Cushing's, Diabetes + Trilostane

[Icaru]

Hello, my name is Gigi, I'm a spayed Maltese nearly 11 years old. I am hoping someone out there might have a similar experience to mine and can give my Mom some suggestions.

In February, 2010 I was diagnosed with diabetes and CHF. At the onset of the diabetes I lost huge masses of my long hair so my doc did some tests for Cushing's. My base cortisol level, cortisol:creatinone ratio and LDDS tests were done. All values were at upper limits of normal range, suspect but not definitive for Cushing's. My Mom contacted Dr Oliver in Kentucky and he suggested I take some melatonin and lignans but no trilostane. I took them for 1 year but they didn't seem to have any effect.

Once the diabetes came under control the massive shedding stopped but my hair kept coming out too much and too easily. My Mom measures my blood fairly regularly with a glucometer and my diabetes has been fairly well controlled over the past two years with 5 IU Humulin N twice daily. No PU or PD. I also take Fortekor and Furosemide for my heart condition (CHF). But in these two years the Cushing's symptoms continued and increased, especially my hair loss and pot belly.

My hair is now very thin, it has shed bilaterally over my flanks and sides (skin now very visible); my skin is darkly pigmented and scaly, my hind legs are weak and sometimes I don't walk straight. I have a slight pot belly, and I am sometimes unresponsive or confused when my Mom calls me. She says that I often just stare off into space. In these two years since I was diagnosed I also had 3 episodes of calcinosis cutis.

ACTH stimulation test was repeated in 12/2011 and again results were borderline but not definitive for Cushing's.

We decided to try Trilostane 30mg/day (she stopped giving me melatonin and lignans before starting Trilostane). We started on Dec 24, 2011 with 30mg once day. First ACTH test at 2 weeks showed some but inadequate suppression of cortisol. Second ACTH test at 4 weeks on Trilostane showed an increase in cortisol! Around day 50 of treatment, I began to lose weight, demand more food, need more insulin, urinate more frequently -- all signs of cortisol increase.

Although my pot belly has disappeared, my diabetes and BG levels are now not nearly as well controlled as before starting Trilostane. I pant more often, I am very lethargic. It seems that I am experiencing an increase in cortisol instead of a decrease. IOW, we are getting the opposite result of what is expected ! My vet wants to increase Trilostane, my Mom is thinking of stopping it altogether.

Does anyone else have a similar experience with a diabetic dog on Trilostane?

[mytil]

Hi and welcome to our site. I am sorry you are having these troubles.

Firstly, here is a great site on canine diabetes - http://www.k9diabetes.com/forum/.

I would like for you to post the actual results of the tests performed for Cushing's. You mentioned the results were borderline when you started Trilostane. I do not have direct experience with both Cushing's and Diabetes, but I do know both make it more difficult to regulate both.

Keep us posted
Terry

[Squirt's Mom]

Hi and welcome,

Please do visit our sister site asap - k9diabetes.com

I agree - stop the Trilo now. In a recent post here to another member, Natalie from k9diabetes, said that she has seen diabetic pups that just do not do well on the Trilo and it sounds as if Gigi may be one of these pups.

Has her thyroid been checked recently? Is she taking any meds/supplements/herbs other than her insulin, Fortekor and Furosemide?

Some of what you are seeing could be due to the meds, in particular the Furosemide -

http://www.1800petmeds.com/Furosemide-prod10083.html


What are the possible side effects of furosemide: If any of the following serious side effects occur, stop giving furosemide and seek emergency veterinary medical attention; an allergic reaction (hives, difficulty breathing, swelling of the face, lips, tongue, or throat). Stop giving furosemide and call your veterinarian at once if any of these serious side effects occur; dry mouth, thirst, nausea, and vomiting; weakness, drowsiness, restlessness; irregular heartbeat; muscle pain or weakness; urinating less than usual or not at all; bleeding, unusual weakness; hair loss; "bulls-eye" lesions; vesicles around mouth, ears, and groin; hearing loss; nausea, stomach pain; fever; loss of appetite; dark urine; jaundice. Continue giving furosemide and talk with your veterinarian if any of these less serious side effects should occur; diarrhea, constipation, or stomach pain; headache; dizziness, or blurred vision. Side effects other than those listed in this guide may also occur. Talk to your veterinarian about any side effect that seems unusual or especially bothersome to your pet.

Has your vet discussed other options with you?

If Gigi has not had an abdominal ultrasound, I strongly recommend she does.

Looking forward to seeing test results and learning more about Gigi. Now, go see k9diabetes right now and tell her story there as well - they are the canine diabetes experts! :)

Hang in there!
Hugs,
Leslie and the gang

[Icaru]

Regarding the Cushing's tests that were done, the 1st tests were done at the same time she was diagnosed with diabetes. Here are some of the results (1 missing, have to ask vet - PS. We live in Spain so all these values might be slightly different from US labs, not sure):

Feb 10, 2010 - Cortisol:creatinine ratio - NORMAL
Gigi: 35,93 x 10E-6 normal range: 0-60 x 10E-6

Feb 18, 2010 - Cortisol Snap test, Gigi: 4.7 - NORMAL

March 2011 - LDDS test - normal

December 14, 2011 - 1st ACTH Stimulation Test - be4 Trilostane
Basal Cortisol: 2.31 ug / dL
Post ACTH: 20.20 ug/dL - borderline, suspect Cushing's but not definitive

January 4, 2012 - 11 days after starting Trilostane
Gigi: Basal cortisol: 2.12 ug/dL
Post ACTH stimulation: 2.82 ug/dL

January 18, 2012 - 25 days after beginning Trilostane
Gigi: CORTISOL BASAL 5.83 μg/dL ( 1 - 8 normal range )
CORTISOL POST-ACTH 7.64 μg/dL

3rd ACTH stimulation test will be done on March 13 (day 82 of Trilostane treatment)

I posted extensively in the k9diabetes forum in early 2010 when Gigi was first diagnosed and I received many good suggestions. I will post there again but the problem now is not so much the diabetes as much as the Cushing's - typical or atypical as I have suspected for these intervening 2 years.

Her diabetes and the use of Furosemide has never been much of a problem since we got the insulin regulated in May of 2010. A diuretic like Furosemide is extremely important to drain off excess liquid that causes pressure on an enlarged heart due to CHF.

The insulin 'deregulation' problem has started recently about 7 weeks after we began the Cushing's treatment, i.e., Trilostane (and stopped the melatonin + lignans), but I cannot be sure that the BG increase and increased appetite is directly related to the Trilostane. It could be coincidental.

[Icaru]

Since Feb 2010 our Maltese has suffered from congenital heart failure, hyperestrinism and diabetes. For 2.5 years I treated her with Vetoryl but quit that about 6 months ago. Since then she has been following the suggestion of the late Dr Oliver: melatonin and HMR lignans.

She has not suffered any visible deterioration but I would like to hear from other owners who have treated their dogs with this combination, and with what results.

Many thanks from Gigi.

[Squirt's Mom]

Hi and welcome! :)

My Squirt started out on melatonin and lignans because she was diagnosed with Atypical Cushing's, meaning her cortisol was normal but intermediate hormones were elevated. This is the only form of Cushing's that can be treated with the melatonin and lignans. If the corisol is elevated, the pup needs either Vetoryl or Lysodren - lignans and melatonin will have no effect on cortisol and it will continue to do damage if left unchecked. IF the intermediates are elevated along with cortisol, Lysodren is the preferred treatment by UTK.

Squirt was on the lignans and melatonin for a few years and they worked to lower her intermediates as proven via the specialized ACTH performed at UTK (the only place we know of that does this sort of testing. ;)) Then her cortisol started to rise and she was put on a maintenance dose of Lysodren along with the melatonin and lignans. She took the Lyso 3-4 times a week, the supplements daily.

Can you tell us more about your baby? What tests were done to diagnose the Cushing's and what form she has - Atypical or conventional (meaning the cortisol is elevated)? Would you mind getting copies of all the testing done for this diagnosis and sharing the actual results here? That will help us a great deal in helping her. The more you can tell us about your sweet baby girl, the better. We LOVE details so don't worry about writing a book! :D We want to know all about her health history in particular along with all those test results. We also need to know her age and weight, all meds she is taking as well as any herbs or additional supplements she is on.

I'm glad you found us and look forward to seeing more info about her very soon.
Hugs,
Leslie and the gang

[lulusmom]

Hi and welcome back.

It's been a long time and apparently a lot has happened. I have merged your two threads so that we have all of Gigi's history in one place.

Is Gigi still on insulin? Why did you discontinue Vetoryl? Did you see a spike in blood sugar when you discontinued. When was the last acth stimulation test and can you please post the results for us?

Glynda

[Icaru]

Thank you for your interest and sorry for the late reply. To summarize earlier info, our Maltese, Gigi, is 13.5 years old, has diabetes, congestive heart failure (CHF) and hyperestrinism, aka atypical Cushing's. She takes Fortekor, Lasix, insulin, melatonin, lignans and milk thistle for fatty liver. (Much of this is inherited and is a result of backyard inbreeding, buyer beware.)

Gigi's test results: We live between Spain and Turkey. Her tests were all done here in Spain, both urine/cortisol ratio, ACTH and LDDS. The results were inconclusive, cortisol remained borderline, never elevated but the clinical signs were (and still are) present and increasing. Here in southern Spain, most vets do not know about / believe in "atypical Cushing's". Several told me that if the ACTH and LDDS tests were borderline, i.e., high normal, there was no Cushing's.

However, seeing the progression of all the clinical signs, I took it upon myself to give Gigi Vetoryl for 2.5 years at which point I found a specialist and he did an ultrasound and an adrenal panel. That showed an enlarged gland and super high estrogen levels (partly explained by Vetoryl which tends to raise estrogen levels). As melatonin is in the cortisol pathway, it should have the effect of lowering cortisol as well as other intermediary hormones. I decided to stop the Vetoryl and try the standard melatonin/lignan treatment which she is still on.

Anyone who has ever done any kind of hormonal testing knows how the results can vary wildly according to the test protocol, the lab, the physical state of the person/animal ... so my treatment protocol has been the old method of trial and error. See what works. I cannot say with any confidence that either the Vetoryl or the melatonin/lignans have had any sure effect but I decided to opt for the lesser evil. Lignans in any case are merely antioxidants, they won't harm her. Melatonin ... well, at 13.5 she sleeps a lot anyway and it will bring down the high estrogen level. In fact, her vulva was quite enlarged and has now returned to normal so this physical change is certainly due to a decrease in sex hormone levels.

In both treatments I saw no difference in her other physical symptoms (primarily hair loss) or as regards her diabetes. If anything, there might be a positive effect on the diabetes from the melatonin/lignan treatment as her insulin need has decreased since I stopped the Vetoryl but she was also put on a diet at about the same time. She lost about 15% of her weight over a period of months (for the good of her heart), so the lower insulin need may only be related to her weight loss.

Her hair has now fallen out almost completely from her sides and flanks, she is beginning to have the small skin cysts that some dogs get with Cushing's. Her back legs are weak but she is still lively and bouncy at 13.5 years old. She still gets insulin injections 2x daily to control her diabetes and her heart is now so big that it occupies the entire chest cavity, but she doesn't cough and can still breath with only a slight, mostly unnoticeable wheeze.

All of the 5 vets that have examined Gigi since February, 2010 have said that she would not live much longer. Gigi fortunately did not listen and has no idea anything is wrong with her. She loves life, is alert and interested in everything around her, trots around, eats well, doesn't run into furniture even though she is 90% blind. Still the imp she ever was!

ACTH results: after 2011 I did not do them again as I discovered that the serum sample was not being adequately preserved. The samples have to be sent to Barcelona or Madrid and should be sent in special dry ice containers. These are not available here except to hospitals in bulk but you cannot buy them as an individual. So the vets were sending the serum samples by mail with picnic ice packs like pharmacies use. This may have invalidated the test results (even though they were consistent). So I decided it wasn't worth doing them again.

[labblab]

Thank you so much for returning and giving us this update on little Gigi! You have obviously taken great care to arm yourself with as much information as you can possibly gather on her behalf, and Gigi's story is a very interesting case study to be archived here on the forum. What a little sweetheart and what a survivor!!

You have really covered all the bases in terms of your treatment decisions. There is only one "wild card" question that occurs to me in the face of the hyperestrinism. By any chance, does any human with whom Gigi comes into contact use any type of topical hormone supplementation? The swollen vulva caught my eye because per this article, that is a symptom commonly displayed by dogs who have unwittingly received hormone supplementation secondary to exposure to lotions/sprays/patchs used by their owners. As I say, just a crazy possibility to throw out there.

http://www.k9cushings.com/forum/showthread.php?p=36843#post36843

Thanks again, so much, for updating us. And we will be hoping for additional updates to come!

Marianne

[Silliam]

Glad to hear the estrogen is reducing some what. I know hormones can also play havoc with hair and skin issues. Will be reading along as my dog is cushings diabetes and now cardio too.

[Icaru]

Good question but no hormones of any kind used in this house since was before Gigi was born ! So no, she has never been exposed to any kind of estrogens or progesterones.