly? Before four months her blood calcium was 11,9 and before four years it was again 11,9 (always at the upper level!).

We will repeat the blood test in two weeks.

As for her creatinine, I agree that is worrisome. On the other hand, both phosphorus and BUN are within normal range. I hope feeding her again only with the renal diet may lower a bit her creatinine. I'm thinking seriously to reduce a bit her daily Vetoryl dosage (e.g. from 60mg to 50mg). This drug has contributed significantly to the increase of her creatinine.

Do you know what will be the next step in case that her creatinine remains such high? Is there anything that I can do to help her except the renal diet? My vet says that there isn’t, however he believes that the new food is going to have positive results, at least for some time…

[Harley PoMMom]

This web site has a good explanation of the parathyroid glands:
Parathyroid glands control the calcium in our bodies--how much calcium is in our bones, and how much calcium is in our blood.http://www.parathyroid.com/parathyroid.htm

Increases in the creatinine may be transient but unfortunately, when dealing with kidney disease, when the creatinine level increases there is usually a 50%-75% loss of kidney function, this is the main reason I would want to have that SDMA test done, just to see if that increased level in the creatinine is due to a kidney issue.

When a dog does have renal disease there are many things one can do to help slow down the injury to the kidneys. A kidney friendly diet is important, giving fish oil because of its anti inflammatory properties, making sure the dog is well hydrated, and the supplement CoQ10 may help decrease the creatinine, also you want the BP checked often because high BP does damage to the kidneys, there are also medication, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers, that are used to help curb the assault on the kidneys.

Hugs, Lori

[marinaliz]

Ok, many thanks Lori! I'm going to search about the supplement CoQ10 and the fish oil. Unfortunately, none of my vets has recommended any of those... I will make search on my own. I don't know if there is a specific brand for these (and which is the best), and if they are available in my country. I will ask my pharmacist if we can find any of these supplements. If you know a specific worldwide delivery brand name, it would help me a lot.

As for the medication, I will discuss it with my vet, hoping to find the appropriate for Liza. I don’t know which from the two is the most appropriate for her case. However, I remember last week that I asked him if there is any medication for kidney failure and he answered that there isn’t… I’m going to ask him again.

I searched about the elevated calcium and except of the parathyroid disorder I found that a chronic kidney disease can cause alternations in calcium (it may increase, decrease or remain normal). So, I’m thinking that this could be a reasonable explanation of her latest abnormal blood test results concerning calcium. Liza has (mild) problems with her kidneys since 2012 and unfortunately, with Vetoryl these problems got worse. In 2012 she had an episode where her creatinine reached 2! At that time the ultrasound revealed a probable congenital abnormality of her kidneys. Since then her creatinine remained close to 1 up to the day we started Vetoryl where it started rising again.

[Harley PoMMom]

Vetoryl can unmask a kidney issue which it did with my boy, Harley. Just to clarify, Vetoryl did not cause the kidney issue and looking back on Harley's ultrasounds there were abnormalities that were shown with his kidneys.

Regarding the supplements, I used wild salmon oil and CoQ10 which I purchased from Monica Segal http://www.monicasegal.com/Wild_Salmon_Oil.html I know you can buy fish oil online, you just want to make sure that the fish is not farm raised it's the wild fish you want. And the CoQ10: http://www.monicasegal.com/Wild_Salmon_Oil.html

Unfortunately chronic kidney failure is not reversible, one can only help slow down the damage to the kidneys.

Hugs, Lori

[molly muffin]

I'll just add that my dog has at various times shown to have elevated calcium levels, and we'd start talking about parathyroid testing and then the next test it would be normal. We've bounced on that dratted calcium level any number of times and finally have decided that this is just my dogs normal these days.

[marinaliz]

Thanks Sharlene. Thanks to all of you for your valuable support.

I'm again very worried about my girl due to the elevated calcium, although my vet told me that I shouldn't and maybe a parathyroid problem is the culprit. He told me that if the calcium continues to be high we will proceed to the parathyroid testing on September (I’m just wondering, isn’t too late on September??). On the other hand, I'm reading everywhere on the Internet that the elevated calcium is a "red flag" and almost all the times it is due to a tumor somewhere. But Liza doesn’t seem ill, exactly the opposite, she seems healthy. I don’t know. I am again so confused… All the bad thoughts I had in the past have returned. The possibility that her Cushing’s is due to an adrenal tumor, crosses again my mind. And if this is true, can a cancerous adrenal tumor elevate the calcium? Or, if it has metastasized to her kidney and that is the reason that she has both elevated creatinine and calcium? Or, I have gone completely crazy as I did in the past with her HCT levels!

Can I ask you -if you know- if the parathyroid disorder occurs so suddenly? Before almost 4 months her calcium was 11,9 and now it is 13,6. What was the highest noticed calcium level of your dog? The 13,6 isn’t too high? Furthermore, is it true that low cortisol can contribute to calcium elevation? I don’t say that Liza has Addison’s but during the last 3-4 months we have increased the dosage of Vetoryl from 40 to 60mg (daily) without performing an ACTH test (we cannot find the ACTH agent). Furthermore, I’m reading that kidney disease can cause calcium elevations, although this possibility is quite small. The other two increases that she had in her Globulin and Total Protein what do they mean? (GLOB 4.8 (2.5-4.5) TP 8.4 (5.2-8.2))

I'm sorry for asking so many questions but I need help with this please…

[marinaliz]

Hello! It has been a long time since I last wrote to you…hope all of you are doing well!

Liza is doing quite well and she is still on Vetoryl (it has been one year since she first started the drug). Her current dosage is 70mg daily (i.e. 40mg in the morning and 30mg in the evening). She weighs 12kg. She is on that dosage more than 6 months. I just received her last ACTH testing results:

Pre: 29.2 nmol/L
Post: 72.8 nmol/L

My vet believes that her results are close to the lower level and she suggests reducing the dosage to 60mg (i.e. 30mg in the morning and 30mg in the evening). Could you please advise on this?

All other blood test results are in the normal range or close to the normal range. However, we still keep an eye to her creatinine level which is slightly elevated.

My best wishes and thoughts to all of you ;) 

[Harley PoMMom]

For our members here in the states that are used to seeing ug/dl units I am converting Liza's ACTH stim results ;): Pre: 29.2 nmol/L = 1.05 ug/dl and Post: 72.8 nmol/L = 2.64 ug/dl.

I definitely wouldn't want her numbers to go any lower, and on the forum we have seen where a dog's cortisol level drop when their dosage remained unchanged, so if this were me, I would opt to decrease her dosage to the 30 mg BID.

It is so wonderful to hear that Liza is doing so well!!!

Hugs, Lori