Potential cutaneous hypersensitivity reaction to an inactive ingredient of thyroid hormone supplements in a dog

[helvella]

For a change, it looks as if some vets should be looking at humans! At least, some of the humans who inhabit this forum.

This rather surprising story identifies a possible reaction to excipients used in some levothyroxine products. Unlike many human patients, this canine was not told it was all in their head.

Vet Dermatol. 2016 Feb;27(1):53-e16. doi: 10.1111/vde.12281. Epub 2015 Dec 21.

Potential cutaneous hypersensitivity reaction to an inactive ingredient of thyroid hormone supplements in a dog.

Lavergne SN1, Fosset FT1, Kennedy P2, Refsal KR3.

Author information

1 Department of Comparative Biosciences, University of Illinois-Urbana-Champaign, College of Veterinary Medicine, 2001 S Lincoln Ave, Urbana, IL, 61802, USA.

2 Northern Illinois Animal and Bird Hospital, 3202 Northwest Hwy, Cary, IL, 60013, USA.

3 Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, 4125 Beaumont Road, Lansing, MI, 48910-8104, USA.

Abstract

BACKGROUND:

Although discussions about allergic reactions to thyroid supplements abound on professional forums, there is almost no information in the literature on these specific idiosyncratic drug reactions.

ANIMAL:

A dog with a history of hypothyroidism-associated weight gain and mild lethargy was prescribed levothyroxine tablets (0.018 mg/kg twice daily). After 19 days the dog developed a severe skin condition that was responsive to levothyroxine withdrawal, and antibiotic and glucocorticoid therapy. Three weeks later a different levothyroxine tablet was prescribed. Within 48 h the dog developed a more severe cutaneous reaction that resolved with drug discontinuation and appropriate topical care.

OBJECTIVES:

To confirm a possible hypersensitivity reaction and identify its chemical target.

METHODS AND RESULTS:

The two prescribed levothyroxine formulations shared two inactive ingredients: magnesium stearate and polyvinylpyrrolidone. Nine months after discontinuation of thyroid supplement, a formulation without either of these two compounds was used for a second re-challenge. There was no recurrence of the drug reaction and after 1.5 years of treatment the dog remains normal.

CONCLUSIONS AND CLINICAL IMPORTANCE:

These elements strongly suggest that this dog had an idiosyncratic reaction (likely immune-mediated) against one or both inactive ingredients in the first two formulations of levothyroxine. We are not aware of any previous confirmed delayed hypersensitivity to a thyroid supplement in a dog with the likely chemical trigger being an inactive ingredient rather than the therapeutic agent itself. We hope that this case will raise awareness about allergic reactions to thyroid supplements and allergic reactions to inactive formulation components.

© 2015 ESVD and ACVD.

PMID: 26748887 [PubMed - in process]

ncbi.nlm.nih.gov/pubmed/267...

Full article (though not much more than above):

onlinelibrary.wiley.com/doi...

Polyvinylpyrrolidone - also known as povidone:

en.wikipedia.org/wiki/Polyv...

[shaws]

I had to laugh at this excerpt:

This rather surprising story identifies a possible reaction to excipients used in some levothyroxine products. Unlike many human patients, this canine was not told it was all in their head.

I am sure animals are better treated than many humans due to the vet having the sense to take everything into consideration not just the blood test.

[Clutter]

Helvella, I suspect a human patient would have been told "it's not your thyroid" or "Levothyroxine doesn't do that"

I wonder whether it is the Polyvinylpyrrolidone in Tiromel which upsets Tiromel users? Magnesium stearate seems to be an excipient in most tablets.

[helvella in reply to Clutter]

Well, the vet might have said that to the dog. But at least it wouldn't have had any effect on the poor beast.

To me, it seems perfectly within the bounds of possibility that magnesium stearate and/or polyvinylpyrrolidone cause problems only when made into thyroid medicines. Why? No idea. What can be done? Well, look at Tirosint. (Though it is grotesquely over-priced and, in the UK, next to unobtainable.)

[Clutter in reply to helvella]

Helvella, Maybe it's because vets are attuned to non-verbal signs that they don't 'patient' blame.

[TSH110 in reply to helvella]

How about NDT Rob? It works well for dogs but I have not met a vet that knew anything about using it. I think some in the USA do.

[Hidden in reply to Clutter]

I have to admit I was offered this theory with my allergic reaction to thyroxine. This was discussed with an allergy consultant with regard to the excipients. They checked my t3 tablet excipients and t4excipients and they were identical therefore it was the t4. I was told "nobody is allergic to thyroxine ".

I'd been interested to know if anyone else is?

[TSH110 in reply to Hidden]

Mabsie, what on earth do you do if you are allergic to thyroxine? Or is the T3 form ok?

[Hidden in reply to TSH110]

Hi, I manage ok on t3 but the endo. does worry about it. it is much more expensive for the NHS I am told. Thanks for the concern TSH110 x

[TSH110 in reply to Hidden]

Yes as I understand the drug companies kept it generic so there is no price control and they can charge what they like. It is a lot more expensive than in part of Europe, but that is not your fault and if you need it you should get it!

[helvella in reply to TSH110]

Actually, it was more that MercuryPharma changed from being branded to being generic in the case of liothyronine. If it had just been how things happened to be, there would still be anger, annoyance, upset, etc. But the fact that they POSITIVELY brought about this state evokes fury.

[TSH110 in reply to helvella]

Thanks for clarification Rob and rightly so te the indignation it is immoral practice on their part

[helvella in reply to Hidden]

It is entirely possible that each active ingredient and each excipient is, on its own, innocuous. But when they are combined, and they are in the complex biochemical environment of the gut, who knows how they might interact with each other?

Of course, an ingredient by ingredient evaluation is the obvious first step. In some cases that might reveal the culprit. In the case of levothyroxine the strange reports about its unexpected and unexplained effects have been going around for decades.

[Hidden in reply to helvella]

I'm still very ignorant on things I'm afraid. I'm living and learning very slowly. Thank you helvella.

[helvella in reply to Hidden]

Mabsie,

Glad you can join me in the Corner of Ignorance.

The more I find out, the less I know.

[Hidden]

On a light note Helvella you are encouraging my simple sense of humour which surfaces occasionally!!

When watching a recent advert for dog food mentioning hormones ,I said to hubby "perhaps we should try some " !!!!!

[TSH110]

I have had three whippets with hypothyroidism (all closely related and now deceased) one never got diagnosed (the mother) but in retrospect she shared many of the symptoms of it presented by her offspring and with developing it myself, I realise now she had it too. I raised the possibility of it in the daughter with my vet, who (along with several others over the years) did not suggest it as an underlying cause for the endless visits with ear, foot and eye problems plus she was the fattest whippet you ever saw with an insatiable appetite, she had a big bald patch on her tail and phantom pregnancies plus she seemed distant and sad as time went on - all highly diagnostic. The son developed it too but I was on the case by then. They did better on NDT than levothyroxine. All three died prematurely for the breed.

It would seem similar problems exist with diagnosis for human and canine sufferers.

However, once receiving treatment, unlike me, it was never suggested the problem was just in my dogs' head! A full panel test is recommended for sighthounds because of their low body fat and propensity for hypothyroidism so T3 is routinely tested for. NDT totally sorted my "psychosomatic" symptoms where levothyroxine failed...All in my head? What Tommy rot.

Thanks for posting.

We owe a lot to all those poor dogs (many of them were greyhounds) who died in gruesome experiments that helped to elucidate hypothyroidism.

[Hidden in reply to TSH110]

Hmm, I'll tell my sister about this as she has a whippet! Thanks for that TSH110.

[guysgrams in reply to TSH110]

I also have a cocker spaniel that is hypo and had to push to get tests done on her. She was a regular at the Vet from almost the beginning and it took over 6 years to get a diagnosis. She is 12 now and has other issues not sure if some are related or not. Often wonder if she is optimally medicated as we still have issues with the skin and sometimes ears. I keep being told she is 'allergic'

[TSH110 in reply to guysgrams]

Problems with skin and ears are one that ring hypothyroidism alarm bells. Two of mine had ear problems like puffy ear - they went like samosas then eventually shrivelled and all muscular control of the ear is lost so they flop never to prick up like a normal whippet ear ever again. One had it on one ear the other both ears. One also got horrible problems with the skin around her nails and interdigital cysts which are very painful and common in hypothyroid dogs. Eye problems are another onenthey had - the eye became red and inflamed and wept profusely and they were clearly in pain. Treatment consisted of sewing up the eye lids for 3 weeks in the hope the ulcers healed. One of mine suffered a stroke I presume due to the anaesthetic and being undiagnosed hypothyroid and ended up with a wonky face, but thankfully most of the one sided paralysis resolved. After treatment for her thyroid the eye ulcers ceased. Imagine how bad I feel having seen them suffer with these problems and put them through all those horrible procedures when it was so utterly unnecessary and just treating the symptoms and not the cause. If only I had known then what I know now..... I saw at least 5 different vets over many years and not one suggested autoimmune disease as a cause. Oddly, and I remain somewhat sceptical as to its real efficacy, in desperation I tried homeopathic occuloheel drops in the eyes for the ulcers and on both occasions they cleared up. But treating the underlying hypothyroidism was the only thing that put paid to these horrible symptoms for good. another of my whippets is getting those interdigital cysts and is getting rather portly and anxious but no other clear symptoms so he is getting tested I will be really unlucky if 4 out of the 6 whippets I have owned and I have it. All the females on my mother's side have thyroid disorders - I feel jinxed! I hope the greyhound and two Italian greyhounds don't develop it.

[guysgrams in reply to TSH110]

I hear ya. There is thyroid disease on both sides of my family! I just read an article on hypothyroid dogs and another symptom is sudden aggression when the dog is normally docile. Would not have ever thought that. My other cocker spaniel has just started showing signs of aggression where she never did before so might have to have her tested too. She is 'related' to the other one so... She is 12 also and for the most part never had any issues that way. She has all those fatty lumps everywhere though and has had to have huge ones removed twice in the past three years. My hypo cocker showed signs long before it even clicked with me but after doing some research I suggested to the Vet of the possibility and she said no it wouldn't be that. I told her how she was always looking for a blanket to be under -just like me and asked to have the test done. She was shocked when the results came back. So even with the dogs you sometimes have to fight.

[TSH110 in reply to guysgrams]

Oh gosh they do say aggression can start up with it I certainly became very belligerent in the latter and serious stages of my hideous downfall with hypothyroidism. None of mine showed aggression at all but I remember I looked at The daughter one day flopped down all exhausted and looking so sad and though - you know I feel just like

Her- and I instantly knew she was hypothyroid. I did some research and was very shocked as to how many symptoms she was displaying. The vet was happy to do the tests (so no fighting needed there good job, my aggressive phase had subdued by then - they cost up to £130 a pop so the vet will surely get a cut - so why would they object it is hardly a highly invasive and awful procedure getting some blood out!? And a darn sight better than leaving them to suffer if they are hypo) which came back positive for hypothyrodism.

[guysgrams in reply to TSH110]

All of her ailments with skin, itching etc was chalked up to allergies. Vet probably didn't like the fact that I was researching, not sure. She said her temp was fine! Dog had had problems for so long and nothing seemed to help her. Right before my suggestion the dog had very little hair left on her topside and she had these patches on her skin everywhere and she stunk to high heaven, poor thing. I was really at my whits end. I couldn't keep going back over and over again and have nothing fixed. Vet bills were/are astronomical and so are the tests and the meds they give them. Told the Vet didn't have the money for the continuation and didn't know what I was going to do but I knew my dog was sick. The dog still isn't like I think she should be but she is getting up there.

[TSH110 in reply to guysgrams]

Those are all hypo symptoms. Mine had good fur but greasy and a big bald patch on her tail with black skin - always a sign of it. She smelt bad too she had an endless season poor thing and it can make their breath stink (same in people) she used to gobble up her food at an alarming rate and simple grab the nearest dog bowl and run with it and hide and scoff that food and carry out raiding the others' bowls until they had finished - there were trails of food everywhere. We thought it was funny but now I feel bad because it was a sign that something was seriously wrong. I used to get so hungry I could have eaten the tables! I'd scoff 3 massive meals one after another and still feel famished At least I could cook up more grub but all she could do was steal someone else's - god it is pitifully sad. Have you thought of switching vets to one who is more sympathetic to the dog's continuing problems and is better clued in on the condition? I found NDT (ThyroidS) suited mine better than the version of levothyroxine they were given by the vet. It is very inexpensive. They need more than us about 10x I think (I guess by body weight) and use it up much more rapidly. Might be worth considering? 120mcg NDT= c. 125 mcg Levo and you can swap it slowly to check it is all going ok. Just a thought

This info about testing seems pretty good perhaps you could request the results and see if they are all in order. If anything is not you could bring it up and show her the article

hemopet.org/clients/14145/d...

[guysgrams in reply to TSH110]

Thanks. I did switch vets and will have to look back at the labs to see for sure what all was tested this last time. Our dog has been on the same dose since she began her treatment.

[TSH110 in reply to guysgrams]

Ha ha all

Mine get under the duvet at night a couple of them overheat and emerge hours later huffing and puffing from under the covers they cool off and 10 minutes later burrow back under for another roast!

[guysgrams in reply to TSH110]

Yup!