My shiapoo Cooper and I are new to this forum

[charley]

I hope I am posting my introductory message correctly.

I have been very distressed since my 10 year old shiapoo had a splenic mass removed in March 2014. We thought he was just gaining weight in his abdomen but then it started to take a strange shape and turned out to be a low grade sarcoma. Although it appears to have been completely excised, there is the risk of it returning and I plan to address that.

The problem is that before the cancer confirmation came back he was also diagnosed with pituitary dependent cushings. The doctor started him on trilostane at 20 mg daily and when that looked like it was killing him and he would not eat, the doctor dropped it to 10 mg daily.

When we were at an appointment with a veterinary cancer group, he collapsed. Luckily, next door, was the emergency care group. His blood glucose was over 750 and his heart rate was 40. He had pancreatitis and a UTI infection. So, at that point, a new internal medicine doctor from this organization stepped in to try to get Cooper's blood sugar down by prescribing humulin n insulin. He would respond and then he wouldn't. We got up to 10 units for a 18 pound dog and she told me that we needed to start mitotane to get his diabetes under control.

I am so confused at this point. I finally went to another doctor who had been involved in the u.s. with the surgical removal of the pituitary tumor in dogs. He told me that Cooper was not a candidate because he is not showing any neurological signs and because of his low grade sarcoma. So, he decided to start Cooper on 10 mg twice a day of trilostane. It wasn't more than a week and he was the walking dead again, wasting away, not eating, etc. So, we dropped to 5 mg twice per day. But, the catch is that it had to be compounded because the smallest Vetoryl dose is 10 mg. (I'm not quite sure why that is.)

After another week of the 5 mg compounded trilostane dose, I really thought he was going to die. Since his insulin had been reduced to 5 units, his blood glucose was basically between 683 and over 750. I told him I wanted to stop the trilostane and get the diabetes under control with a different type of insulin. I said this because at an earlier meeting he said he preferred a different insulin when the dog has diabetes and cushings. So, I stopped the trilostane, and after a couple of days he's eating and has some energy. Of course his blood glucose is 722. I'm hoping that stopping this compounded trilostane will stop the muscle wasting and shaking eventually too.

Can someone please tell me if they have had any of these experiences? I don't know what to treat first. I want to save my dog and I'm willing to do whatever it takes to keep him alive but only if he has a good quality of life. Can you please tell me also what you think about this regime that their oncologist is going to try to tell me about that works to prevent the cancer but maybe can reduce the size of the pituitary.

Also, since this is a complex case, if you can recommend any specialists in the Los Angeles area, or even in California, I would love to know about them. I've been all over the internet and I just need some clarification.

Thanks so much!

Charley

[labblab]

Hi Charley, welcome to you and Cooper! I apologize by starting off with a question, but by any chance, are you currently consulting with Dr. David Bruyette there in Los Angeles? If so, I think you are receiving the most up-to-date and advanced treatment information that is likely available. Another forum member was the first dog to undergo the then-experimental pituitary surgery under Dr. Bruyette's direction. And for a short time, Dr. B was also an active member fielding questions here.

In terms of diabetic control, we do have a sister forum wherein you can discuss your insulin questions in greater detail. Here's a link:

http://www.k9diabetes.com/forum/

Sorry I only have time right now for this brief welcome to you, but from your intro, I did want to first double-check with you about Dr. Bruyette. If you are not already seeing him, he would be a great resource and I can return and give you his contact info.

Marianne

[charley]

Hi Marianne.

Thanks for your welcome.

Yes we are currently with Dr. Bruyette. I finally got to him after being with two other internal medicine physicians that I did not think were on the same page as me.

It is good to hear that you believe he is a source of information. I reviewed his background for quite a while before I went with him. He said that the surgery is not an option so that was disappointing. Since this case also involves cancer and diabetes, I wanted to know what other people's experiences had been. We've had terrible experiences with trilostane and he says that mitotane is not an option either. Basically, I think he wants to do chemotherapy.

I would love to know if others have gone down this road. Or, if they can recommend anyone else to get a second and third opinion.

Also, do you know how that other forum member's pituitary surgery went and if anyone else is doing this surgery?

I would appreciate any advice.

[labblab]

Hi again, Charley.

The member's dog who underwent the surgery was known to be suffering from an enlarged macroadenoma that was indeed causing neurological issues. Lucy's surgery was a success, but she later ended up passing from an unrelated problem. There are a few other treatment centers/approaches that are tackling newly developing pituitary intervention in the U.S., but my understanding is that the treatment (surgery or radiation) is still largely reserved for dogs with known macrotumors. Imaging of the head (CT or MRI) is required to make this diagnosis.

I know you are in good hands with Dr. Bruyette. But here are some additional questions that will bring us up to speed. You say that the Cushing's diagnosis preceded the discovery of cancer (and preceded diabetes, too?). Can you give us a timeframe, and also tell us about the symptoms that prompted the testing for Cushing's? Has Dr. Bruyette expressed any doubt as to the validity of the Cushing's diagnosis? Like, for instance, might the as yet undiscovered cancer have been responsible for any symptoms or testing abnormalities?

Also, it is true that when diabetes precedes or accompanies a Cushing's diagnosis, it is often preferable to try to first control the diabetes so as to see whether the Cushing's may be a false finding. So that's why the diagnostic timing and symptom development is of interest.

Last but not least, can you describe for us the oncology treatment that is being proposed? Is this a medication or instead some other type of intervention?

Thanks in advance for all this information.
Marianne

[charley]

Thanks so much for your reply and your questions.

When the spleen and splenic tumor were removed in March 2014, the surgeon stated that she was concerned that Cooper may have Cushings because he had elevated alkaline phosphatase on the chemistry panel, which was 749. They also noticed his distended abdomen and that both his left and right adrenal glands were palpably enlarged, his liver was enlarged, and that he had a high glucose reading.

I followed up with my primary vet and had the Low Dose Dexamethasone and High Dose Dexamethasone testing done, which indicated consistency with pituitary dependent cushings. I have also had an MRI of his brain done, which did reveal a pituitary macroadenoma.

I then pursued obtaining a third opinion of the splenic mass and omentum tissue pathology because I disagreed with the two readings done by IDEXX, which indicated hemangiosarcoma. While I was waiting for this renowned vet pathologist's report, an internal medicine vet started Cooper on trilostane. He did a follow up ACTH stim test which came back as 6.2 for the first cortisol sample and 9.1 for the second cortisol sample.

While Cooper was on the trilostane we went to a veterinary cancer group, which is where he collapsed and the critical care unit next door said his glucose was over 750 and his heart rate was 40. They also found that he had pancreatitis and a UTI. I believe that the trilostane caused these issues as his pancreas was normal when he had surgery and before the trilostane. At this point, they treated the diabetes, pancreatitis, and the UTI. They were never able to get his glucose under control, but I thought it was because he should have been on a different insulin besides humulin n. They wanted to start mitotane because they said it would control the diabetes. I disagreed and that is when I went to Dr. Bruyette seeking surgical removal of the pituitary macroadenoma.

When I finally received the third pathology report Cooper was diagnosed as having had a splenic mass that was a low grade leiomyosarcoma.

Dr. Bruyette says that he has spoken with his oncologist and that the prognosis for the splenic leiomyosarcoma is estimated 25% one year survival with no treatment and estimated survival of 50% at one year with treatment. I have found other numbers, so I also disagree with this. But, according to Dr. Bruyette, since the macroadenoma is not resulting in clinical signs and what he has been told is the prognosis of the splenic mass that he would not consider radiation or surgery at this time. He recommends a chemotherapy protocol containing temozolamide because he says that it has shown efficacy against pituitary tumors and can be used in conjunction with doxorubicin for the leiomysarcoma.

So that is where I am at. Still very frustrated because trilostane has done some pretty damaging things to Cooper and his diabetes is still not controlled. I am actually meeting with Dr. Bruyette tomorrow so we'll see what happens.

Do you know anything about the chemotherapy protocol that he recommends for pituitary tumors?

Thanks again for taking the time to help. I really appreciate it!

[labblab]

Thank you so much for all this additional information. Wow, talk about a complicated situation! :o

First off, no, I am not familiar with the chemotherapy protocol that is being suggested. So I will actually be very interested to learn more about it, too. I lost my own Cushpup to what we assume were the effects of an expanding macrotumor, so I am always particularly interested to read about advances int related treatment. At the time my dog died, nearly ten years ago, conventional radiation was really the only common treatment here in the U.S. And even now with the more cutting-edge laser therapies, dogs most often still require cortisol-lowering medication even though tumor reduction can result in a decrease in neurological symptoms.

As for the trilostane...I know you believe that the trilostane was the causative agent for the pancreatitis, UTI, and muscle wasting. However, I am going to throw out an alternative explanation for your consideration. Since Cooper's glucose level was known to have spiked at the time of the collapse and emergency hospitalization, it seems possible to me that the pancreatitis and UTI were associated with the uncontrolled diabetes along with an elevated cortisol level that was still not under optimal control at that time. Medications can certainly carry a host of side effects, but it seems more likely to me that disease processes were the culprits here and not the trilostane. In our experience here even with nondiabetic Cushpups, when cortisol is lowered effectively by trilostane, there is a decrease in the incidence of pancreatitis and UTIs, and also most certainly a decrease in muscle wasting/weakness.

I do realize that due to the synchronicity of the ER crash and the initiation of the trilostane, you are highly suspicious of the drug. But I am thinking that the highly elevated glucose level was also present at the same time and cannot be separated out of the causative mix. I have seen at least one study linking Type 2 diabetes with an increased risk for pancreatitis, and would have to think the same could be true for Type 1 patients. Since we know that Cooper has a diagnosed macroadenoma, I'm fearful that you really will have great difficulty with diabetic management unless the cortisol can somehow be controlled, as well. But therein lies a double-edged sword, because we have been told that Cushing's medication can sometimes paradoxically hasten pituitary tumor growth due to disruption of the ACTH feedback loop.

So I return to "Square One" by repeating that Cooper is indeed a very, very complicated little boy! I will be very curious to know what Dr. Bruyette recommends tomorrow.

Marianne

[molly muffin]

Hello and welcome to the forum.

One of our members dogs went to University of Davis in California and had radiation treatment for a macro. This consisted of only 3 actual radiation treatments as opposed to the older versions that needed more. Her tumor decreased in size and Buttercup is doing fine.

I don't know if that would be an option but you could certainly inquire about it.

This is over all a very difficult case as there are so many things going on. I remember that when Buddy was sick, that Dr. Bruyette was involved in a study on another protocol or medicine for macrotumors. I wonder if this is it.

Sharlene and molly muffin

[charley]

Dr. Bruyette recommended chemotherapy regimen of doxurubin and temozolomide to address the pituitary tumor since I'm not willing to use trilostane. He did not recommend mitotane. In fact, he even said that the use of trilostane and mitotane can cause an increase in the size of the pituitary tumor.

Of course the doxurubin is for the cancer.

Have you heard of any other treatment for the cushings? Dr. B also said that radiation has poor hormonal control of Cushings and that surgery is not possible.

Does anyone know of any other new treatments out there?

[charley]

Molly Muffin:

How is your dog doing after the radiation treatments of the pituitary? Has that helped the Cushings?

[molly muffin]

Hi, my dog wasn't treated with radiation, it was Buttercup another dog on the forum who was and she is doing well as far as I know. Macro decreased in size, skin clearing up.

Her thread is here: http://www.k9cushings.com/forum/showthread.php?t=5850&highlight=buttercup

Buddy is Kathy's furbaby and they didn't enter the study as you had to be in the LA area and they are further south. He unfortunately passed a year ago after a gallant fight.

Sharlene and molly muffin

[labblab]

Hi Charley

It is not Sharlene's dog Molly that had the radiation treatment at Davis, but instead another member's dog, Buttercup. Here's a link to her thread:

http://www.k9cushings.com/forum/showthread.php?t=5850

As you will see, Buttercup was exhibiting neurological symptoms (e.g., one-sided blindness from pressure on the optic nerve) and the aggressive radiation successfully significantly reduced the tumor size. She is still in need of trilostane to control the cortisol level, however, but they have reduced the dose and hope that she may be able to stop the trilo entirely at some point in the future, which would be great.

Dr. Bruyette is correct, though, that the majority of dogs who undergo radiation to reduce the size of pituitary tumors still require cortisol-lowering medication afterwards. The goal of the treatment is to eliminate or control the neurological problems caused by an expanding tumor; it is a lucky fringe benefit if cortisol can be controlled without medication afterwards.

If you don't treat with either trilostane or mitotane, does Dr. Bruyette think you will be able to gain control of Cooper's diabetes? It seems as though those highly elevated glucose levels are probably the top priority right at the moment.

Marianne

[molly muffin]

Hi Carley and Cooper,

Checking in to see if you got any further information from anyone on your next step forward.

Hoping to hear that things are going well for you and Cooper.

Sharlene and molly muffin