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 :D ). 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 :o

[ReggiesDad]

A little late on posting this but after two weeks of 40mg trilostane/day, he was slightly less ravenous and not getting up in the middle of the night to pee, but still drinking a lot and acting pretty hungry. Energy levels seem somewhat better and his skin and fur seem less dry. Post-trilostane ACTH stimulation test two weeks in came back 2.8 ug/dL pre, 8.6 post, while the internist said her targets for a dog being treated for Cushings were 1.5-3 pre, 4-6 post, so still a little high. We decided to up it to 60 mg/day, no signs whatsoever of cortisol dropping too low since then, maybe a minor further improvement in the eating and peeing but still not where I'd like it to be.

We're doing a pre-trilostane resting cortisol test two weeks out from the dosage change, so toward the end of this week. I'm thinking we may want to split the dosage and go twice a day. His drinking and appetite seem worst first thing in the morning.

[Harley PoMMom]

Thanks for the update! Glad you're seeing some improvements, however I'm a bit worried that the dosage was increased because it is recommended that no increase should be done until after the dog has been on Vetoryl for 30 days, the reason for this is that cortisol can continue to drift downward during the first 30 days of treatment.
Please do keep us updated and I do highly recommend that a full cortisol test be done since the dosage was increased.

Lori

[ReggiesDad]

Reggie's pre-trilostane resting cortisol was 2.8 ug/dL. He's been drinking and peeing a bit more lately (though less than before we started treatment) especially overnight and first thing in the morning, but otherwise seems to be progressing pretty well, still a little hungrier than I'd like but his energy and demeanor are notably better, his skin and coat are much less dry, and I think I'm already seeing the coat filling back in some (his fur is short enough that even a little fuzz makes a real difference).We're continuing 60mg once per day of vetoryl until the inital package runs out at the end of the month, then trying 30 mg twice a day.

[labblab]

Overall, I think this is a very good report. And I understand the notion of shifting to 30 mg. twice daily after you’ve finished the 60 mg, capsules. Twice daily dosing may be just the “tweak” you need to see sustained improvement. Thanks so much for continuing to update us, and we’ll definitely be interested in finding out whether the dosing change leads to even greater symptom resolution.

Marianne

[ReggiesDad]

So, I have a call in to my internist and will try to get ahold of my regular vet during working hours but:

Reggie (~50lbs) has been on 30mg Vetoryl twice a day for a few weeks now, "down" from 60mg once a day. Drinking and peeing seem better controlled, and appetite somewhat better controlled as well -- still generally quite hungry but has been letting me "sleep in" a bit more before breakfast -- shifting from ~4am to ~5am (versus he used to sleep until ~7am).

The evening of Tuesday 8/15 during our walk he found something on the sidewalk he ate before I could identify it. I suspect this is the cause of his subsequent digestive issues (see below) but I realize they are also consistent with the symptoms of overly suppressed cortisol. But would you expect to see that happen overnight several weeks in to a constant dosage regime?

Tuesday 8/15 his appetite was very fuil.

Around midnight the transition to Wednesday 8/16, he went out to poop (looked normal). Then he went out to poop again about an hour later (still normal, a little soft). And again multiple times the rest of the night, with very little coming out but still sniffing and squatting. At his usual breakfast time he wanted no food, but over the next couple hours he started accepting treats, then canned food, then kibble. We took a normal walk in the morning and he had a small but decently formed poop. He ate more kibble mid-day. Then around 4pm he threw up. Then he ate some canned food but refused kibble, took a good walk with some good poops, and seemed generally fine (but still not interested in kibble) until he threw up again at 9:30. He didn't seem to drink as much as usual in the morning, but drank at his recent normal level the rest of the day.

Around 3:30am Thursday 8/17, he threw up a very small amount, then went out and had a normal poop. As of 7am he ate a tiny treat and a spoonfull of canned food (all I offered him of that) with enthusiasm, but has no interest in kibble. Drinking normally.

So, I will follow my internist's advice, but as i wait to hear back...any thoughts on whether that the sudden onset of these symptoms is consistent with over-suppression, especially given the dietary indiscretion the night before?

[labblab]

I’m so sorry Reggie is feeling poorly and totally agree with checking in with your vet. However, on the face of what you’re describing, like you, I’m guessing it’s the dietary indiscretion that’s to blame as opposed to low cortisol. Having lived with and loved three Labs, I’m sadly quite familiar with the acute upsets associated with “garbage gut.” It’s truly amazing how quickly some of our dogs can spot and scarf up the nastiest of tidbits :-(.

However, it’s definitely good to consult with the vet. And if the acute symptoms continue or worsen, I’m guessing a cortisol check may still be recommended, just to be on the safe side. But hopefully you’ll be seeing improvement from this point on.

Marianne

[ReggiesDad]

Yes, thanks, that makes sense. I'm still waiting back to hear from the internist (and unfortunately she only works half days Thursday and not on Fridays or weekends, so it might be a while) but I was able to see my regular vet. She did some in-house bloodwork and based on his sodium-potassium ratio and a few other things does not think it's likely to be low cortisol. Unfortunately his ALP is even higher than the last time we checked, and for the first time his glucose is slightly above the reference range as well -- though she said that could be a response to stress.

Also, between when I posted the first message and when I saw my vet, he suddenly had blood in his urine. So we could be looking at a UTI as well, we sent out for urinalysis/culture but won't have results for that until tomorrow.

Edit to add: Heard back from the internist. She agrees this is unlikely to have anything to do with his cortisol being too low. However, she said it might be worth pausing the vetoryl until he felt better anyway, since this is the sort of event that should lead to elevated cortisol normally.

[ReggiesDad]

Quick update: Reggie's digestive upset had nothing to do with the trilostane, as we all suspected. He had a minor UTI that seems to have cleared up after some antibiotics. Progress on Cushing's treatment has not been great. His drinking and peeing are still abnormally high but tolerable and definitely better than pre-treatment. His appetite remains through the roof, he's continuing to put on a little weight, and he's remaining pretty lazy and recently lost some fur from his tail. This has been on 30 mg vetoryl twice a day. We just did a pre-trilostane blood draw yesterday, 4.0 ug/dL which is not super high, but higher than it was last time (2.8 both July 13 and June 27) or even his baseline in his LDDS test before we started treatment. So we're upping the vetoryl to 40 mg twice a day -- at his new weight of ~51 lbs that doesn't seem overly high.

[labblab]

Thanks so much for this update. I’m glad you’re seeing a bit of improvement with Reggie, but realize you still have a ways to go in terms of symptom relief. Coupled with the results of his cortisol test, I understand why you’re making the move to increase his dose. I really hope this will be a bigger step in the right direction. As always, good luck to you both, and please keep the updates coming.

Marianne

[ReggiesDad]

Thanks. If the 40mg dosage does seem to do the trick, I'm wondering what the latest group wisdom is on compounded trilostane versus branded Vetoryl. The internist I'm working with doesn't have strong feelings either way. Reggie has insurance, which helps quite a bit but doesn't fully cover the costs, so I do find myself wondering if spending around 4x as much for 30+10 mg of Vetoryl versus 40 mg compounded trilostane really makes sense in the long term.

[labblab]

Over our years here, I think there are few issues that have generated more discussion than the question of brandname meds vs. compounded alternatives. People have had, and probably continue to have, differing opinions. For what it’s worth, here are my own thoughts. I’ve certainly come to appreciate the fact that compounded trilostane can be a positive game-changer for folks, either because their dogs need doses that aren’t available in brand form, or because the high cost of Vetoryl would make treatment a huge financial burden. However, the downside is that compounded products are not inspected nor regulated in the same manner as FDA-approved pharmaceutical products, and some past studies have shown some dosage/efficacy irregularities in certain compounded trilostane products. So that remains somewhat of a worry to me. And for this reason, I think the reputation of any given compounder is especially important to investigate. On the thread below, we give people some tips in that regard:

https://www.k9cushings.com/forum/showthread.php?9066-Cost-Savings-for-Owners-of-Cushingoid-Dogs

Just as you have done with Reggie, my own personal preference would be to start off with brandname Vetoryl if the dose and cost is something my dog and I could handle. I would just have greater confidence about the consistency of the dose and efficacy. Once my dog became stabilized on a dose, that would be the time I’d feel more comfortable about trying a switch to a compounded version if the ongoing cost of Vetoryl is too burdensome since, at that point, I’d have the results of the Vetoryl with which to compare.

If you do end up sticking with Vetoryl, however, one other cost-saving possibility might be to give unequal twice daily doses. For instance, if Reggie hypothetically ultimately ended up with a 90 mg. daily total, one option might be to give one 60 mg. in the morning and one 30 mg. capsule in the evening. In a situation where the doses are unequal, the maker of Vetoryl recommends giving the larger dose of the two in the morning. Your internist might not be in favor of unequal dosing at all, and instead be more in favor of a compounded equal dose. But I just thought I’d mention it as yet one other option depending upon the total daily dose you ultimately end up with.

Marianne

[ReggiesDad]

Thanks, this makes sense. I brought up the idea of a 60/30 split with my internist, but her preference was equal doses. Still, especially if 40/40 doesn't quite seem to do the trick, I may bring it up again if this is the general dose range we settle on.

[Squirt's Mom]

Good to hear from you and good to hear the Reggie is showing some improvement. But, I also understand the increase and hope this does the trick for a bit.

As for compounded VS brand...you want to be sure the pharmacy is compounding using pure Trilostane, the active ingredient in Vetoryl. Some pharmacies have been using other products that are not pure Trilostane and the results aren't as positive. So just be sure what you are getting. ;) One pharmacy I feel good about recommending is CareFirst. I will give you a link below. They were more than happy to talk with the Admins of another group I work with so I would assume they would talk with his vet if desired. I use a quite a few compounded meds for my dogs and myself with no issues and they do save money.

Let us know how the increase works for your sweet boy!

Hugs,
Leslie

CareFirst:

https://www.cfspharmacy.pharmacy/

[ReggiesDad]

So Reggie has now been on his higher does of 40mg Vetoryl twice a day for a little over a month.

Frist the good news:
His drinking and urination seem to have improved a little bit more. It's at the point where I wouldn't consider it a major quality of life issue, although he still occasionally gets me up in the middle of the night to drink and/or pee. But he often makes it through the night, and then usually wants to eat breakfast before he goes out, so there's not a lot of urgency most mornings. Still it's clearly elevated compared to a healthy dog.
His appetite seems slightly more under control. He'll still complain if he doesn't get his usual amount of food by the end of the day, but he has gotten pickier with his kibble, sometimes waiting to see if he can score something better before eventually eating it. And his weight seems to have stabilized over the past month.

The bad news: His weight has stabilized at ~51-52 pounds. He's been as light as 38 lbs since I adopted him as a full-grown adult, and I think his ideal weight was 40-42 lbs, and that was with some pitbull musculature he doesn't really display any more. He still seems hungry a lot of the time, which can't be great for his quality of life and leads to some annoyance begging from me. Also he often is up and asking for breakfast by 4am and almost never sleeps past 5am -- he used to sleep in until I left for work in the morning (he comes with me, and would eat breakfast on the car ride in, or sometimes leave it to eat on the way home). Despite his weight gain, he seems to be losing significant muscle, and can't jump up on furniture like he used to. He rarely wants to walk very far, and is slow when he does. I'm not seeing further thinning of the fur on his flanks, and it might even be slightly filling back in, but his tail has started looking really ratty.

We did another pre-trilostane cortisol test yesterday morning. He was at 4.4 ug/dL, which my internist says is within the target range, and I understand that, but it also concerns me that Reggie's cortisol has never been particularly high, it just didn't suppress as it should, and he still shows pretty much all of the Cushing's symptoms other than calcinosis. His pre-trilostane cortisol was 4.0 ug/dL Sep 18, 2.8 ug/dL July 14, and his baseline at the start of his LDDS test on May 12 was 2.1 ug/dL.

So given that his cortisol is still trending up (though I realize there will be noise in any single measurement), he still displays significant symptoms, and shows no signs whatsoever of dangerously low cortisol, I am tempted to increase his dosage a little further. And/or I asked the internist if there was anyting else we might consider that might help with his energy levels and muscle mass/body composition. She said not really, at least if Cushing's is all he has going on. But she hasn't actually seen him in person in a long time (it's been a nurse taking the blood samples then we discuss via phone the next day), so she's going to look at him on Monday and re-assess.

Maybe I just need to be patient given that Reggie has shown a little bit of improvement lately, but it just seems like his quality of life isn't where it should be. But maybe he's just never going to respond much better than he has to date? If he was an old dog I'd be more willing to accept some of the deterioriation, but it's pretty hard to believe he's older than 9 at the absolute maximum (rescue so no way to know for sure).

[labblab]

I’m really glad to hear that your vet will be seeing Reggie personally on Monday. Given your description of his remaining clinical symptoms, I have to agree with you — my guess is that a medication increase may be in order. It’s true you’d be content with his pre-Vetoryl cortisol level of 4.4 as long as his clinical symptoms had resolved. But according to Dechra’s monitoring chart, a dog with a pre-pill cortisol level of 1.5 to 5.0 who continues to exhibit unresolved symptoms is a candidate for a dosage increase.

https://drive.google.com/file/d/1aQO-aek8tZHFyehNYAoW81hCSIpmiXNe/view?fbclid=IwAR194mX2KFv2SsptINmTmkzyRhb97IG87EeV Ak1ubAxplZWjCrdlG4CE7p0

Like you, I’d really hope to see more improvement for Reggie. So if I were you, I’d definitely want to discuss an increase on Monday.

Marianne

[Squirt's Mom]

One of the peculiarities of Vetoryl is that it isn't consistent across the dogs being treated with it. By that I mean one dog will do very well with a post # of 4 but another dog will be experiencing low cortisol symptoms at that level while a third dog needs an increase at that level because symptoms are not controlled. So Reggie may be one of those dogs who will do better, have better control, with a post most would consider getting dangerously low...closer to 2 than 4.

AND just to keep things interesting some dogs simply do not do well with Vetoryl and need to switch to Lysodren....and vice versa. Some dogs get very sick on any dose of Vetoryl but do very well with Lysodren....and vice versa. Some dogs get excellent control with Vetoryl but some are never controlled on Vetoryl and only find symptom relief with Lysodren....and vice versa.

Reggie is still in the very early stages of treatment so don't get discouraged just yet. Most of the time once that magic dose is found symptoms improve (with time) and folk find they have their old buddy back again. So just keep doing the great job you are so far and I am sure you will see the day when Reggie is feeling great and acting more like he used to. I have faith!

Hugs,
Leslie

[ReggiesDad]

The internist made note of Reggie having pretty much all the clinical signs of Cushing's (except perhaps the elevated cortisol itself) and no obvious signs of anything else. but still didn't want to increase his vetoryl dosage at this time. She did order a senior screen blood panel to see if there's anything else we're missing but it didn't seem particularly likely.

Meanwhile she did tell me one thing I hadn't heard before about why surgery for the pituitary version of Cushing's is so rare for dogs despite being fairly routine for people. She said that in addition to the obvious differences in how much people are typically willing to pay for treatment of a dog versus a person, human heads are remarkably consistent in their shape and layout whereas dog heads are anything but. So the procedure is more difficult and less standardized when it comes to dogs.

[ReggiesDad]

Some bloodowork results back. Back in May 2023, Reggie's T4 was at the low end of normal, but we didn't make too much of it because any of the potential symptoms of hypothyroidism he was showing were also consistent with Cushing's, and his appetite was so ravenous it seemed inconsistent with hypothyroidism. But now his T4 is very low, and this could explain a lot. The internist is waiting on a few more results before deciding how to treat the thyroid issues. This simltaneously feels like a real blow in terms of compounding multiple issues, but at least maybe it illuminates a path forward and insigt into why things weren't progressing as hoped.

[ReggiesDad]

Additional bloodwork shows TSH high-normal despite ~undetectably low T4, supporting a diagnosis of hypothyroidism on top of Cushing's, so were starting levothyroxine. Hopefully this is the missing piece to making Reggie feel better...

[Harley PoMMom]

Hope this works, keep us updated!

[ReggiesDad]

So it's been kind of a whirlwind with Reggie lately. It seems like we're making progress on the thyroid and Cushing's front, but there are new issues.

Reggie did perk up some in response to thyroid supplementation. Then a new crustly black bump showed up in his armpit, that rapidly grew to about the size of a pea and bled occaisonally. I set up an appointment with my regular vet to look at it and meanhwile asked my internist if Reggie was a candidate for surgery if surgical removal under anesthesia was recommended. She said not really. Meanwhile the day before my appointment, Reggie started having discharge dribble periodically out of his penis...not straight blood, not straight puss, but kind of a mix.

My vet ended up sick the day of our appointment, but I saw another great vet the next day. She wasn't too worried about the bump, which was very superficial, and said she could remove it under just local anesthesia if need be...though even then there might be some concern about Reggie's healing capacity given his Cushing's. The discharge was more of a concern/worry, she thought it pointed toward a prostate infection and recommended an ultrasound. His urine test showed no bacteria.

The next week we got an ultrasound with the internist, and she also looked at the discharge (which was continuing) under a microscope and clearly saw bacterial rods. His ultrasound showed cysts in his prostate, the discharge culture showed E coli, and the ultrasound also revealed a gallbladder mucocoel. Yikes! On the plus side, his weight had come down a bit, his cholesterol and electrolytes and liver enzymes were back in the reference ranges. But he was still showing all the classic outward signs of Cushings.

My internist said it was very rare in her experience for neutered dogs to have prostate infections unless they also had prostate cancer, and for that reason she was very esitant to go in with a needle to drain the cysts or inject antibiotic into them directly. And she was worried about the gallbladder mucocoel potentially developing into an emergence situtation, saying that in many dogs she'd recommend removing the gallbladder but Reggie really isn't a candidate for elective surgery unless/until we get his metabolism and hormones sorted (although even then, I'd probably lean toward letting him enjoy a healthier state than subject him to major surgery, but we'll cross that bridge when we come to it). To try to make him a better surgical candidate/hope to better control his Cushing's, we upped his Vetoryl to 60 mg twice a day and also bumped his levo-thyorxine slightly. We also put him on enrofloxacin for the prostate and ursodiol for the gallbladder.

And fingers crossed but....it seems to be working some! He still has a big belly, but has lost a little more weight, his drinking and peeing are almost normal, and he still won't walk very far but he's actually run and played a little bit lately, and is having an easier time jumping onto furniture. In his followup ultrasound today the prostate cysts had shrunk by ~75% so we'll keep up the anitibiotic for a while, and the gallbladder looks stable.

Oh yeah...meanwhile the armpit bump just fell of one day. Problem solved?

[labblab]

And fingers crossed but....it seems to be working some! He still has a big belly, but has lost a little more weight, his drinking and peeing are almost normal, and he still won't walk very far but he's actually run and played a little bit lately, and is having an easier time jumping onto furniture. In his followup ultrasound today the prostate cysts had shrunk by ~75% so we'll keep up the anitibiotic for a while, and the gallbladder looks stable.

Omigosh, all my fingers *and* toes are crossed for Reggie, too! After reading about his new challenges, I was sooooo relieved to get to that paragraph, and will definitely be hoping that things keep improving for your sweet boy. You are doing such a great job of advocating for him, and thank goodness you have access to this specialized medical care on his behalf.

As always, thanks so very much for this update, and I send all my best wishes for even more good news to kick off 2024!

Marianne

[ReggiesDad]

Almost exactly a year after his tentative diagnosis, Reggie is doing great now that we have dialed in the treatment for his Cushings (60 mg vetoryl twice a day) AND his hypothyrodism (0.6mg levo-thyroxine twice a day) AND his diabetes (9 units Humulin N U-100 twice a day). And the ursodiol seems to be keeping his gallbladder issues in check. Thank goodness for insurance!

Here he is near the peak of Cushing's symptoms, 52 lbs with almost no fur on his underside and thinning other places:
https://www.k9cushings.com/forum/attachment.php?attachmentid=8875&d=1716431461

And here he is now, 38 lbs with more and thicker fur than he had when I first adopted him 4.5 years ago:
https://www.k9cushings.com/forum/attachment.php?attachmentid=8876&d=1716431480

He's back to jumping on furntiture, playful bursts of energy, and moderately long walks every now and then and consistently taking at least short walks.

[Joan2517]

What a wonderful update! He looks gorgeous!

[Harley PoMMom]

What a transformation, he looks so good!! What a wonderful job you are doing!!!!!

[labblab]

I totally agree -- what a great report and what a lovely photo :-))))))))

Your experience with Reggie just goes to show that there can be a lot of variability with successful Vetoryl dosing. We might think that 60 mg. twice daily is a lot of medication for a 40 pound dog, but clearly he is thriving right now on his current treatment regimen. You've had a lot to handle on his behalf, and you've managed it beautifully. Thanks so much for treating us with this wonderful update!

Marianne

[ReggiesDad]

So...in his latest bloodwork Reggie's pre-trilostane cortisol was 1.5 ug/dl which I understood to be the lower bound of the target range. Our internist was somewhat conserned about that and watned to test his electrolytes and some further bloodwork as well. His blood sugar (non-fasted) was still quite high (477), liver enzymes all normal, low sodium and high potassium (didn't get the numbers). So she wants to up his insulin a bit but is also worried we have been over-suppressing his cortisol so she wants me to stop the vetoryl for a week and re-test.

I'll follow this advice but it's tough. He's not showing any signs of being clinically unwell other than his drinking and urination still being a bit elevated compared to a healthy dog. And even if this treatment is doing long-term damage to his adrenal glands, his quality of life seems so much better than it was when he was on a lower trilostane dose, even if he is being over-suppressed, the tradeoffs could well be worth it. And his very first baseline cortisol measure before starting any kind of treatemnt was only 2.1 ug/dl, Hmmm...

[Harley PoMMom]

What is his post ACTH stimulation result? If the post was on the lower side also I agree with the vet on stopping the Vetoryl. If cortisol is too low it can be fatal if not corrected. Too low cortisol, called Addison, can cause increased drinking and urinating.

[ReggiesDad]

Thanks for the reply. Rehhie has not had an ACTH stimulation test, this decision to cut off the vetoryl was based only on his pre-trilostane cortisol level and his electrolytes and maybe also his urinalysis which she said showed his urine was highly concentrated but otherwise unremarkable.

[labblab]

Gosh, I understand how conflicted you must be about taking the break from the Vetoryl. But I’m guessing that the electrolyte imbalance is the piece that is really helping to fuel your vet’s concern. We already may have talked about this earlier, but in addition to lowering cortisol, Vetoryl has the capacity to also lower aldosterone. And that’s the adrenal hormone that controls the potassium/sodium balance. Vetoryl’s manufacturer specifically warns that the med should be discontinued if cortisol drops too low and/OR an electrolyte imbalance is seen. So even though Reggie’s cortsol level remains on the lower boundary, his aldosterone may truly be too low if it were to be measured.

So as frustrating as it is, I think your vet is doing the right thing since elevated potassium can truly be life-threatening due its potential effect on the heart. Hopefully the week “off” will help stabilize Reggie’s readings, though, and clarify the best path forward.

Sending positive well wishes to you both,
Marianne

[ReggiesDad]

After a week off vetoryl, Reggie's cortisol rebounded to ~4.7 and his electrolytes are normal. So, looks like no lasting damage from potential over-treatment. He's also got borderline too much appetite, is urinating very copiously, and panting more than I'd expect although we are having a little warm spell. So we're resuming treatment, 50 mg twice a day for a month and then rechecking. I have enough 30 and 10 mg tablets on hand from earlier treaments to start out using them to add up to 50, but we are also going to see how he does on Chewy's 50mg compounded trilostane.

[labblab]

OK, sounds like a plan! I’m so relieved that Reggie is stable again at this point, and will surely be hoping that this turns out to be the optimal dose for him going forward. As always, we’ll be watching for your next update!

Marianne

[ReggiesDad]

So, externally Reggie was doing quite well on 50mg of Chewy-compounded trilostane twice a day. But while his latest bloodwork was fine for electrolytes, his cortisol was slightly lower than when our internist wanted to discontinue the 60mg. So she wants to take another week break and then try out 40mg twice a day. I guess after the last trilostane "break" this one is easier for me to accept as a good idea, Reggie's symptoms definitely came back during his last break but then cleared up just as quickly once he was back on the medications.

Meanwhile he's got hints of cataracts in both eyes, we're doing the best we can with his diabetes and blood sugar management but so many moving parts at the moment... There is no obvious effect on his vision and his opthamologist started him on Ketoroloac to hopefully prevent any inflammation. It doesn't seem like we need to be considering surgery "yet" but the thought of three weeks in a cone is kind of a bummer...

[labblab]

I definitely understand your dread of the cone. I personally had my own cataracts removed last summer, and even though there was no cone for me, I sure got tired of all the eyedrops, eyedrops, eyedrops I had to take!

I’m really glad to hear that, otherwise, Reggie has outwardly been doing well. Under these circumstances, I’m sorry that you’ve got to tweak the trilostane once again. But it really does sound as though that’s the safest route to go if his cortisol is heading back down.

Keep up the good work, Dad. Reggie is so lucky to have you, and we’re always so glad to get your reports!

Marianne