Newly Diagnosed, Worried about Treatment Effects (Chio)

[ChiosMom]

Hello everyone!

I have been busy reading tons of new and old threads on this forum since I recently came across it, and would love some insight, help, and guidance from the Cushings experts here. Be forewarned....I am a bit of a hypochondriac about the health of my pup Chio as he truly is my everything. He has been at my side for the last eleven years though lots of ups and downs (including the loss of my father), and I am here to be as diligent as I can about his wellbeing.

My main concerns are the side effects of his Vetoryl, as reading the insert with his meds really put the fear of heaven and hell into me. Also if anyone could give some guidance on his recent blood, urine, and ACHT test results (below) I have some concerns with them too. I am not here to undermine my vet, but as I have had vets misguide me in the past I need to do my due diligence for the best outcome of my dog.

Timeline: My vet and I have been suspicious of Cushings for the last ~year or so. Chio is ~13 years old (was a rescue so estimate on age), Chihuahua, 14 pounds, and about a year ago with his annual urine test we noticed high protein levels. At that time besides having a bit of a chubby belly and them physically feeling he had an enlarged liver they decided to try some meds and a new renal support diet to keep the proteins down to protect his kidneys in his advancing age. Fast forward to ~5 months ago I noticed him having more dribbling accidents (leaking a few drops of urine, usually at rest) and noticed some increased thirst. Late last year my vet more-so suspected Cushings due to the events of the past year so we did an ultrasound that showed his liver was indeed enlarged, adrenal glands enlarged but no sigh of tumor(s) or shape irregularity, and all else looked fine. Suspected pituitary Cushings vs. Adrenal tumor, we did a ACHT test on January 12th 2020 which came back as a negative for Cushings. My vet was very surprised but we know of false readings. No medication was prescribed at that time. Fast forward again to March 26th 2020 I took him in for his senior panel and urine check up and we see his liver enzymes are off that charts which was very scary for me (protein levels in urine better than previous tests). A couple days later we did another ACHT test to which he was confirmed Cushings so we are now on day five of Vetoryl.

He is also on Telmisartan once a day (for protein levels in urine), Metoclopromide twice a day which helps for his digestion (his belly gets hard and bloaty right after he eats), and currently on 10mg once daily for Cushings (at 6am in the morning).

I have been driving back and forth from work everyday since starting the Vetoryl because I'm worried about this talk of adrenal rupture and necrosis and feel I need to check on him. He has shown no ill signs since starting the med but I am so worried about him having a reaction while I'm at work (8-5pm) to where I would be too late to help him. Am I being ridiculous?

Also his liver enzymes are SO HIGH that I inquired with the vet if he could have liver disease. He thought no based on all other findings and stated his gallbladder was normal on ultrasound. Could this be so high simply related to Cushings?

The vet wanted to recheck the ACHT test one month after starting the medication but I want to push for the 10-14 day mark like the medication says. There was also mention of checking Potassium levels (or maybe it was electrolytes) at that time as well: do many people also test for that with the first post-medication ACHT test?

I am in a hard place as I want him as comfortable and happy as he can be but the side effects scare me: and I know without getting the cortisol levels adjusted he will continue to get more out of wack. Any words of advice of knowledge you have would be amazing. Thank you all!

~Angelica


***
***
1/12/2020 ACTH

Pre 10.7
Post 14.8
Second Post 5.8

*ACTH Reference Range*
2-6 Pre
6-18 Post
18-22 Equivocal Post
>22 Post ACHT consistent with hyperadrenocorticism
/
1.5-6 Desired pre and post ACTH cortisol on *trilostane therapy

ACTH response test is only clearly positive (>22) in 30% of dogs with hyperadrenocorticism (HAC); equivocally positive in another 30% of dogs with HAC, and normal in 40% of dogs with HAC. If the ACTH response test is normal and HAC is still suspected, proceed with a low-dose dexamethasone suppression test.
*Recommendations for target cortisol levels on trilostane (Vetoryl) therapy vary. Per manufacturer, pre and post ACTH cortisol levels of 6-9 ug/dL (testing performed 4 hours post trilostane) may be sufficient for some animals if clinical signs are well controlled.

3/22/2020 Senior Screen Bloodwork + Urine

Glucose 102 (63-114 mg/dL)
SDMN 7 (0-14)
Creatnine .08 (.5-1.5)
BUN 15 (9-31)
BUN/Creatinine Ratio 18.8
Phosphorus 4.7 (2.5-6.1)
Calcium 10.9 (8.4-11.8)
Sodium 147 (142-152)
Potassium 5.5 (HIGH) (4-5.4)
Chloride 108 (108-119)
NA/K Ratio 27 (LOW) (28-37)
TCO2 (Bicarbonate) 18 (13-27)
Anion Gap 27 (HIGH) (11-26)
Total Protein 7.4 (5.5-7.5)
Albumin 3.6 (2.7-3.9)
Globulin 3.8 (2.4-4)
ALB/Glob ratio .9 (.7-1.5)
ALT 388 (HIGH) (18-121)
AST 38 (16-55)
ALP 2858 (HIGH, result verified by repeat analysis) (5-160)
GGT 5 (0-13)
Total Biliurubin 5 (0-.3)
Bilirubin Unconj .1 (0-.2)
Bilirubin Conj 0 (0-.1)
Cholesterol 415 (HIGH)(131-345)
Creatine Kinase 103 (10-200)
Hemolysis Index 2
Lipemia Index N
T4 1.4 (1-4)

WBC 12.1 (4.9-17.6 K/uL)
RBC 5.87 (5.39-8.7 M/uL)
HGB 15.6 (13.4-20.7 g/dL)
HCT 41.4 (38.3-56.5%)
MCV 71 (59-76 fL)
MCH 26.6 (HIGH) (21.9-26.1 pg)
MCHC 37.7 (32.6-39.2 g/dL)
Platelet 630 (HIGH - Platelets appear increased on the blood film) (143-448 K0uL)
Notes: Lipemia observes, may artifactually increase HGB, MCH, and MCHC

Glucose in urine: NEG
Specific Gravity: 1.02
Clarity: Clear
NEG for Blood, Ketones, Bilirubin
Protein: 2
PH: 7
No Bacteria, Crystals, Casts, Mucus seen in urine

Urine Creatinine 70.9
Urine protein 107.7
Urine Pro/Creat Ratio 1.5

Renal proteinuria:
UPC <.2 non-proteinuric
UPC .2-.5 borderline proteinuric
UPC >.5 proteinuric

3/26/2020 ACHT

Pre 4.9
Post 17.4
Second Post 21.1

[Harley PoMMom]

Hi Angelica,

Welcome to you and Chio! First let me commend you on being such a strong advocate for you sweet boy, we truly understand the love and bond you have with your precious Chio. We also can completely identify with the apprehension you feel with the vet, as many of us have felt that our vet didn't have the level of expertise that was sufficient to effectively direct our dog's treatment. I am relieved that you did push for that recheck of cortisol levels and the electrolyes at the 10-14 day window, that is an important step as, sometimes, a dog's cortisol can drop too low without showing many symptoms, also, it is vital that the cortisol be rechecked 30 days from treatment because cortisol can continue to drift downward during the first 30 days of treatment. With Chio's weight of 14 lbs, the 10 mg dose of Vetoryl does follow what is recommended. Now, a couple important facts regarding treatment; Vetoryl has to be given with a full meal to be properly absorbed, and those ACTH stimulation tests have to be performed 4-6 hours after the Vetoryl was given. Are both of these protocols being followed?

I need to ask a big favor, could you edit your post and include the reference ranges and units of measurement for the values you posted? Thanks, and as an example (these are random numbers): ALP 200 (50-100 U/L)

Dog's with Cushing's commonly have elevated liver enzymes, high cholesterol and triglyceride levels. They also have what is referred to as a "stress leukogram," which refers to a specific white blood cell distribution in the blood. This includes a high total white blood cell count with increased numbers of neutrophils (NEU) and monocytes (MONO) and decreased numbers of lymphocytes (LYM) and eosinophils (EOS).

Vetoryl is a strong drug and it does have some pretty scary side effects, however, adverse effects are usually not seen unless the proper treatment protocols are not followed. We have many members that are treating their cushdog with Vetoryl/Trilostane and are experiencing success. The key to facilitating safe and effective treatment is an experienced vet and an educated pet owner, so the best advice I can give you is to do your research on Cushing's, the treatment protocols, and how it is diagnosed. With treatment dogs with Cushing's can have a good quality of life and there is every reason to believe that they can live out their normal life span.

Please know you are not alone on this journey as we are right there beside you and if you have any questions do not hesitate to ask them.

Oh, here's a handy link to our Resource thread where you will find a wealth of information about Cushing's:http://www.k9cushings.com/forum/forumdisplay.php?f=10

Hugs, Lori

[ChiosMom]

Thank you Lori for your information and quick response! I have edited my post to include the ranges and notes from his testing, in the parenthesis. I made Chio's 2 week follow up ACTH test today for the 10th, which is exactly two weeks since starting his medication from March 28th. I also asked we check his electrolytes at that time as well. He will be given his pill at 6am with breakfast and I will be dropping him off at 10:00 for his test, so their blood collections should fall right in the parameters of that 4-6 hours window. He's been getting his pill every morning with food.

Does cortisol levels stay pretty consistent after the first 30 days of starting meds? I know you must keep up on checking his levels thereafter, but is the first month usually the time where bad or sudden reactions can occur? Have there been instances of a dog having a good response to meds (ie no outwardly warning flag signs) but then suddenly they go into adrenal rupture or necrosis?

I see I totally missed the section of his bloodwork for the NEU, MONO, etc levels, I have added them here:

% Reticulocyte 1.5%
Reticulocyte 88 (10-110 K/uL)
Retic HGB 26.7 (22.3-29.6 pg)
% NEU 73.7
% LYM 16.4
% MONO 6
% EOS 3.8
% BAS .1

NEU 8918 (2940-12670 /uL)
LYM 1984 (1060-4950)
MONO 726 (130-1150)
EOS 460 (70-1490)
BAS 12 (0-100)

Thank you!
Angelica

[Harley PoMMom]

Thank you Lori for your information and quick response! I have edited my post to include the ranges and notes from his testing, in the parenthesis. I made Chio's 2 week follow up ACTH test today for the 10th, which is exactly two weeks since starting his medication from March 28th. I also asked we check his electrolytes at that time as well. He will be given his pill at 6am with breakfast and I will be dropping him off at 10:00 for his test, so their blood collections should fall right in the parameters of that 4-6 hours window. He's been getting his pill every morning with food.

Thank you for adding those reference ranges and units of measurement, to me his blood-work is consistent of a dog with Cushing's, I do see that his potassium is high which could be from the Vetoryl, it's good that you're having his electrolytes rechecked as to keep an eye on that level.

Does cortisol levels stay pretty consistent after the first 30 days of starting meds? I know you must keep up on checking his levels thereafter, but is the first month usually the time where bad or sudden reactions can occur? Have there been instances of a dog having a good response to meds (ie no outwardly warning flag signs) but then suddenly they go into adrenal rupture or necrosis?

When low doses are used Vetoryl has a relatively low incidence of adverse effects, however, Hypoadrenocorticism can develop at any dose of Vetoryl and at any time during treatment which is why it is vital to get those ACTH stimulation tests performed at regular intervals and it is also paramount for a pet parent to be observant of their dog's outward appearance. If you would notice symptoms of adverse effects such as vomiting, diarrhea, lethargy, inappetence, or Chio simply not acting his ole self, stopping the Vetoryl is required.

We have seen on the forum where a dog is acting normally but their ACTH stim test showed that the cortisol dropped too low. When this happens, usually just stopping the Vetoryl for a week or so is enough time for those adrenal glands to produce a sufficient amount of cortisol. Also in this situation Vetoryl should not be restarted until an ACTH stim test reveals that there is cortisol being produced that requires a restart of Vetoryl. If the ACTH stim test does not affirm that the dog is producing enough cortisol than a glucocorticoid supplementation is required such as predinose. If the electrolytes are imbalanced than mineralocorticoid therapy is started, one of the drugs that can be used is Percorten-V.

You're doing a great job, Angelica! And remember we are here for you both.

Hugs, Lori

[ChiosMom]

Thank you for your info Lori!

Quick follow up: we did the two week ACTH test (and without having the actual results in front of me) came back that his levels dropped a lot from where they were pre-med but were still in a sufficient range (an "8" if my memory serves with the range ~1-10?) so the vet was very pleased. I have seen a noticeable change in his water and pee intake/outtake, and his mild incontinence has also improved.

I have noticed though that Chio appears to be losing weight: it was just a few ounces from his pre Vetroyl weight (13.9 lb) vs his last weight in at the two week test (13.6 lb) but since that was also a few weeks ago I have noticed still more visible weight loss. Nothing substantial (no muscle wasting that I can see, no gauntness, no visible bones or anything drastic as such) but he appears thinner through his neck/chest area in particular and his collar is also fitting looser. He still has a potbelly. I asked the vet at his 2 week test if losing weight with this medication was normal and he said no, but as Chio should ideally lose 1-2 pounds anyway it was a good thing.

Question: is it really a good thing? Is it normal to see weight loss in dogs starting medication? Could it be his body is changing and therefore this is a positive change and nothing to concern over? Has anyone else seen weight loss in dogs starting medication?

[Harley PoMMom]

Is there a way that you could get the actual results from that ACTH stimulation test? Regarding the weight loss, dogs normally do not lose weight with only 2 weeks of treatment, however, all dogs are different and will react differently on treatment. Is Chio eating normally? Did he have a ravenous appetite before treatment began? When is his next ACTH stim test scheduled for?

You're doing an awesome job!!

Lori

[ChiosMom]

Hello Lori,

It's been a rough couple weeks: I've had medical issues and unfortunately now I have more to worry about with Chio: the last week I noticed a general "off-ness" with Chio (I would say a feeling more-so than any clinical signs) but he got a little picky with his food for a few of those days. I thought maybe he was bored with his dry food as I started to supplement with boiled chicken and he wanted just chicken, but also could tell his allergies were in full force which I assume doesn't make him feel great either. I mentioned these things (plus a rash on his tail, which is suspected due to allergies) to my vet when I took him for his ~month ACTH followup since starting Vetoryl on 4/30/20 (couple days ago).

The ACTH test (I don't have the exact results again in front of me, apologies) was the same as before so no drop or increase in levels in comparison to his 2 week test, but unfortunately the blood work I had done at the same time to check electrolytes showed him to be slightly anemic (right at the cusp of normal, just a notch below), they suspect he also has a pancreatitis (I think due to another level on blood work, I will need to double check), and they were concerned as a fatty bump on his chest (which he's had for a few years) has noticeably increased in size. They decided to do an ultrasound to make sure there was no internal bleeding (anemia), and hopefully today I should get results on the pancreatitis. He has had no vomiting, diarrhea or history of pancreatitis in the past.

Yesterday I took him back for them to take a sample of the chest bump for biopsy as they were unable to do that the day before, and my vet apologized that he did not see this the day before on the ultrasound (spleen looked normal), but Chio's liver now has several "spots" on it as well as a general "textured" look that we did NOT see on another ultrasound we did back in ~February. The vet is concerned (due to the quickness of change), and suspects either regeneration due to the trilostane (more-so positive) or unfortunately liver cancer. He took a fine needle sample of one of the spots on the liver for biopsy, but apologized that unless he took a sample from a spot it could come back normal even if these spots are cancerous as they did not physically open him up to take the sample. Results on both biopsies should be received in 3-7 days.

Naturally, I am dreading the worse but staying as positive as I can. I've done research all last night and this morning, and see maybe these spots could be nodular hyperplasia? The vet and tech mentioned it could simply be progression of liver disease (remember his ALP numbers were super elevated back in March, and he has had an enlarged liver for at least ~2 years now), could be another symptom of Cushings as he has had a lot going on in the last couple months, or again: liver cancer. Comparing ultrasound photos online between each of these three posibilities doesn't help me as of course I'm not a vet. As of Thursday night we have started him on Denamarin and I made the decision as of yesterday morning to stop giving him the Vetoryl pills at this time. Note: after reading the Vetoryl insert again, it does say pancreatitis has occurred in dogs as a side effect in "foreign markets". Note also: this visit showed he did gain a few ounces back, so he's essentially at the same 13.9 lb weight hes been at consistently for several years.

Now, a few things I've read that nodular hyperplasia could caused elevated ALP. I am now wondering if the ACTH testing from January that was essentially negative for Cushings (cortisol normal), Feb ultrasound that showed enlarged but normal textured looking liver with enlarged adrenal glands, to which the positive ACTH test we did again in March (with the elevated ALP blood work) was really all not all strictly Cushings related but a problem manifesting in the liver over just a couple months? When Chio started with increased drinking/urination in March we thought Cushings again based on his other outwardly symptoms (plus the positive ACTH), but could that have been these tumor (benign or cancerous)/nodular/spot things forming in the liver at that time causing it? Perhaps giving a false ACTH readings? I worry we started treating for Cushings premature without ruling out a new possibility of liver disease, failure, cancer etc?

Any insight, thoughts, advice? I'm scared

[labblab]

Hello Angelica, and a belated welcome to you and little Chio — I’m sorry I’ve not had the chance to greet you before this. I hope that Lori will also be stopping by soon, but I just wanted to let you know that I’m also so glad you’re here. I’ll be waiting until you receive these test results before drawing any big conclusions. But I do believe that Cushing’s itself may still be accounting for the laboratory and ultrasound irregularities. Cancer may be a possibility, but we do know that Cushing’s can produce some distinct changes in liver images. So there may not be anything more sinister at play here.

Do let us know as soon as you get the test results back. And please do try to provide us with the exact numbers on those two monitoring ACTH tests. It’s really hard to evaluate the benefit of the Vetoryl treatment without knowing exactly what the effect on Chio’s cortisol has been. In the meantime, I won’t tell you not to worry because that’s probably impossible (I am a born worrier, myself!). But please know that we’ll do our best to help you sort out the results when you get them, and to plan for the best path forward.

Marianne

[Harley PoMMom]

Hi Angelica,

I'm glad that Marianne has posted to you and I agree with what she has said, Cushing's can indeed cause changes to the liver. There is one question that I have, did Chio have a ravenous appetite before treatment of Vetoryl began?

Hugs, Lori

[ChiosMom]

Thank you to you both for your responses, please see below the ACTH test (1st check up at the two week mark starting Vetoryl) for 4/10/20:


Baseline Pre 1.6
Post 7.4
Second post 8.0

and most recent ACTH that coincided with the abnormal bloodwork (4/30/20):

Baseline Pre <0.5<
Post 4.7
Second 6.3


"User are instructed to start the ACTH stim test 4-6 hours post-dose, with a target post-ACTH cortisol of 1.45-5.4 ug/dl. A post-ACTH cortisol between 5.4 and 9.1 is acceptable if the clinical signs are controlled..."


I didn't notice it at first but I am unsure what this means on the second ACTH test: "Baseline Pre <0.5<"

No biopsy news as of today, but his pancreatitis test (CPL) came back slightly elevated at 300. So not super terrible, but recommended to change to a GI support diet over the renal diet he was on at this time.

I have reviewed his bloodwork results for the anemia, and those levels show very slight anemia with an increase in reticulocytes so it appears his body knows of the anemia (pending cause) and is working to improve. Re: anemia, is fecal occult blood test was negative. I went over many different questions with the vet today but bottom line is that we're hoping the cytology on the liver sample (and histology on the chest lump) will both give us a definitive as to what's happening at this point. Staying positive it's not cancer...

As far as appetite goes, he has always been voracious and food motivated (even when I got him around ~2 years old) and over the last two days his appetite has increased to his own level of normalcy. He seems overall happier and more alert the last couple days also, so again just trying to stay upbeat and not think of the possible negatives until we know some answers.

~Angelica