Maisie - Can Trilostane cause tumors to grow?

Hello,

My Maisie was diagnosed with Cushing's disease in the fall of 2009 following a tooth being pulled.....surgery. The diagnosis was directly after the surgery and we always felt it was somehow linked. My baby passed away 3 weeks ago. I am so devastated. Words cannot describe the loss and my sadness.
I read that your dog Alivia was diagnosed after two teeth being pulled. I wonder if the stress of the surgery brought on the Cushing's. Maisie was on Trilostane. Whether the tumor grew on her pituitary from a micro adenoma to a macro adenoma or else a new brain tumor grew they could not tell me. She was so weak from the disease from having it almost 2 years I opted out of an MRI. The doctors said it would have told them what they already knew anyway.
Where did you hear that Trilostane can make tumors grow faster? Could you please let me know your resource for that information?

I am so sorry for your Avilia.

take care,
jani

PS. Jani, I copied your post from Alivia's thread so that you can receive more response to your questions from our members. Your original post is still in her thread, too.

Jani, I am so sorry to hear about your Maisie. The pain can be so hard to stand especially after caring for her and trying so hard.

I am hoping others will be along soon to voice an opinion on your question.

In the mean time, please know we are here for you.

Hugs,
Addy

Jani, I am so sorry for the loss of your Maisie. My thoughts and prayers are with you.


xoxo,
Cindy, Alex and Bear

Thank you Addy and Cindy. I tried my best to make her comfortable.
I cooked all of her meals. I read somewhere to get her off of commercial dog food asap. There are no regulations on pet food. Or minimal anyway. All her meat came from Whole Foods....I wouldn't even trust Safeway for her meat. Mixed with fresh organic veggies and brown rice, along with vitamins. The pain is enormous. I know that she was ill and this disease was going to shorten her life, but the brain tumor just happened so fast. It was so painful.
Somehow, her tumor grew. I wonder if the Trilostane had something to do with it? She weighed 24 lbs and the vet had her up to 170mg a day. 100mg in the morning and 70mg at night. They are vet specialists in SF. How much Trilostane are other dogs taking?

thanks,
jani

Dear Jani,

I am so sorry for the loss of your Maisie. But I am really glad that you have found us, because we will be here to support you in your sorrow. And I surely do understand that talking over some of your questions may feel very important to you right now. At least, that's the way it felt to me back when I lost my Cushdog to what we assume was a rapidly enlarging pituitiary tumor (although we did not opt for an MRI, either).

I am not a vet, so everything that I write here is based only my own reading and my own experiences as a member of this forum. But I do not believe that the tooth extractions would have played any role in the development of the pituitary (or adrenal) tumors that cause Cushing's. It is often the case that Cushing's ends up being diagnosed at the time of a surgical procedure, because routine blood panels performed in conjunction with surgery may reveal specific lab elevations that are associated with Cushing's. But the tumors that cause the Cushing's have been developing for a period of time prior to the surgery -- the "big picture" just had not yet been recognized or diagnosed.

Secondly, though, we did learn through our experience with our Cushpup that researchers suspect that in some cases, treatment for Cushing's may end up hastening the growth of an associated pituitary tumor. This is because of disruption to the normal feedback loop that controls production of ACTH. Here's an explanation from an article in our Resources section:

Quote:

---

Because most chemotherapeutic agents have no effect
on the pituitary itself, they do not inhibit ACTH secretion,
which may actually increase with therapy.This phenomenon,
known as Nelson’s syndrome, has been well
documented in humans with pituitary tumors treated
with bilateral adrenalectomy. Nelson’s syndrome refers
to rapid enlargement of a pituitary mass that occurs after
loss of negative feedback from adrenal cortisol production,
which has an inhibitory effect on ACTH release.
While this phenomenon has been suggested to occur in
dogs, studies have shown no correlation between
treatment with mitotane and pituitary size or rate of
pituitary tumor growth. However, because the exact
mechanism behind the development of Nelson’s syndrome
is not completely understood, the potential for tumor expansion
as a result of adrenal corticolysis or decreased cortisol production seems plausible.

---

http://www.k9cushings.com/forum/showthread.php?t=229

The above 2008 article says that no correlation had yet been established at that time with treatment by mitotane (Lysodren), even though it seems reasonable that the potential for that treatment effect does exist. When my specialist told us about this possible effect back in 2004, trilostane really wasn't being used widely in the U.S., even though that is what we were using to treat our dog. So based on my specialist's comments, I assume that it was mitotane that had already been theoretically linked to this effect.

However, here's a 2009 article that also makes a possible linkage between trilostane and this effect:

http://www.ncbi.nlm.nih.gov/pubmed/19041802

Quote:

---

Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis
Domest Anim Endocrinol. 2009 Jan;36(1):32-44. Epub 2008 Nov 11.
Teshima T, Hara Y, Takekoshi S, Nezu Y, Harada Y, Yogo T, Teramoto A, Osamura RY, Tagawa M.
Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan

Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported. However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect.

The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary-adrenal axis in clinically normal dogs.

Dogs were administered 5mg/kg trilostane twice a day every day for 8 weeks (n=8) or 16 weeks (n=3). After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably.

As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged. After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals.

In addition, histological examinations revealed bilateral adrenal cortical hyperplasia. Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs.

These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs. These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease.

---

I want to stress that this possible effect probably should not be a reason for owners to opt out of Cushing's treatment. Regardless of the cause, it is not common for canine pituitary tumors to enlarge to a size sufficient to cause major neurological problems. And so when weighing quality of life issues, it is important to consider the damage/discomfort that is known to be associated with untreated Cushing's in symptomatic dogs. My own dog was miserable prior to starting trilostane treatment. He then had several months in which he rebounded prior to exhibiting serious neurological abnormalities. So even had I known that the trilostane might hasten the growth of his enlarging tumor, I still would have chosen to treat for those months in order to relieve him of his awful Cushing's symptoms. I don't know if this is the type of information you were hoping to find, but I hope it will help.

And just as a P.S., my boy also required a very large dose of trilostane in order to keep his cortisol under control. I don't know whether or not that was related to the fact that he probably already had a large pituitary tumor, even at the time that treatment was begun. But he was on a very large dose in relation to current recommended dosing protocols.

Marianne

Hi Jani and welcome.

Thank you for your concern for Alivia when you are going through such pain yourself. I am so very sorry for the loss of your sweet Maise. I can only imagine how devestating that must be. It sounds like you did everything possible for her. You went above and beyond to care for her and she was very lucky to have someone who loved her as much as you did. You deserve to take some comfort in knowing you did everything possible for her.

In hindsight, I think my Alivia has had mild symptoms of Cushing's for some time. I don't think the dental surgery caused her Cushing's but I do think (however, this is only my lay opinion) the anesthesia from the dental surgery and/or the stress of it all may have exacerbated her symptoms. But, getting treatment for her 2 absessed teeth was not optional. I'm guessing Maise's dental procedure was just as needed. Alivia has an adrenal tumor and offhand I can't recall where I read about the possibility of Trilostane causing those to grow faster but, I will look through my research and get back to you on that. Please, please don't second guess yourself on your decision to treat Maise with Trilostane. There is so much contraversy on which medication is best and under what circumstances even among the top experts. Lysodren also has potentially serious risks (some even scarier than Trilostane), and there are also serious risks with not treating at all. Sometimes tumors are just fast growing and nothing you could have done or not done would change that. It is clear that you did the best you could for her with what science is currently available.

Please post some pictures of Maise and tell us more about her. What breed was she? You will be in my thoughts.

I'm so sorry for your loss, Jani. My thoughts and prayers are with you.

Terri

Maisie was a wired haired Jack Russell terrier. I love her beyond words. I always will. I cry every day because of missing her so very much. I can't believe she's gone. She was only 11.5. She was extremely smart, sweet, flawlessly beautiful and well behaved. We were very connected. I would love to post some photos of her, but I'm not sure how to do it. Is it easy?

About her tooth surgery suspicions. She had a full blood panel prior to her surgery and everything came out perfect. Which is what they do before to make sure the dog can handle the anesthesia. She never had any symptoms of Cushing's prior to this surgery. But afterwards, both my boyfriend and myself noticed changes in her. It was right on the heels of the surgery. The stress of it might of pushed her over...just not sure. She was only 9.

Thank you Marianne for all of your information. In the end it was pretty brutal for her. The tumor had grown or another tumor had grown, the vet did not know if it was a macro adenoma or another tumor. I think I would have opted out of Trilostane if I knew this is how it would have ended thats all. I never would have used Lysodren.
The idea of destroying the adrenals sounds crazy to me. There just are not many options I guess. I am finding everything I can about Trilostane...for what reason, I'm not sure. I think it helps me for some reason. Just having more information. This is a serious disease. When humans have it, they have surgery. That's their only option.

thank you all for your kind words!

jani

Jani, it will be wonderful for us if you are able to upload some pictures of Maisie. If you have digital photographs stored on your computer, the process is really very easy. Here's a link to the portion of our "Frequently Asked Questions (FAQ)" menu that includes the creation of photo albums and also how to add an "Avatar" (or little photo) of Maisie that will always appear alongside your name when you post replies.

http://www.k9cushings.com/forum/faq....3_user_profile

Also, I can indeed relate to your desire to try to figure out what happened to Maisie. I spent a lot of time reading and researching after I lost my Cushpup. There were both good and bad aspects to it for me. The good part was that it helped bring some closure to what had happened, since we were left with some important unanswered questions. And the best part is that I learned a lot in the process, and I have since been able to share that info with other folks who come here. That has felt like a special way in which I have been able to continue to honor the memory of my boy.

The not-so-good part was that I spent quite a long time second-guessing the decisions that we made. And that made the pain of missing him even worse. I hope you'll be able to spare yourself that part of things. I finally found peace in accepting that even if we did make mistakes, we made the decisions that we thought were the very best for him given what we knew at the time. And he always knew how much we loved him. Always. It took a long time to arrive at that place, but now my memories are primarily of all the good times. And that is a blessing.

Jani, if you should ever wish to start a thread in Maisie's honor on our special "In Loving Memory" forum, it will be our privilege to share in your memories of your precious girl. You can write whatever you want there, and we will remain with you every step of the way.

Sending many hugs,
Marianne

Jani -

Now I know what drew you to my string! We are both JRT lovers!! They can be so sensitive and intuitive and somehow they manage to own your heart.

I have two, rough coated Jacks. Alivia (13 years old), who of course is the reason why I am here and Maxwell, who will be 11 in August (and fortuantely has always had perfect health!). Your Maise sounds just like my Alivia, so I can truly understand your connection to her and the pain you are feeling. I have never experienced a loss like yours, but I know when it happens, I will not handle it well.

I'm glad you found this place because the people here truly get that your dog was a family member and not a possession that can be replaced. You took awesome care of Maise, so as Marianne said, please don't regret your decisions. The experts do not agree on the best treatment, so all you could have done was to try your best for her. And, that you did!! I am sure she knew she was loved.

Posting photographs is super easy if you have any digital ones on your computer! Marianne directed you to the instructions. I am anxious to see pictures and when you feel up to it, it would be nice to have a memorial here for Maise, as well. I am so terribly sorry for your loss. I wish there was something I could do to ease your pain. You mentioned how brutal it was for Maise in the end. I am so sorry you both had to go through that. I hope those awful memories fade in time and you remember your beautiful, sweet Maise and all of the good times you spent with her.