Reggie, an 8-ish pit mix who may have Cushing's and/or other issues

[ReggiesDad]

Reggie is a rescue pit bull mix. Probably about 8 years old (could be as young as 6, might be 9). According to his DNA test, he is 3/8 American Staffordshire, 1/4 assorted breed groups (terrier/sporting/herding -- out of these I think I see chocolate lab traits), 1/8 pug, 1/8 Pekingese, and 1/8 Shih tzu. When he was in better shape, he was 40-42 lbs (currently 47). To get to the TLDR bottom line up front: My primary care vet thinks Cushing's is plausible but not definitive, even if he has Cushing's there is probably at least one other concurrent issue, and we'll be seeing an internist May 31 to figure out next steps. But I'd love any insights on what to be thinking about / asking of the internist / considering if starting treatment is an option. Im particularly interested in how likely people think treating for Cushing's is to improve activity/energy levels in a dog who used to be a great hiking companion but now mostly wants short and slow walks, sometimes only just far enough to poop.

Reggie had a rough life prior to adoption 4 years ago, living with a mentally unstable homeless person who was in and out of jail, sending Reggie in and out of the shelter. He eventually got shipped to another town to break the cycle. He had some skin problems that resolved pretty quickly, otherwise he seemed to be in pretty good health (although I suspect his diet was terrible on the streets). He did have an extended bout of colitis, gut noises, and loss of appetite/lethargy in spring of 2021, but the colitis cleared up after starting metronidazole and the gut noises and appetite issues resolved after switching to prescription high-fiber kibble.

Starting the the fall of 2022, he started getting less enthusiastic about walks, though it was hard to separate a lack of energy or discomfort from a reaction to the changing weather (he's a California dog, so not used to cold weather or rain except in the wintertime -- and this past winter was a doozy). He also seemed to be getting a little hungrier and more demanding of treats, but again maybe that was just a reaction to the colder weather. His urine volume seemed to increase a bit, but that was hard to separate out from holding it in longer since he was going out less.

I took him to my vet in January 2023 wondering if he might be hypothyroid and/or have some joint or muscular issue causing him discomfort that could explain the lower energy. An orthopedic exam turned up nothing, and his bloodwork was largely unremarkable (but see below for hints consistent with Cushings) aside from elevated cholesterol. T4 was toward the low end of normal but he didn't really show other symptoms of hypothyroidism so we didn't make much of that possibility.

Thinking he didn't have any physical issues to prevent him walking, I pushed him a little more to take longer walks and he seemed to be doing ok activity-wise, especially given the ongoing poor weather. But as things still didn't improve into the spring of 2023, and especially as he looked less comfortable when he did walk a decent distance, I took him back to the vet. We considered that he might have a back injury, but decided to wait on X-rays under anesthesia and instead try carprofen to see if that improved things.

I don't think the carprofen helped much. And after just over two weeks on it, he started having streaks or spots of fresh red blood on well-formed stools. Which doesn't really seem consistent with the kind of upper GI upset you'd expect on carprofen, but the timing was quite odd. Combined with some further elevation of his liver enzymes on the 2-week blood test, we chose to discontinue the carprofen. (This might have helped with the bloody stools which have become less frequent [so far we're only about a week out from discontinuing the carprofen, so probably not completely out of his system] but still concerning, so we will be checking with the internist about that as well.)

The liver enzymes and careful thought about other changes and signs had us thinking more about Cushing's, so we did a low dose dexamethasone suppression test. He showed the "escape" pattern that is consistent with, but not very definitive for, pituitary-dependent hyperadrenocorticism. His baseline cortisol was not unusually high (2.1 ug/dL w/ reference range 1.0-6.0). My vet wants me to check with an internist before starting treatment, which I think makes sense, especially given the potential for alternative or concurrent issues.

Unfortunately, we can't see the internist for another 11 days. I'm hoping to have a lot more clarity after that, but in the meantime if anyone has thoughts on alternate explanations we should be thinking about, or how soon to start on treatment if this is indeed the early stages of Cushing's, would be most welcome.

The gory details:

Main Quality of Life Concerns
Low energy/enthusiasm
*Lost any interest in toys over past ~18 months
*Much less enthusiastic about walks since ~fall/winter 2022
*Less excited to see friends, visit favorite parks, or even lie outside in the sun
Signs of possible pain
*Looks fine when moving at a trot, but...
*When doing "long" walk, often appears stiff after some distance
*No single limb consistently favored, but some signs of left shoulder hitch
*Back legs wobble when tired or going up hills (has cow hock)
*Sometimes one limb will shake -- not consistent, more often one of rear limbs
*Lazy sit (has had this to a large extent since I first adopted him)
*But, no obvious improvement on ~3 weeks of vetprofen
**And, moves quite well getting around the house, or on most short walks
**Jumps on furniture easily, often but not always uses stairs to get off
**Gets up from sitting/lying easily
Appetite
*Hungry all the time (while gaining weight), whines for food/treats
*Wants to eat first thing in morning (used to sleep in if I let him)
*Will happily and hungrily eat plain kibble, used to let it sit until really hungry
Drinking/urination
*Increasing, but not really a problem yet (see below)

Other issues/ symptoms
Blood in stool
*Fresh, red blood on well-formed stools
*Sometimes smear, sometimes spots
*First noticed after ~ 2 weeks on vetprofen
**Somewhat intermittent (at least not obvious)
**Less common since discontinuing vetprofen
*Occasionally accompanied by traces of mucus
Occasional minor gut noises, especially in mid-May
Period of increased flatulence in mid-May
Possible swallowing of reflux
*Sometimes, especially in evening, will spontaneously snap teeth and smack lips
**[does not seem like a seizure]
Increased drinking and urination
*Drinks more than he used to, though not as much as my last dog when he was on long-term prednisone treatment
*More frequent and larger volume of urine
**But no accidents, usually wants to eat before going out in morning
**Pretty solid yellow color
Thinning of fur on flanks, underside
Dandruff
Potbelly
Possibly less power in hind legs?
*Was having harder time jumping into car, but still easily jumped on furniture, heavier
*In past month I have been making him let me pick him up to get in/out of car, he seems able to do it if allowed
Crusty nose, paw pads (consistent since adoption)
Many skin bumps - some spontaneously resolve or peak then shrink (ongoing since adoption)


Notable bloodwork results

Jan 23 2021:
ALT 17 U/L [reference range 18-21], ALP 25 [ref. 5-160], AST 19 [16-55]
T4 2.4 ug/dL [ref. 1-4]

Jan 26 2023:
WBC 4.0 K/uL [4.9-17.6]
MCH 26.7 pg [21.9-26.1]
LYMPHOCYTE 548 /uL [1060-4950]
EOSINOPHIL 40 /uL [70-1490]
T4 1.2 ug/dL [ref. 1-4]
ALT 63 U/L [ref. 18-121] ALP 210 U/L [ref. 5-160], AST 23 [16-55]
CHOLESTEROL 564 mg/dL [ref. 131-345, was 276 in Jan 2021] (note: non-fasted)
GLUCOSE 96 mg/dL [63-114] (note: non-fasted)

May 2 2023 [after 13 days of Vetprofen]:
CREA 0.4 mg/dL [ref. range 0.5-1.8, was 0.6 Jan 2021], BUN 14 [ref. range 7-27]
ALT 161 U/L [ref range 10-125], AST 42 [0-50], ALKP 372 [23-212]

May 12, 2023
Dexamethasone Suppression, Low Dose (One Pre, Two Posts)
Baseline cortisol 2.1 ug/dL [ref. 1.0-6.0]
4 hr post-dex cortisol 0.8 ug/dL
8 hr post-dex cortisol 1.6 ug/dL
"may support a diagnosis of pituitary-dependent hyperadrenocorticism"

Fecal parasite test
5/8/23 negative visual ova&parasites, Giardia, hookworm, whipworm, and roundworm antigens

Past problems that seem to have resolved
Loose, bloody, mucusy stools accompanied by gut noises and lack of appetite: spring 2021
*blood/mucus resolved shortly after starting metronidazole
*gut noises and appetite resolved after starting high fiber prescription diet

Reggie's Current Medication
No prescription drugs currently
On Heartgard, NexGard

Reggie's Past Medication
Vetprofen 75mg daily (split into two doses) 4/19/23-5/10/23
*stopped due to bloody stools, liver enzymes in bloodwork, lack of obvious effect
Metronidazole 250 mg daily 2/16/21-7/6/21, then phased out with last dose 7/21/21
*stopped due to colitis, gut noises, and lack of appetite resolving
Fluoxetine 20mg daily 2/2/21-6/17/21, then phases out with last dose 7/30/21
*stopped due to lack of signs of anxiety (was a hypothesized cause of colitis)

Food/Supplements/Treats
Purina Pro Plan Veterinary Diets EN Gastroenteric Fiber Balance Dry Dog Food
Purina calming care probiotic
Pawstruck glucosamine/chondroitin chews
Greenies dental chews
Dog Chits lamb lung
Pawstruck Beef esophagus strips
Freeze-dried beef liver
Blue Buffalo Nudges Chicken/Duck jerky
[Discontinued: had been giving him occasional raw or smoked cow femurs through mid-May]

[labblab]

Welcome to you and Reggie — we’re so glad you’ve joined us. Without doubt, you are Reggie’s hero in shining armor! After his tough early years, you are taking such very good care of him in his forever home. He’s a very lucky boy to have you for a dad!

Unfortunately, I don’t have a lot of time to write this morning, but I’ll definitely return later on today to offer some thoughts. At first blush, I do think Cushing’s is a possibility. But I’ll reread your thread once again more carefully before replying. You’ve done a great job of supplying us with so much very important information! So I’ll be back, and once again, a big welcome to both you boys :-).

Marianne

[Squirt's Mom]

Hi Dad and welcome to you and Reggie!

I did a quick read of your post and while many things, signs and some of the labs, are indicative of Cushing's there is LOTS of room for other diagnoses as well. In your shoes, I would concentrate first on everything else and set Cushing's to side. Here is why...

Cushing's is one of, if not THE, most difficult canine disease to correctly diagnose. This is partially because the signs for Cushing's are not unique to Cushing's - they are shared by many other diseases like liver and kidney disease, diabetes melletus, diabetes insipidus to name a few. In addition, NONE of the tests for Cushing's are conclusive. A diagnosis of Cushing's requires a thorough ruling out of any other possible cause (and sweet Reggie has several - digestive for example) and tests that were performed as accurately as possible. In Reggie's case, as was the case with both my cush pups, there were other things going on when the LDDS was run. The LDDS is notorious for false-positives if any other health issue is present at the time of the test. One of mine had a tumor on her spleen, the other had a host of issues including colitis. The one with the tumor tested positive on the LDDS, HDDS, ACTH, and UTK panel but the ultrasound found the tumor. Once it was removed all those tests returned to normal. Cortisol will rise NATURALLY in the face of any stressor...that is it's job so it can help the body cope during stressful times/events. The tests for Cushing's can only tell us if the cortisol is high but they cannot tell us why it is high. So I would ask the IMS to look at every other possible cause for the things you are seeing in your sweet boy and the abnormalities on the lab work. FYI...the abnormalities posted are mild compared to many cush pups we see so I wouldn't worry overly much about that currently. Not at all uncommon to see the ALP in the 1000's.

One thing did jump out at me and sort of took my breath away...the lip smacking and snapping at the air ( called "fly biting")...and it is always difficult to mention but I do want you to be aware. This behavior can indicate something as mild as digestive upset and as serious as a brain tumor. With the ***possibility*** of a diagnosis of PDH (the pituitary form of Cushing's - Pituitary Dependent Hyperadrenocortism) this also means there is a ***possibility*** of a macroadenoma or macro for short. These are the pituitary tumors that grow beyond the usual size for a PDH pup. Most of those tumors remain microscopic, causing nothing more than the typical signs of Cushing's and are easily managed with medication. In rare cases tho, that tumor starts to grow causing neurological signs...lip smacking and fly biting are among those signs. So in your shoes one of the first things I would want, if feasible, is a scan of the brain to see if a macro is present, or other tumor (we all, including docs, tend to get tunnel vision with Cushing's thinking EVERYTHING is related ). This is more common in the smush-faced dogs like Boxers but not knowing his head shape and with the genetics of Peke and Pug it is worth a peek to me.

Now that I have muddied the waters for you I want you to know how happy I am that you found us. I look forward to learning more about your precious baby boy as time passes. And thank you for saving his life and showing him what having a real home filled with love is all about.

Hugs,
Leslie

[labblab]

OK, I’ve made it back again, and I’m so glad to see that Leslie has also now had the chance to talk with you. Like both of you, I think it’s an excellent idea to have further evaluation done by the internist. Reggie’s history and overall clinical picture could indeed signal a combination of underlying issues that could benefit from attention. But after reviewing your thread once again, it still seems to me that Cushing’s may be a strong contender. A number of his outward symptoms and lab abnormalities are consistent with the disease. I won’t bother to list them all because you’ve already provided such a thorough summary. But obviously the increase in appetite/thirst/urination, thinning coat, muscle weakness, exercise intolerance, and skin issues are right at the top of the list of observable problems. Among Reggie’s other outward symptoms, a couple more especially caught my eye simply because they parallel my experience with my own Cushpup. My boy also had an unusually crusty nose which we could never explain. Additionally he too suffered from recurrent episodes of bloody colitis for which our internist never identified a specific explanation other than just overall gastric irritation from his highly elevated cortisol. Finally, you mention that Reggie is no longer interested in lying in the sun. Cushpups can become dramatically heat intolerant. Prior to treatment, my boy would end up abandoning us in the family room to go off to be by himself on the cool hardwood floor of our foyer. This behavior was so unusual for him and was one of our first clues that something was very wrong.

In addition to the outward symptoms, Reggie exhibits elevated ALKP, ALT, and cholesterol. At the same time, he has a decreased level of lymphocytes and eosinophils which can also be found in dogs with Cushing’s. And of course, the LDDS results are also consistent with Cushing’s although his 8-hour level looks to be only slightly elevated into the diagnostic range.

As far as the teeth snapping and lick licking, Leslie is certainly right that there can be a neurological component here. I had a non-Cushing’s Lab girl who developed grand mal seizures of unexplained origin several years after first exhibiting odd fleeting episodes of biting in the air and we’ve always assumed that they were likely a precursor. But I’ve also read that snapping and lip-licking can be caused by gastric issues, which my girl also suffered from. So that snapping behavior may have been totally unrelated to her future major seizures. That may be the case for Reggie, too. As Leslie says, it would require imaging of the head to search for the presence of a pituitary tumor or other brain issues. Unfortunately, that imaging can be quite expense and that’s why we never had it done ourselves.

All in all, I’ll head back full circle to repeat that I definitely agree the visit with the internist is a very good idea. He/she may have other diagnostics that may be recommended. For instance, there’s a second diagnostic blood test that the IMS may be interested in: an ACTH stimulation test. This test only takes an hour to perform as opposed to the 8 hours for the LDDS. The ACTH is known to return more “false negatives” than does the LDDS. But if Reggie were to have a positive result on the ACTH as well, that could add to the confidence of the diagnosis. Also, an abdominal ultrasound is often requested in conjunction with a Cushing’s diagnosis. It can provide very helpful visual information about the status of the adrenal glands and other internal organs such as the liver, kidneys, gallbladder and spleen. Also, I’m thinking the specialist may be able to draw some conclusions about the crusty nose and skin bumps. Maybe a fungal infection? Maybe something else? For instance there’s a specific type of skin plaque that can develop in dogs with Cushing’s, and the internist may be able to recognize that immediately if it is present. If so, that’s virtually a definite confirmation that Cushing’s is present and is the cause of the skin lesions. So I think we’ll all have more to go on after you’ve seen the internist.

I know I haven’t yet addressed your treatment questions in the event that Cushing’s does seem likely, but we can talk about those in another post ;-). In the meantime, please continue to ask any more questions that come to mind.

Marianne

[ReggiesDad]

Thanks for the welcomes and thoughts. I'll definitely keep you posted on what we learn from the internist. The lip smacking seems somewhat different from the fly-biting seizure videos I've seen online (not to mention different from the major seizures my last dog toward the end of his life), but that had occurred to me. It does seem to only happen when he's lying down, and either asleep or at least drifting off to sleep.

[ReggiesDad]

Just a quick update for now. We saw the internist, she also suspects Cushing's but is not entirely convinced, calling the LDDS results pretty marginal. She took blood for a single sample bile acid test, I don't have the numbers on that but she said it showed no signs of problems with liver function and ruled out some worse options.

She wasn't terribly concerned at this time about the bloody stools (which seem to be getting better, but things have seemed to clear up for a few days in the past only to show up again) or the lip smacking (which he also displayed briefly last summer, I should have mentioned that in my earlier post, it spontaneously resolved) and suspects both could be from exacerbation of his past dysbiosis (her diagnosis for his colitis in 2021). We have an abdominal ultrasound scheduled for June 6 to figure out next steps, meanwhile he's on metronidazole for the suspected dysbiosis.

His energy levels are maybe slightly better lately, but he's acting even hungrier and seems to be drinking and urinating even more.

[Harley PoMMom]

Thanks for the update, we really appreciate it! We will be looking forward to seeing the ultrasound results, and good luck!!

Lori

[ReggiesDad]

We had the ultrasound today. Both adrenal glands are enlarged, and the internist said his liver looks like the liver of a dog with Cushing's. Not sure if that means she has some gestalt for what the livers of Cushing's dogs tend to look like, or just that it doesn't look consistent with some sort of alternative liver disease diagnosis.

So we're starting on trilostane, 40mg/day (so a little less than 2 mg/kg given he's ~48 lbs now). She said it could take months to show much effect, starting with the drinking/peeing, and then hopefully things like his appetite, energy level, and fur improving after that. I've heard of some dogs responding a lot faster though, so not sure what to expect in terms of timing.

Will return in 2 weeks for ACTH test to adjust dosage if needed.

[Harley PoMMom]

Improvements in eating and drinking are generally seen within two weeks, hair regrowth can take up to 6 months. Just make sure you keep an eye out for cortisol dropping too low which are vomiting, nausea, diarrhea, or Reggie just not acting himself, if any one of these symptoms are seen than stopping the Vetoryl is required. Also, it is recommended that no dosage increase be done until the 30 day mark because cortisol can continue to drift downward during the first 30 days of treatment.

Please keep us updated!!

Hugs, Lori

[Squirt's Mom]

i want to reiterate what Lori has said about watching CLOSELY for those signs of overdose/cortisol dropping too low. He has two risk factors for this in my mind...questionable diagnosis and starting dose is too high. So please watch for those signs and if you see ANY of them stop the Vetoryl immediately.

And do please stay in close touch with us these first 30 days of treatment.
Hugs,
Leslie, the worry wart