OT...results of pilot study on use of Cabergoline in Acromegaly

Neither is 90 days long enough to study the effects of the drug. We've had more than 9 cats on cabergoline, over half with reduced doses as a result, 3 going OTJ. Most report improvement in symptoms, such as stridor. Likely as a result of growth hormone output reduction - which this study did not measure. IGF-1 also isn't necessarily improved in cats undergoing SRT (like Neko had), but her dose went down, acro symptoms were reduced and her QOL was greatly improved. Of course, my observations were over longer than 90 days too.
 
:)Hi

@Chris & China (GA) @Wendy&Neko

I was able find a copy of the full study online. The Formatting is a little off but it’s not an issue :).
https://researchonline.rvc.ac.uk/id/eprint/12988/1/12988_Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus_GREEN AAM.pdf

First, I am sure you know that every study issues a final statement pertaining to the results of their specific study which is based on their hypothesis or what they are studying, so by no means were the authors issuing a “blanket” statement that it was not effective. Unfortunately, the abstract available for this particular study was very short. Once you get into the full study, and specifically, the “Discussion” part of a/the study, they discuss the limitations of the study as well as some thoughts about what may or may not have effected the results and ideas of where they (or someone else) needs to go moving forward with the Re arch. That’s good research—generate some more questions or direction to go with future research. Move the ball forward.

What is consistent now across this particular study, the prior study using 3 cats that influenced this study (http://www.scielo.org.co/scielo.php?script=sci_abstract&pid=S0120-06902017000400316) and what they are finding within research with humans is that there seems to be some cats who will experience better or more robust results (as maybe you have seen in your experiences) & they are trying to determine which cats those would be and more important, why, so they know what specific cats they should even try this medication with.

Based on what is known or so far, and they are still trying to figure it out, but for those cats who do respond:

1) May have less severe HST

The 3 cats in the prior study in which there was a response did not have the severity of HST like the cats in this latest study.

2) Pituitary Size is smaller

There has been some evidence that there may be a negative correlation between DRD2 protein expression and pituitary size. The thinking is that there is a loss of DRD2 expression in larger tumors-and therefore, a dopamine agonist such as Cabergoline will not work well or at all with those cases. This is also noted in the latest Feline Endo textbook.

* They did not find this correlation in this paper but acknowledged it still may be an issue based on other studies, understanding of the tumors

3) Dosing may be higher

They recognize, that in this study, they started at a lower dose 5ug/kg q24. They based their initial dose on 1) licensed dose for the use of the drug for inappropriate lactation in cats 2) dose was effective for terminating pregnancy in cats which show effective suppression of prolactin secretion and 3) dose is equivalent to what has been successfully used for GH suppression in humans with acromegaly.

They did increase the dose to 10ug/kg q24 with some cats and noted that there is some indication of a need of a higher dose in cats. Pharmacokinetics are unknown for cats but in a study that used this particular drug in cats to induce abortion, higher doses were utilized. Also, higher doses are often needed in human cases to get a response.

4) SUBTYPE of Pituitary Adenoma

Different subtype will respond or not respond to specific therapies, medication management

5) Functional or more robust DRD2 Signaling Pathways, Expression vs non responders

I am going to link one additional study that you may already have:

“Pituitary Pathology and Gene Expression in Acromegalic Cats” published 10/2018.

I think it really does a nice job describing receptor expressions in these cats and how it effects treatment effectiveness. The thought that the DRD2 expression becomes limited or eliminated is important. If/when that occurs, not only is there little hope of Cabergoline working but it also is likely to result in larger pituitary tumors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316999/pdf/js.2018-00226.pdf

It would be interesting to go back to the cats who have had success on this forum and find out about dosing as well as other variables that may explain their success:). Were there some who didn’t respond and how were they different?

Amy



 
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You are welcome! It does have some good info, especially with respect to giving themselves and others some additional ideas of where to go from here.

The Pituitary Pathology and Gene Expression study is awesome. They’ve done a deep dive in that one and it makes sense why the more expensive medication does such a better job with HST once it has progressed.

I think the take away for me is there is a need to jump on diagnosis early vs once this has progressed. There is recommendation out of the UK to check every cat when diagnosed with DM vs waiting for uncontrolled DM to present. It makes a lot of sense but it will be interesting to hear what other IMs think. I see more benefit vs risk so why not?
 
I didn't notice that you posted this! I actually just created a post tonight in the acro group with some questions. Some good information here! Thank you!
 

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Tomlin said:
there is a need to jump on diagnosis early vs once this has progressed
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Bingo! That's been our experience here. The sooner you can get started after a diagnosis, the better the results.

I'm reaching back into the memory vault, but I think every acro cat that has tried this so far, except one, was on less than 20 units of insulin when they started cabergoline. Of the three that went into remission, one was six months after the diabetes diagnosis, but the other two were over a year after. None of the FDMB cats on cabergoline have had imaging done, so we don't know the size of the tumours. Well, except for Bronx, who was close to 30 units when Paul did a very short trial, before deciding to do SRT instead.

Thanks for the paper link Amy. And thanks Kel for the readable one! When I discussed this with Chris Scudder when he put the call out for acros for the study, his main objective was to find a treatment that reduced IGF-1. Cabergoline didn't seem to do that, in his study. His was the second study of cabergoline. An early, smaller one in South America had better results as this paper recognized. And as I mentioned above, even if you don't tackle the IGF-1 problem, cabergoline can still improve QOL, unlike the conclusion in this paper.

Most of the cats here have used the higher dosing.

I wonder how they measure "severity of HST"? It's doable, but not on my high priority list to compare IGF-1 dx numbers on kitties here and how they did on cabergoline. However, I did take the time to check the three cats that went OTJ, and their IGF-1 was all in the 300's. Odd? That translates to over 2300 ng/ml. And contradicts the statement in the paper that cats with IGF-1 over 2000 ng/ml were unsuitable for cabergoline therapy. Before Chris Scudder published the results, he was made aware of Marvin (first cabergoline kitty to go OTJ here).

One day, it'd be nice if someone took the time to extend this pilot study. I did hear that Chris had commented that they found combination treatment with octreotide improved results. Without cabergoline, the only other treatments available cost at least $10,000 and require travel to the few places that do it. Out of reach of many acrocat parents. Cabergoline may not be perfect, but it's better than no treatment and a lot cheaper than surgery or radiation therapy.
 
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