Diagnostic Plan to Rule Cusahings In/Out

[PrincessDangers]

Hello,

A tentative diagnosis of Cushings has been discussed for the past three years for my beloved dog, based primarily on elevated ALP results that are doubling each year. She did not have bloodtests last year (I was trying to avoid non-emergency vet visits because of the pandemic). We have moved multiple times in the past few years so these results are all from different labs/vets.

Is there a preferred order of operations for ruling this disease in or out?

My dog is nervous of vet visits and I don't want to torture her unnecessarily. I'm not putting her through diagnostics just out of curiosity. The tests are only justifiable if it keeps her healthy and improves her quality of life.

My dog has luxating patella and chronic ear infections but is otherwise perfectly healthy.

She does drink and pee much more than other dogs, but her urine is not dilute. The frequent urination is not a lifestyle problem for me. If fine taking her out many many times a day and giving her wee pads for emergencies. She has hind end weakness, but she also has arthritis (she just started adequan).

Her appetite is normal. She has a beautiful full coat.

The rest of her blood work is "very good" according to the vet. Her Globulin, total protein, Creatine Kinase, and Reticulocytes are within normal but a bit on the higher side. Her hemaglobin and MCH are within normal but a tiny bit low.

4 years of age, 2015 ALP: 36
5 years of age, 2016 ALP: 70
6 years of age, 2017 ALP: N/A
7 years of age, 2018 ALP: 450 *Advised to revisit the issue if she had any strange symptoms. Cushings was mentioned, but more likely, she suspected it was due to bone rebuilding (my dog has luxating patella/arthritis)
8 years of age, 2019 ALP: 777 *Suspected Cushings based on blood work but not urine. The vet said that she does not recommend testing/treating at this age if the pet is not really suffering (because they usually die of something else first)
9 years of age, 2020 ALP: N/A
10 years of age, 2021 ALP: 1,686 *Suspects Cushings based on blood work but not urine. She has a lot of white blood cells in her urine but no bacteria. Started a course of Clavamox in case of infection.

This vet would like to do an ultrasound as the next step rather than a Cushings test. Also, she wants to collect a sterile sample at that time.

The ultrasound is going to be stressful, but I think it is worth doing.

This is the second vet who has told me they don't like/trust the stim test. She said sometimes it is positive one year then negative the next and she'll suspect Cushings for years but never get the diagnostic proof necessary to support treating the dog with medication for it. If the adreanal glands are enlarged, that might support a Cushings diagnosis and she would recommend the stim test. Then, she said that if they're not enlarged, that does not rule out Cushings and she would recommend the stim test. So, that's confusing.

It is difficult for me because I have never met this vet. We've only spoken on the phone. I don't understand why a sterile sample is needed if there were no bacteria in her urine. That's a really unpleasant thing to do.

[labblab]

Hello, and welcome to you and your girl! As you’re probably aware, the goal of Cushing’s medication treatment is to alleviate symptoms as opposed to “curing” the disease itself. So prior to launching into further diagnostics, I have a couple of questions for you. What is the expected lifespan for your breed of dog (in other words, at age 10 is she already approaching a more elderly status)? And secondly, even if Cushing’s were to be confirmed, would you choose to start medicating her at this point?

Cushing’s is typically a very slowly developing disease. Your dog’s gradually increasing ALP over the period of six years certainly does qualify as very slow development if Cushing’s is the cause. And if she otherwise doesn’t seem to be uncomfortable, herself, by the excessive thirst and urination, then I’m not sure the trade off associated with treatment would yet seem worth it to you in the absence of additional observable symptoms. Frequent vet visits and blood tests are initially required to ensure proper monitoring of the medication, and that would be stressful for a dog who is fearful. Also, for seniors, arthritic issues may actually become more apparent when cortisol levels are lowered. For younger dogs, a chief goal of Cushing’s treatment is to prevent longterm internal systemic damage that Cushing’s can cause. But for older dogs, my personal opinion is that present comfort and quality of life take precedence. If Cushing’s is making a dog of any age visibly uncomfortable, I would opt to treat. But in the absence of observable discomfort in an older dog, I would likely be more cautious.

There are a couple of exceptions to my “observable discomfort” yardstick. If a Cushing's dog of any age is suffering from either high blood pressure or significant protein loss into the urine, these can be important reasons to start treatment in their own right. This is because these two “silent” conditions can lead to other serious problems such as blindness and kidney dysfunction.

In terms of your own dog’s situation, I would never say that an abdominal ultrasound would be a bad idea for a dog who has exhibited consistently increasing ALP levels over six years. If not Cushing’s, then the ultrasound might reveal some other abnormality that’s at play, and you might welcome that information. If you do opt for the ultrasound, I’d go ahead and also opt for the sterile urine sample so that a really accurate culture could be done. You say that your dog’s urine is not dilute — which seems surprising with excessive thirst/urination — but a culture performed on a sterile sample could definitively rule out infection.

As far as specific Cushing’s testing, however, one option you might consider prior to anything else is a urinary cortisol to creatine ratio (UC:CR). This test is best performed using a pooled sample of urine that the owner has collected at home (first pee of the morning, pooled over three days). Stress has to be minimized for this test to be accurate, so the sample definitely should *not* be collected at the vet’s office. But if you collect the pee at home, then you can take it in for analysis. A positive result on this test does not confirm Cushing’s, but a negative test is 99% accurate at ruling out Cushing’s. So before any other testing at all, you might want to consider this low-stress diagnostic.

If you do opt for diagnostic blood testing at any point, I would think a low dose dexamethasone suppression test (LDDS) would be the option preferred over the ACTH stimulation test. For a dog without any other known health issues, the LDDS is much less likely than the ACTH to return a “false negative” in a dog who truly has the disease. I’m giving you a link below that leads you to a brochure published by the maker of a Cushing’s treatment medication that discusses these three diagnostic testing options in greater detail (UC:CR, LDDS, ACTH). You’ll find the table that compares them on page 5 of the brochure (“Confirming the Diagnosis”).

https://www.animalhealthinternational.com/animalhealthinternational.com/media/Animal-Health-International/Training/Dechra/VETORYL-Technical-Brochure-SPreads-v6-15-15.pdf

I know I’ve already written quite a bit here, so I’ll take a breather for now! Please do let us know of any additional thoughts or questions that you may have, though, as we are very happy to discuss everything in further detail. And once again, we’re very glad you’ve found us!

Marianne

[Harley PoMMom]

Hi and welcome to you and your precious girl!

Diagnostic testing usually isn't recommended unless the dog is displaying strong obvious signs of Cushing's. One reason is because the goal of treatment is control those bothersome symptoms so if the dog is not exhibiting the manifestations of this disease it would be hard to judge how well treatment is going.

An ultrasound, I believe, would be useful as it could get a good look at those internal organs and see if there would be other reasons for her symptoms. Another test you could consider is the UC:CR, if a dog has a normal reading than Cushing's is highly unlikely. This type of test is not invasive and only requires some urine samples taken at home. Ideally 3 morning pooled urine samples are collected by the owner at home and kept refrigerated until the samples can be taken to the vet office.

You posted that her urine is not dilute, could you tell us what her USG (urine specific gravity) is? It should be on the urinalysis report. Also, could you tell what breed your sweet girl is?

Again, welcome to our family and please know we will help in any way we can.

Hugs, Lori

[PrincessDangers]

Thank you so much for all of this information and the quick reply!

She is a 40 pound mixed breed dog. Medically, I don't know what her life expectancy is. Personally I hope she lives forever with a great quality of life. She's a very happy playful girl with a beautiful temperament. Her vet said that the medication for Cushing's is really well tolerated but, as you said, the ongoing testing associated with it is sometimes *prohibitive*

I had a much larger dog who lived to 18 and was in great spirits until the last week of her life. I think a her longevity was due in part to having had cancer twice and super frequent check ups and ultrasounds twice a year. Nothing went unnoticed for long. That dog was always happy to go to the vet though.

My possible Cushing's patient dog has been incredibly healthy. Her veterinary needs have been almost non-existent. Her current course of antibiotics is the first she's ever taken (though she's had ear drops).

The vet hasn't sent me the urine tests results. I will request them. The tech said it was their "regular" urine test when I dropped it off, but it was a single sample of first pee of the morning. I will ask about the three day pooled urine test. Of the test that was done, her vet said that it is not indicative of Cushing's but also "a urine test doesn't rule it out because Cushing's can do whatever it wants".


That sample was yellow, but there have been days that her urine (which I can see on the wee pad) appeared clear to me. I'm not sure what to make of that.

Since she is afraid of going to the vet (mostly of the car ride), I just want to be efficient with the diagnostics and as kind as possible to her. Thank you again for this resource.

[PrincessDangers]

Yes, I think there is benefit to taking a look around in there. The vet mentioned "maybe GI, maybe gallblatter..." and several other things she'd like to take a look at.

I'll request the urinalysis report.

She is a mixed breed. According to her Embark test, she is about half American Pit bull Terrier, and the other 50% is Shih-Tzu, American Eskimo Dog, and Small Poodle. She has long scruffy fur and looks like the cutest muppet. I love her so much.

Thank you for your help.

[Harley PoMMom]

Wow, 18 years old, that's a true testament of your love and devotion, your girls are very lucky to have you as their pet parent!

Was a SDMA test included with the chemistry blood panel? If not, this may be another test to consider, these results help show the function of the kidneys and are a better marker for kidney disease. Here's a link with information regarding this type of test: https://www.idexx.com/en/veterinary/reference-laboratories/sdma/sdma-faqs/

Hugs, Lori

[PrincessDangers]

Wow, 18 years old, that's a true testament of your love and devotion, your girls are very lucky to have you as their pet parent!

Was a SDMA test included with the chemistry blood panel? If not, this may be another test to consider, these results help show the function of the kidneys and are a better marker for kidney disease. Here's a link with information regarding this type of test: https://www.idexx.com/en/veterinary/reference-laboratories/sdma/sdma-faqs/

Hugs, Lori

Looking back at her pictures I see that she was ancient looking, but I did not see it at the time at all!

Yes, it was included. This test was through IDEXX. It says "IDEXX SDMA" with a reference range of 0 - 14 (not sure if that's standard). Her result was "3" With this note... "SDMA and creatinine are within the reference interval; impairment of GFR is unlikely. Recommended next step: evaluate complete urinalysis."

[PrincessDangers]

Wow, 18 years old, that's a true testament of your love and devotion, your girls are very lucky to have you as their pet parent!

Was a SDMA test included with the chemistry blood panel? If not, this may be another test to consider, these results help show the function of the kidneys and are a better marker for kidney disease. Here's a link with information regarding this type of test: https://www.idexx.com/en/veterinary/reference-laboratories/sdma/sdma-faqs/

Hugs, Lori

+ I just received her urinalysis and there is no reference range listed, but Googling seems to show that the Specific Gravity (1.03) is normal.

[Harley PoMMom]

+ I just received her urinalysis and there is no reference range listed, but Googling seems to show that the Specific Gravity (1.03) is normal.

Ok, let me get this correct, is her USG result listed as 1.030?

[PrincessDangers]

Ok, let me get this correct, is her USG result listed as 1.030?

Yes, that’s what the report says.

Her ultrasound and sterile urine sample tests (which I’m dreading on her behalf) are scheduled for Wednesday.

[Harley PoMMom]

Dog's with Cushing's rarely have an USG of 1.030, they drink gallons of water and pee rivers; Cushdogs have very diluted urine. So, based on everything posted about your precious girl, I really don't believe Cushing's is a likely diagnosis.

What do her teeth look like? Some dogs that need a dental cleaning will have an elevated ALP.

Hugs, Lori

[labblab]

I have to agree with Lori. The more you tell us, the less likely it seems that Cushing’s is the cause. I still think the ultrasound can be helpful in order to see if anything appears to be amiss with her internal organs. And again, the sterile urine sample can help to definitively rule out an infection.

But I do want to make sure that the vet would *not* be using this urine sample to perform the UC:CR analysis that we’ve been talking about. Although the ultrasound is not an invasive test, the vet visit will undoubtedly still be stressful for your girl and that would render the results of a UC:CR worthless. If you do decide to proceed with this test, you really need to gather the pooled urine sample yourself, at home, as calmly as possible. If your vet still wants to consider Cushing’s after the results of the ultrasound are in, though, I’d still strongly advocate for a UC:CR before advancing to the more involved and expensive blood testing.

Good luck on Wednesday, though, and we’ll be anxious to hear the results!
Marianne

[PrincessDangers]

Dog's with Cushing's rarely have an USG of 1.030, they drink gallons of water and pee rivers; Cushdogs have very diluted urine. So, based on everything posted about your precious girl, I really don't believe Cushing's is a likely diagnosis.

What do her teeth look like? Some dogs that need a dental cleaning will have an elevated ALP.

Hugs, Lori

Thank you both. Her teeth look great according to her vet.

I need clarification from the vet about the urine tests. I donÂ’t know why she didnÂ’t do the cortisol test with the last sample and I donÂ’t know what she hopes to get out of the sterile sample. ItÂ’s really hard having to wait hours or days for a returned phone call instead of having an in person conversation about such an important diagnosis.

[Harley PoMMom]

I need clarification from the vet about the urine tests. I donÂ’t know why she didnÂ’t do the cortisol test with the last sample and I donÂ’t know what she hopes to get out of the sterile sample.

The UC:CR test should be 3 morning pooled urine samples taken at home and then refrigerated until the samples can be taken to the vet's office. A sterile urine sample is performed so there is no concern of contamination of the sample from your dog's fur or genitalia, which often happens with a free catch sample and could otherwise interfere with or skew the results of the urine culture and sensitivity test.

I, too, am wishing you luck on Wednesday, please keep us informed!

Lori

[PrincessDangers]

The ultrasound was consistent with Cushing's, unfortunately. Her vet would like to move forward with testing and if that confirms it, she would like to medicate. My main hesitation is the follow up testing because she finds vet trips so stressful. That really complicates things.

They also found a large mass on her spleen (that is almost certainly benign) to remove. That could be irritating enough to be playing a role in the liver being agitated.

The vet isn't against running a UC:CR test, but she doesn't put enough weight in it to determine a diagnosis. She's inclined to test/start treatment for Cushing's Disease before addressing the spleen. I'm still thinking that through.

Thank you for all of your advice. I told her vet that I've been discussing it with you guys :)

[Harley PoMMom]

I would hold off on performing all tests for Cushing's until the mass on the spleen is removed. One of our Moderators, Leslie, had a precious girl, Squirt, who tested positive for Cushing's because of a mass on her spleen. The LDDS test, which is the "gold standard" test for Cushing's may yeild a false positive when a non-adrenal illness is present, such as the mass on your girl's spleen. Could you tell us exactly what the ultrasound showed? Also, I wanted you to be aware that chronic illnesses can enlarge the adrenal glands, just in case that was a finding on the ultrasound.

Hugs, Lori

[labblab]

Once again, I’m in 100% agreement with Lori. As she says, either of the two diagnostic Cushing’s blood tests can and do return “false positives” if a dog is suffering from some other illness or significant stress. Especially since your girl is exhibiting no observable symptoms consistent with Cushing’s aside from thirst/urination, I don’t understand why your vet would be prioritizing Cushing’s at all over and above the removal of the mass in her spleen. That mass may actually be the source of all the abnormalities as opposed to Cushing’s.

In honesty, if I were you, at this point I’d consider getting a second opinion about your dog’s entire situation before proceeding any further. In complicated situations, we often encourage folks to ask their vets for a referral to a veterinary internal medicine specialist in order to receive additional input. This is a vet who has received additional training in disorders such as Cushing’s, and can work alongside your current vet in sorting out the best path forward. We can help you search for a specialist like this if you’d like, but perhaps your current vet already knows of a specialty practice near you. From our experience here, though, we’d be wanting to see the issue with the spleen resolved prior to moving forward with any Cushing’s testing at all, even the UC:CR. Again, none of that testing may be accurate until the mass has been removed.

Marianne

[Squirt's Mom]

As Lori shared, my first dog diagnosed with Cushing's, Squirt, tested positive on the LDDS, HDDS, and ACTH. But when the ultrasound was done a tumor was found on her spleen. Once that tumor was removed and she had fully recovered all those test results returned to normal. The tumor had caused false positives. She also had very few signs. Had I started treatment instead of having the tumor removed the odds are she would have died either when the tumor ruptured or from the treatment itself because at that point in her life she did not have Cushing's.

My second dog diagnosed with Cushing's had COPD, anal gland disease, allergies, pouches on either side of her rectum that had to be manually emptied and other health issues. Her ACTH was too high to register - >50ug/dl. When she passed I had a necropsy (autopsy for animals) performed...it proved she never had Cushing's - her adrenal glands were normal. But like my first pup, all those other health issues caused the ACTH to register as if she did.

Cushing's is one of, if not THE, most difficult canine disease to correctly diagnose. Cortisol is a fight or flight hormone and it's job is to elevate naturally in response to any stress, internal or external. The tests for Cushing's can only tell us IF the cortisol is elevated but not WHY. For this reason it is very much a process of ruling out all other possible causes for the elevated cortisol. And you know there is another cause present with your sweet girl.

In your shoes I would insist the tumor be removed then give my baby plenty of time, a few months, to recover. Then, IF signs were present I would look at Cushing's again. But for now, Cushing's would be forgotten and I would focus on that tumor and her recovery. Just so you know what you would be looking for, here is a list of common signs seen with this disease:


*increased/excessive water consumption (polydipsia)
*increased/excessive urination (polyuria)
*urinary accidents in previously housetrained dogs
*increased/excessive appetite (polyphagia)
*sagging, bloated, pot-bellied appearance
*weight gain or its appearance, due to fat redistribution
*loss of muscle mass, giving the appearance of weight loss
*bony, skull-like appearance of head
*exercise intolerance, lethargy, general or hind-leg weakness
*excess panting
*seeking cool surfaces to rest on
*symmetrically thinning hair or baldness (alopecia) on torso
*other coat changes like dullness, dryness
*slow regrowth and/or failure to regrow of hair after clipping/shaving
*thin, wrinkled, fragile, and/or darkly pigmented skin
*thin, crepey, easily damaged skin that heals slowly
*dark, bruised looking skin
*hard, calcified lumps in the skin (calcinosis cutis)
*susceptibility to infections (especially skin and urinary)
*diabetes, pancreatitis, seizures

If, after she has had plenty of time to recover, you aren't seeing quite a few of these signs I would continue to watch and wait to see if she did develop signs. Cushing's is a very slowly progressing condition so there is rarely need to rush into diagnosis or treatment....especially when it is known that something is present that can and does cause false positives on all the tests for Cushing's AND that is much more pressing. :D

Hugs,
Leslie

[PrincessDangers]

Thank you.. That's how I feel as well.

Regarding the report, this is everything not-normal...

LIVER: the liver is large and diffusely hyperechoic-no focal masses or nodules are seen
SPLEEN: there is a large, complexly echogenic and mineralized mass effacing the body of the spleen and disrupting the capsule. The remaining spleen is within normal limits.
ADRENAL GLANDS: both are plump (caudal/cranial pole diams. = 0.75-1.4cm) and hyperechoic with decreaased internal architecture

CONCLUSIONS:
1. bilateral adrenomegaly + hepatomegaly: consistent with PDH-Cushing's syndrome
2. splenic mass: rule-out neoplasm, i.e. malignant vs, benign

RECOMMENDATIONS:
1. as needed for patient's well-being i.e. can consider aspiration samples from the splenic mass to try and confirm a diagnosis...vs. exploratory laparotomy for splenectomy
2. can test this patient for Cushing's disease and treat accordingly

When we were first discussing having an ultrasound performed, she had mentioned a list of things that might be causing the elevated ALP and the spleen was part of that list. After the ultrasound, I asked if the splenic mass might be irritating the liver and she said it is possible. I also asked if she would recommend treating Cushing's if the test is positive and she said yes. Seeing how stressed my pup was by the last vet trip, I wouldn't make that decision lightly. But the spleen has to come out regardless. That makes the most sense to me.

That stress is also causing me hesitation about bringing her to another hospital for surgery and an internist. We are about an hour away from the nearest good specialty hospital and 90 minutes from the two best internal medicine vets I know. I wonder if one of them would consider reviewing her case remotely?

[PrincessDangers]

Thanks, Squirt's Mom. This forum has been invaluable.

I definitely want to get that spleen out and reevaluate the diagnosis later on. I hope she is just like Squirt.

At the moment I'm debating between having her local vet pull that thing out or bringing her to a larger hospital. This local practice performed by other dog's spay surgery which included a ton of extra precautions (she only has one kidney) and I felt they did well. I wonder if laproscopic splenectomy is an option.

I love her so much and want to make the best decisions for her well-being but sometimes it doesn't seem straightforward.

She has some symptoms, but they're on the ambiguous side and could also have something to do with aging, the splenic mass, or arthritis (are all known conditions).

[PrincessDangers]

I've scheduled her splenectomy for next week.

I initially scheduled it at her local vet, but I had misunderstood and thought she would be coming home the evening of surgery. It turned out that she would have stayed at the hospital unattended overnight.

The specialty hospital an hour away was willing to schedule the surgical consultation and surgery for the same day (rather than dragging her back and forth for multiple visits). I hate to make her travel at all, but it just seems safer.

So, my plan is to let her recover from that and retest the ALP in six months or so.

Thank you all for your advice.

[labblab]

Oh, I’m so glad you shifted the surgery to the specialty hospital under these circumstances — I think that’s an excellent plan and I so hope that all goes well!

Definitely do update us just as soon as you are able to. Good luck, for sure!!!!

Marianne

[Squirt's Mom]

Sending prayers for you, your precious girl, and her medical team. Please keep us updated as you can. I fully understand how stressful the next week or so might be so don't feel pressured to chat with us...take care of her first and foremost. Just know we are with you every second.

Hugs,
Leslie

[PrincessDangers]

I don't have any pathology reports yet, so I have a few more days of apprehension, but surgery went well. They pulled a couple lipomas and a liver biopsy while they were in there. The surgeon said her liver looked fine, just plump/rounded. She suspects Cushing's is to blame too. I'm growing more skeptical of that.

I feel SO FORTUNATE that we had it done at this hospital vs. the local vet. They expected to release her on Thursday, but kept her for an extra night because she wasn't eating/drinking and just didn't seem bright. If she'd had surgery at our local doctor, I likely would have wound up at this other hospital anyway, transporting her while she was very uncomfortable, then trying to convince those doctors to admit her. Ugh. I was happy for her to have an additional day resting on heavy pain meds. The incision is her entire abdomen and she is extremely thin now. But she started wagging, drinking, eating, and being super affectionate as soon as she got home. My challenge now is just keeping her still.

Also, speaking with the surgeon, she said it could be anything from the most aggressive cancer to completely benign which further undermines my confidence in the primary care vet's direction to test for/treat Cushing's first. If it were the worst case scenario, why would she start such a long term treatment while she's, -at worst- ambiguously symptomatic with a time bomb in her spleen? We moved to our current home from NYC where we had easy access to multiple great hospitals, and prior to that my dogs went to UPenn. I think I took that for granted. Also, the other vet in the practice has given excellent care to my two other dogs (who are no walk in the park).

[labblab]

I'm sooooo relieved to hear that the surgery is safely behind you, and that you decided to have it done at the specialty hospital, too! I know that you still have the worry over the pathology hanging over your head, but thank goodness the surgery itself has gone well. And I have to hope and believe that the fact that she's actively happy now that she's recovering at home is a good sign, no matter what.

I'll be keeping all fingers crossed that the pathology report is a good one, that's for sure. And once we find that out, then we can plan out any further diagnostic steps in the days ahead. Thanks so much for letting us know how things are going!

Marianne

[PrincessDangers]

Thank you so much. I have partial results. The splenic mass was the most benign scenario. It would have eventually burst, so I'm lucky it was discovered and removed.

They sent her liver biopsy off for special stains, so I'm still waiting for those results. It looks like she might have some form of hepatitis (uncomfirmed), which might explain her increased ALP and take Cushing's off the table.

[labblab]

That’s wonderful news that the tumor was benign!! And you’re exactly right that it’s so lucky that it was discovered and removed at this stage. I’ve had two different friends now who have lost retrievers to burst splenic masses :-((((. There was no warning beforehand, and both dogs bled out before they could make it through surgery. So that ultrasound may very well have turned out to be a lifesaver for you guys.

Moving forward, it’ll sure be interesting to see how the diagnostics turn out re: the liver biopsy. So we’ll stay turned here for your next report, but so far — so good!

Marianne

[Squirt's Mom]

Great news on the splenic tumor! That was the same as for my Squirt. Because of that experience I always recommend the ultrasound if at all feasible. Praying the liver path report is just as good!