New to Forum. General Questions

[kjlucky]

Hi,

I’m new to the Forum as far as positing goes, but I’ve read a bit of it in the past.

My dog, Lucky, who is a 13-year-old Chihuahua mix, was diagnosed with Cushing’s last November. Always a thirsty dog, she became so thirsty she was drinking from puddles while outside. That was the only symptom at the time except for some minor weight gain — she went from 12 to 13 pounds. The doctor dismissed Cushing’s based on her CBC results, but I pushed for the ACTH test. She tested at 17.6, and was put on Vetoryl at 10 mg. It’s pituitary dependent Cushing’s as she had an ultrasound of her abdomen and no adrenal tumors were detected.

She has been tested 3 times since going on the Vetoryl (results below). Since the Cushing’s diagnosis, she was also diagnosed in April with a leaky heart valve after a heart murmur was detected. She is on 2.5 mg of Enalapril. She was also diagnosed with chronic pancreatitis in May through blood work after intermittent bouts with diarrhea since the beginning of this year. Lucky was put on a low-diet prescription diet and a pre- and probiotic after the CP diagnosis. Her stools have mostly been good since then.

Since being on the Vetoryl she has also had a few CBC panels. There were some increases in levels which are consistent with Cushing’s but nothing crazy and nothing that alarmed the vet.

Her latest ACTH test (her third) had her cortisol levels at their lowest levels since she started treatment last November. The vet has switched her to 5 mg of Vetoryl, which I will start tomorrow. She said you never want to get too low in the test results and that a dog’s reaction to the medication can change over time.

Here are the results of the three ACTH tests she has had since going on Vetoryl — starting with oldest to newest.

November Results (after two weeks on Vetoryl)
CORTISOL
SAMPLE 1:
2.2 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1 for Vetoryl)

CORTISOL
SAMPLE 2
4.2 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1 for Vetoryl)

March Results
Cortisol Sample 1
3.7 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1 for Vetoryl)

Cortisol Sample 2
6.0 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1 for Vetoryl)

June Results
CORTISOL 1 —1.1 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1)
indicate optimal control.

CORTISOL 2 — 3.4 ug/dL (Optimal Pre & post cortisol levels between 1.5-9.1)
indicate optimal control.

Clinically, she is doing generally okay. She is always wagging her tail and all my neighbors are astonished when I tell them how old she is.

But she did gain two pounds since the beginning of the year and is now at 15 pounds. She still likes to drink a lot of water, but she doesn’t drink from puddles anymore. Since I adopted her 10 years ago, she has always had a healthy appetite and that has not changed. (I only feed her kibble, no treats).

Among the changes I do notice since the Cushing’s diagnosis — besides weight gain and the begging for water— is occasional restlessness at different times of the day/night. She also seems to be hotter, particularly now that it’s summer. Se prefers to be on the floor near the fan rather than the couch. She also is reluctant to climb stairs, although some days she does not resist and happily goes up them. She is also a bit more clingy. Her demeanor changes a lot, day to day— although she never seems unwell or unhappy, just a bit different than before the diagnosis.

I’m very nervous about lowering the dose of the Vetoryl, considering her Cushing’s symptoms are still there and are probably responsible for the chronic pancreatitis. Curious as to what Forum members think about the lower dose? Also, any insight into the changes I’ve noted in her since the Cushing’s diagnosis, would be appreciated. Are these normal with Cushing’s dogs even though they are on medication?

Thank you in advance for your responses.

[labblab]

Hello, and welcome to you and little Lucky! I’m afraid I only have a moment to type right now since I’m headed out the door for an appointment. However I wanted to quickly tell you that I’ve moved your thread here, to our main discussion forum. This way, our members will be more likely to see your post and respond. I’ll return, myself, a bit later on. But in the meantime, we’re really glad you’ve joined us!

Until later,
Marianne

[Squirt's Mom]

Hi and welcome to you and Lucky!

The ACTH results are good so no worry there. So you can identify when the cortisol has fallen too low the signs you will see are loose stools/diarrhea, nausea/vomiting, loss of appetite, and/or lethargy. Elevated cortisol is not fun but when this hormone drops too low that is a life-threatening situation so always be on the lookout for any of these signs and if you see them do not give any more Vetoryl (Trilostane) and call the vet if things do not turn around very soon.

You said - "The doctor dismissed Cushing’s based on her CBC results, but I pushed for the ACTH test. She tested at 17.6" - can you give us the ranges used on that ACTH? Usually 18 is the upper limit so 17.6 would be negative or borderline at best. My second pup tested at greater than 50 - the range only went to 50 from that lab. My first cush pup tested at a little over 18 the first time and was considered borderline so I held off treatment and am glad I did because her cortisol was elevated as the result of a tumor on her spleen. I am assuming everything on Lucky's ultrasound was normal? Was there any mention of the adrenal glands being enlarged? That is normal for a cush pup - with pituitary both are enlarged, with adrenal one is enlarged and the other much smaller or even atrophied.

Would you mind posting the abnormal values from the CBC? If she had a test that shows things like BUN, ALP, ALT, CHOL, etc we would be MOST interested to see those abnormal values as well. Please include the little letters and normal ranges for each. It will look something like -

CHOL 154 ug/dl 115-320
ALP 1500 m/mnol 250- 400

Assuming the diagnosis is correct there is no reason that I can see to lower the Vetoryl dose - that is not typical protocol at all UNLESS there are signs like the ones I mentioned above OR the ACTH shows the cortisol has dropped to low. Lucky's cortisol is not even at optimal range since you are still seeing signs so lowering the dose dosen't make sense to me. That upper number of 9.1 is if, and ONLY IF, all signs are well controlled. Otherwise you want it under 5.4 ug/dl. The things you have mention tell me that her dose does not need to be lowered at this time. That 3.4 ug/dl in June is perfect.

You say she "begs" for water...she should ALWAYS have fresh water available. Cush pups don't pee a lot because they drink a lot; it is the exact opposite - the drink a lot because they pee a lot. They are going to pee and must have water to stay hydrated. Never ever withhold or ration water with a cush pup. ;)

Cush pups have a hard time regulating their body temp and do not handle the heat well at all. They will seek cool places to lay. They also lose muscle mass especially in the back legs so they don't jump, climb stairs, etc as well as they used to. Sometimes this will improve with treatment, sometimes not.

I'm glad you found us tho I am sorry you find the need for a group like this. Cushing's can be handled and your baby live our her normal life span and beyond barring any complications. Feel free to ask any questions you have and we will do our best to help.

Hugs,
Leslie

[labblab]

OK, I’m finally back again, and so glad to see that Leslie has had the chance to reply to you, too. She has asked some great questions, and like her, I’m anxious to learn more about Lucky’s diagnostic testing. Also like her, I’m especially curious as to whether there were any lab abnormalities at all aside from the ACTH test that you are telling us was “positive.” The vast majority of Cushing’s dogs exhibit elevated ALKP (sometimes abbreviated as ALP) on their blood chemistry panels. For Cushpups, this is a marker that reflects the disease’s effect upon the liver. ALKP can be very highly elevated by Cushing’s, and other liver markers often show mild to moderate elevation. Cholesterol is also frequently elevated on chemistry panels. Turning to the blood cell counts contained on a CBC, platelets are often elevated, and there is also a particular abnormal pattern of white blood cells that is common with Cushing’s. So the long and the short of this is: if Lucky truly has Cushing’s, it would be surprising if all of her pretreatment bloodwork was normal.

It would also be somewhat surprising if her ultrasound didn’t show enlargement of her adrenal glands. Although not always the case with pituitary Cushing’s (especially early on), the majority of pituitary cases do show bilateral enlargement. So even though adrenal tumors have been ruled out as a cause of Cushing’s for Lucky, I’m searching in your notes for laboratory or imaging abnormalities that are consistent with the pituitary form of the disease. For that reason, I’ll be interested to hear more about that diagnostic phase.

However, turning now to the Vetoryl, here’s a condensed summary of Lucky’s ACTH testing:


November Results (after two weeks on Vetoryl)

SAMPLE 1:
2.2 ug/dL

SAMPLE 2:
4.2 ug/dL

March Results

Sample 1:
3.7 ug/dL

Sample 2:
6.0 ug/dL

June Results

Sample 1:
1.1 ug/dL

Sample 2:
3.4 ug/dL

I believe I’m correct that, up until now, she’s consistently been taking 10 mg. daily? If so, I actually do agree with your vet that I’d want to decrease her dose right now, at least temporarily, and this is why. While taking the same dose from November to March, her cortisol readings actually elevated somewhat. However, from March to June, her cortisol level has now dropped quite a bit, even without any dosing change. You really don’t want it to continue this same trend and drop even further. So I do agree with your vet that, for safety’s sake, I’d decrease her dose for the time being. Reducing the dose fully by half may turn out to be too great a decrease, and retesting in the future may prompt yet another increase — perhaps to somewhere in between. But really, you don’t want that cortisol to keep additionally dropping much lower now.

However, having said that, I do agree with Leslie that her June post-ACTH result was right in the middle of the prime therapeutic range. Have Lucky’s observable Cushing’s symptoms stayed pretty consistent since November? If so, it may just be taking a lengthier time for them to resolve for some reason. However, if they’re actually getting worse, I can’t really explain why they’d be advancing during a time period when her cortisol level was theoretically under optimal control. So that’s yet one more puzzle piece to explore.

OK, I will close for now. But yet again, I want to tell you how glad I am that you’ve found us, and we’ll be awaiting further info about your sweet girl.

Marianne

[kjlucky]

Thank you Marianne and Leslie for your responses. Very helpful.

In answer to your questions:

The high-end of the range of the initial Cushing’s test was 17. She tested at 17.6. I recall the vet saying at the time of the diagnosis, “She didn’t break the bank with her number, but it is still above the acceptable range.” I don’t have copies of those results, so I don’t know what the lower range is, but 17 was definitely the highest on the scale used for that test.

I should have been clearer in my original post, Marianne — I suspected for a long time that Lucky had Cushing’s, but the blood work was normal. Then when I pushed for Cushing’s test, a CBC was done that same day (results are below) and the results showed elevated levels of BUN as well as the BUN/CREATINE RATIO. As you will see by looking at the subsequent results, other numbers consistent with Cushing's have increased as well.

As for the imaging, no abnormalities of her organs, but the vet did say, and I’m paraphrasing here: “Her adrenal glands for a Cushing’s dog are in pretty good shape.” So that says to me she did note some enlargement, but it wasn’t an alarming amount.

She has consistently been on a single dosing 10 mg of Vetoryl until today when I started the single dosing of 5 mg.

Lucky’s observable Cushing’s symptoms have stayed consistent from November to now.

As I mentioned in my original post, after one month on the Vetoryl she began exhibiting intermittent diarrhea. Her stool tested positive for CDIFF, but no indication of toxins. The vet said many dogs test positive for CDIFF and the time to be worried is when they test positive for toxins. The diarrhea comes and goes. Last month, blood work revealed that she has chronic pancreatitis. Thus the switch to low fat diet and the pre and probiotics.

Here are the test results:

JUNE BLOOD WORK— Latest Test

A/G Ratio 1.0 0.8 - 2.0
ALB 3.4 g/dL 2.7 - 4.4
ALKP 186 IU/L H 5 - 131
ALT 53 IU/L 12 - 118
AST 27 IU/L 15 - 66
B/C Ratio 32 H 4 - 27
BUN/UREA 42 mg/dL H 6 - 31
Ca 10.2 mg/dL 8.9 - 11.4
Chloride 110 mEq/L 102 - 120
CHOL 166 mg/dL 92 - 324
CK 215 IU/L 59 - 895
CREA 1.3 mg/dL 0.5 - 1.6
GLOB 3.4 g/dL 1.6 - 3.6
GLU 89 mg/dL 70 - 138
Na/K Ratio 28 27 - 38
PHOS 3.7 mg/dL 2.5 - 6.0
Potassium 5.2 mEq/L 3.6 - 5.5
Sodium 144 mEq/L 139 - 154
TBIL 0.1 mg/dL 0.1 - 0.3
TP 6.8 g/dL 5.0 - 7.4
Ca (CORR) 10.3


ABS BASO 0 /uL 0 - 150
ABS EOS 606 /uL 0 - 1200
ABS LYMPHS 1313 /uL 690 - 4500
ABS MONOS 606 /uL 0 - 840
ABS NEUTS 7575 /uL 2060 - 10600
BASO 0 % 0 - 1
EOS 6 % 2 - 10
LYMPHS 13 % 12 - 30
MCH 23.7 pg 19 - 28
MCHC 33 g/dL 30 - 38
MCV 72 fL 58 - 79
MONOS 6 % 3 - 10
NEUT BANDS 0 % 0 - 3
PLATELETS 456 10^3/uL H 170 - 400
RBC 5.9 10^6/uL 4.8 - 9.3
WBC 10.1 10^3/uL 4.0 - 15.5
NEUT 75 % 60 - 77
HEMOGLOBIN 13.9 g/dL 12.1 - 20.3
PLATE(EST) Increased
HEMATOCRIT 42 % 36 - 60

MARCH BLOOD WORK

Total Protein 6.5 5 - 7.4 g/dL
Albumin 3.7 2.7 - 4.4 g/dL
Globulin 2.8 1.6 - 3.6 g/dL
A/G Ratio 1.3 0.8 - 2
AST (SGOT) 36 15 - 66 IU/L
ALT (SGPT) 63 12 - 118 IU/L
Alk Phosphatase 137 5 - 131 IU/L
GGTP 6 1 - 12 IU/L
Total Bilirubin 0.1 0.1 - 0.3 mg/dL
Urea Nitrogen 44 6 - 31 mg/dL
Creatinine 1.5 0.5 - 1.6 mg/dL
BUN/Creatinine Ratio 29 4 - 27
Phosphorus 4.3 2.5 - 6 mg/dL
Glucose 79 70 - 138 mg/dL
Calcium 10.3 8.9 - 11.4 mg/dL
Magnesium 2.1 1.5 - 2.5 mEq/L
Sodium 148 139 - 154 mEq/L
Potassium 4.7 3.6 - 5.5 mEq/L
Na/K Ratio 31 27 - 38
Chloride 108 102 - 120 mEq/L
Cholesterol 251 92 - 324 mg/dL

WBC 8.8 4 - 15.5 10^3/uL
RBC 6.6 4.8 - 9.3 10^12/L
Hemoglobin 16.5 12.1 - 20.3 g/dL
Hematocrit 48 36 - 60 %
MCV 73 58 - 79 fL
MCH 25.1 19 - 28 pg
MCHC 34 30 - 38 g/dL
Platelet Count 447 170 - 400 10^3/uL
Platelet EST Increased
Neutrophils 69 60 - 77 %
Bands 0 0 - 3 %
Lymphocytes 19 12 - 30 %
Monocytes 6 3 - 10 %
Eosinophils 6 2 - 10 %
Basophils 0 0 - 1 %
Absolute Neutrophils 6072 2060 - 10600 /uL
Absolute Lymphocytes 1672 690 - 4500 /uL
Absolute Monocytes 528 0 - 840 /uL
Absolute Eosinophils 528 0 - 1200 /uL
Absolute Basophils 0 0 - 150 /uL

NOVEMBER 2018 BLOOD WORK — SAME DAY AS CUSHING’S DIAGNOSIS.

TotalProtein 6.9 5.0-7.4 g/dL
Albumin 4.0 2.7-4.4 g/dL
Globulin 2.9 1.6-3.6 g/dL
A/G Ratio 1.4 0.8-2.0
AST (SGOT) 44 15-66 IU/L
ALT (SGPT) 41 12-118 IU/L
Alk Phosphatase 63 5-131 IU/L
Total Bilirubin 0.1 0.1-0.3 mg/dL
BUN 38 (HIGH) 6-31 mg/dL
Creatinine 1.3 0.5-1.6 mg/dL
BUN/ Creatinine Ratio 29 (HIGH) 4-27
Phosphorus 4.3 2.5-6.0 mg/dL
Glucose 85 70-138 mg/dL
Calcium 10.7 8.9-11.4 mg/dL
Sodium 144 139-154 mEq/L
Potassium 4.8 3.6-5.5 mEq/L
NA/K Ratio 30 27-38
Chloride 108 102-120 mEq/L
Cholesterol 244 92-324 mg/dL
CPK 330 59-895 IU/L


WBC 7.1 4.0-15.5 10^3/uL
RBC 6.4 4.8-9.3 10^6/uL
HGB 16.7 12.1-20.3 g/dL
HCT 47 36-60 %
MCV 74 58-79 fL
MCH 26.0 19-28 pg
Test Requested Results Adult Reference Range Units
Complete Blood Count
WBC 7.1 4.0-15.5 10^3/uL
RBC 6.4 4.8-9.3 10^6/uL
HGB 16.7 12.1-20.3 g/dL
HCT 47 36-60 %
MCV 74 58-79 fL
MCH 26.0 19-28 pg
MCHC 35 30-38 g/dL
Platelet
Count
346 170-400 10^3/uL
Platelet
Estimate
Adequate
Neutrophils 4,970 70 2060-1060
0
/uL
Bands 0 0-3
Lymphocyt
es
1,349 19 690-4500 /uL
Monocytes 426 6 0-840 /uL
Eosinophils 355 5 0-1200 /uL
Basophils 0 0 0-150 /uL


Thanks again!
Karen

[labblab]

Karen, thanks so much for all this additional information! You’ll see that I’ve taken the liberty of editing your post so as to “bold” those blood values that are abnormal for Lucky. There are very few that I saw — if I’ve missed any, please do note them.

Before writing any more, you need to know that I am not a vet, and I have no professional vet-related training. But after many years of viewing Cushing’s dogs’ labs on this and related internet forums, I must tell you that I don’t believe that Lucky’s progression of values are consistent with the disease as I have seen it.

Apparently Lucky’s original outward symptoms were excessive thirst, minor weight gain, vague restlessness, feeling hot, and perhaps reluctance with stairs? But at the time of her diagnostic testing in November, the only lab abnormality was elevated BUN and BUN/creatinine ratio. There are multiple conditions that can increase thirst, and for a dog with elevated BUN and absolutely no other lab abnormalities, I don’t believe Cushing’s would typically ever be on the radar. At all. If anything, I would think some type of primary kidney issue might be considered. In view of the thirst and BUN, I’m wondering whether a SDMA blood test was performed? It’s a relatively new test that can reflect early kidney dysfunction prior to the development of major lab abnormalities.

However, you did proceed with an ACTH — and here’s Problem #2. The result was very minimally elevated. However, “false positives” can occur and are always a risk in the presence of other systemic illnesses that place stress on the body. That’s why the presence of multiple consistent symptoms and lab abnormalities are such an important part of making a Cushing’s diagnosis in conjunction with a diagnostic ACTH. We may suspect that Lucky was harboring CDIFF, and perhaps even chronic pancreatitis at that time. So there may have been causes for the elevated cortisol other than Cushing’s itself.

Problem #3 relates to the ultrasound. Canine adrenal glands are notoriously difficult to visualize, and general practice vets often lack the state-of-the-art equipment that’s needed to get really accurate images. Your vet may, in fact, have been able to get good views, but I would pin her down as to exactly what she was able to see. If Lucky’s adrenal glands basically looked normal, that’s another strike against a Cushing’s diagnosis.

Problem #4 is that the progression of her lab values remains perplexing. Aside from the BUN, I’m only seeing subsequent minor elevations in her platelets and Alk Phos. Other than that, her labs still remain totally normal (although I’m guessing there are some diagnostic pancreatic values that are missing from this list?). I do believe the mildly elevated Alk Phos could perhaps be linked to the pancreatitis. But here’s the kicker: Vetoryl treatment itself has been associated with increases in liver enzymes and BUN. Here’s a quote from a technical brochure published by Dechra, the manufacturer of Vetoryl:


As with all drugs, side effects may occur. In field studies and post-approval experience, the most
common side effects reported were: anorexia, lethargy/depression, vomiting, diarrhea, elevated liver enzymes, elevated potassium with or without elevated sodium, elevated BUN, decreased Na/K ratio, hypoadrenocorticism, weakness, elevated creatinine, shaking, and renal insufficiency. In some cases, death has been reported as an outcome of these adverse events. VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant dogs. Refer to the prescribing information for complete details or visit www.Dechra-US.com.

I don’t know that Lucky’s elevated BUN has actually ever been all that sinister, especially since her creatinine level has remained within normal limits. By any chance, do you feed her really high protein food? At any rate, I just don’t know how much attention it should really warrant. But above all, I don’t believe it would typically prompt the suspicion of Cushing’s in the absence of other consistent lab abnormalities.

So the bottom line — as I know is obvious by now — I really, really question the validity of the Cushing’s diagnosis, especially since the outward symptoms that first concerned you haven’t resolved with Cushing’s treatment, and the mildly elevated Alk Phos has only developed subsequent to starting the medication, and in conjunction with the identification of chronic pancreatitis. I don’t wish to upset you by questioning your current treatment path, but in good conscience, I do need to share my concerns.

So there you have it, and I’m definitely happy to discuss all this further if you wish to do so! But after writing what looks like a book, I’ll sign off for now...

Marianne

[kjlucky]

Hi Marianne,

Many thanks for the detailed response. I will consult with my vet. We have good communication and as you see I'm very on top of Lucky's condition in terms of bringing her to the vet for STIM tests and blood work and regular checks. I also plan on consulting a vet who is a specialist with Cushing's patients.

In the meantime, it is best for me to discontinue participating in this Forum as it really triggers my anxiety.

All the best to everyone with their beloved animals.

And thanks again.

KJ

[labblab]

Dear Karen,

I was fearful that my comments would be upsetting to read, but as I wrote earlier, I felt that I had a duty to tell you about my concerns. I'm really glad that you'll be discussing things further with your vet, and I'm especially relieved to hear that you'll be consulting a Cushing's specialist. Cushing's is such a tricky disease in so many ways, and receiving input from a clinician who specializes in the area can be so very helpful. No matter whether I am "on base" or "off base" with my own concerns, I'm hopeful the specialist will be able to strengthen your confidence in the path forward, whichever way it leads. And if Cushing's remains a treatment focus for Lucky, I hope that perhaps you'll wish to return to us at some point. I am always hoping to learn more, myself, and would welcome hearing the input from your specialist, especially if it's to correct misstatements I may have made.

I am such a worrier myself that I do understand and respect your decision to pull back from us right now. I think you're doing the right thing by pursuing your questions with the professionals. But please know that we'll always welcome you back at any time, especially if there's information that I've given you that ought to be clarified.

In the meantime, best wishes to you and to Lucky, and we'll surely be hoping that all goes well for you both.
Marianne