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Liver Injury Induced by Levothyroxine in a Patient with Primary Hypothyroidism

helvella profile image
helvellaAdministrator
15 Replies

Another perplexing case of a patient suffering liver injury.

This report discusses use of desiccated thyroid and liothyronine.

Again the suggestion that the problem is hapten-based.

Liver Injury Induced by Levothyroxine in a Patient with Primary Hypothyroidism

Tomotaka Kawakami1, Atsushi Tanaka1, Shinichiro Negoro1, Yoshihiko Morisawa1, Masaki Mikami1, Makoto Hojo1, Takatsugu Yamamoto1, Satoko Uegaki1, Mitsuhiko Aiso1, Takahiro Kawasaki1, Taro Ishii1, Yasushi Kuyama1, Toshio Fukusato2 and Hajime Takikawa1

Abstract

We report a patient with primary hypothyroidism, who developed hepatocellular injury due to levothyroxine, synthetic thyroxine. A 63-year-old male was admitted to our hospital due to elevation of liver enzymes. The patient was diagnosed as having hypothyroidism and had been treated with levothyroxine for almost two months until admission. Drug-induced liver injury induced due to levothyroxine was suspected and liver enzymes were rapidly decreased after discontinuation of levothyroxine and dried thyroid powder, also containing thyroxine. Synthetic triiodothyronine, the deiodinated form of levothyroxine was administered instead, and was well tolerated by the patient. The drug-induced lymphocyte stimulation test (DLST) using levothyroxine was negative. Since triiodothyronine which structurally resembles levothyroxine did not cause liver injury, and DLST using levothyroxine was negative, it is unlikely that levothyroxine itself was targeted by the immune system. Rather, we assume that the complex of levothyroxine as the hapten and liver-related macromolecules in the body as the carrier might have acquired antigenecity in this patient and subsequently resulted in liver injury.

Key words: levothyroxine, drug-induced liver injury (DOI: 10.2169/internalmedicine.46.0086)

Open access here:

jstage.jst.go.jp/article/in...

See also these other posts here:

Liver injury induced by levothyroxine tablets in a patient with hypothyroidism

healthunlocked.com/thyroidu...

Occurrence of thyroxine tablet (Thyradin S(®)) - induced liver dysfunction in a patient with subclinical hypothyroidism.

healthunlocked.com/thyroidu....

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helvella
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15 Replies
inthedoldrums profile image
inthedoldrums

Gosh, that is really interesting I will have to put it on the back burner for a while before I read it fully though.

My interest is that in the unpleasant run up to finally being really ill on Levo after 2 years on it., I felt very 'liverish' and could not tolerate oily or fatty foods at all and felt sick a lot of the time. My complexion had a slightly yellow look it seemed too.

It took about six months after stopping Levo for that part of my system to recover and for my appetite to gradually recover. During that time I lost a lot of weight and could only tolerate small light meals like scrambled eggs, mashed potatoes, rice etc.

Maybe another little piece in my jigsaw.

Thank you.

Janine159 profile image
Janine159 in reply tointhedoldrums

I saw my liver test results showed a bit out of the reference range it never ever has been in my life. The lab had recommended a retest be done. But I think as the Dr rang with my results last week and never said anything but your tests are ok .I guess they decided it didn't matter . I have asked about why not retesting. They decide that it's not important I suppose . Why do labs recommend things then it doesn't happen x

Dandelions profile image
Dandelions

sorry if this has already been asked, but do we know which brands contain Hapten?

helvella profile image
helvellaAdministrator in reply toDandelions

Hapten isn't so much a substance as a concept.

Try this:

Beads and a Necklace: A hapten is like a bead—small and insignificant by itself. But when strung together with others on a necklace (a carrier protein), it becomes something noticeable and complete.

Many molecules can act as haptens but only some combinations have an impact. Imagine the bead is yellow and the other beads are red. If someone has been told to look out for a sequence of red-yellow-red, then adding that yellow bead makes a trigger. But only if someone is looking for that sequence. If they are looking for any other colour combinations, adding the yellow to a red necklace will do nothing.

This mechanism lies behind penicillin and poison ivy sensitivities. One brush with poison ivy might have little effect. But a second brush can be serious because the body learned from the first contact.

(Please don't think I know all about haptens. I absolutely do not. I'm struggling to come up with an answer at all!)

Dandelions profile image
Dandelions in reply tohelvella

Hm.. that is very complicated indeed. But makes somewhat sense. Probably due to your clear explanation!

So there isn’t a particular brand to watch out for?

It’s a combination of ingredients and certain bodies ( and their past experiences) meeting in an unfortunate way?

helvella profile image
helvellaAdministrator in reply toDandelions

Yes.

In many ways, the difficulty seems to be that there are many clear, known allergens (and toxins). But if you look through a list, such as the excipients in a medicine, you might not recognise any of them as allergens and toxins.

I'd go further and suggest that many toxins are universal - everyone is susceptible to fugu fish poison, or cyanide. Whereas these haptens can affect some people - but not others. One example is penicillin - some are fine, others cannot tolerate it. And some of us suffer nickel allergy but many don't. Though things like poison ivy work as haptens but affect all of us.

Panda_26 profile image
Panda_26

This is so interesting thankyou . Some years back I was struggling and had really elevated gamma levels on blood tests . This baffled both the endo and my GP and I felt like they must be suspecting I was a secret achololic! We never really found out why except my GP had found a theory that being hyperthyroid can occasionally cause this. And as a thyroid cancer patient I've always been slightly over replaced in terms of thyroid meds as that's the protocol . Fast forward 10 years and liver tests had settled in-between but recently I've had a very raised one again . Have been doing some research again myself so this is all helpful . Will keep reading !

knitwitty profile image
knitwitty in reply toPanda_26

Hi Panda, my son had elevated liver enzymes prior to being diagnosed coeliac. The first consultant we saw laughed me out of her room saying that raised liver enzymes had nothing to do with coeliac disease, despite me having a BMJ article in front of her saying they could be raised with undiagnosed , untreated coeliac disease. She refused to look at the article, however a more senior consultant reviewed the situation and acknowledged that raised liver enzymes can be caused by coeliac disease.

His liver enzyme results returned to normal since becoming gluten free and have remained normal since ( 8 years ).

So maybe get a coeliac test before going gluten free if you are not already gluten free. Good luck. :)

Litatamon profile image
Litatamon in reply toknitwitty

Isn't it crazy how they can dig their heels in on issues that they are not up to speed about? What do they think, research stopped the minute they became a doctor? Or that they have some way of being up-to-date despite their busy schedule, like through osmosis or something. Head banging ways.

Panda_26 profile image
Panda_26 in reply toknitwitty

Thankyou that's interesting, I have had coeliac tests in the past as have often suspected but they've always come back negative. I'm now mostly gluten free as I know I'm mostvlukely intolerant but occasionally slip up so I guess there could be something there ... What a minefield! 🙄

knitwitty profile image
knitwitty in reply toPanda_26

If you are almost gf it will be very difficult to get a positive blood test for gf antibodies because you need to be eating quite. a lot of gluten containing foods for about 6-8 weeks before being tested .

It was just a thought , your liver enzymes may be nothing to do with gluten but I thought it was worth mentioning it. Good luck getting to the bottom of your liver problems. :)

Panda_26 profile image
Panda_26 in reply toknitwitty

Thanks, yes I did that on advice of GP , - ate plenty gluten in the run up to the test . So definitely don't think I'm coeliac but gluten intolerance is a thing for me , and still best avoided !

bluejourney profile image
bluejourney

I thought it was interesting the Levothyroxine they put the patient on that didn’t cause problems. It was L-Thyroxine Berlin-Chemie. I looked up the added ingredients and as far as I can make out they are: calcium bicarbonate, dextrin, glycerate, long chain sodium carboxy, methyl starch, microcrystalline cellulose - none of the excipients people sometimes have trouble with like lactose, maize and mannitol. Also they do handy 25 mcg tablets, useful if you split your dose. I wonder if they are a good alternative to those who want to limit excipients, and if they are readily available in the UK.

helvella profile image
helvellaAdministrator in reply tobluejourney

They are not readily available in the UK. You can find what is available and all ingredients in my UK document. :-)

helvella - Thyroid Hormone Medicines

helvella has created, and tries to maintain, documents containing details of all thyroid hormone medicines licensed in the UK and, in less detail, many others around the world. There is now a specific world desiccated thyroid document.

I highly recommend viewing on a computer screen, or a decent sized tablet, rather than a phone. Even I find it less than satisfactory trying to view them on my phone.

helvella - Thyroid Hormone Medicines - UK

The UK document contains up-to-date versions of the Summary Matrixes for levothyroxine tablets, oral solutions and liothyronine available in the UK. Includes injectables and descriptions of tablet markings which allow identification. Latest updates include all declared ingredients for all UK-licensed products and links to Patient Information Leaflets, Dictionary of Medicines and Devices (dm+d), British National Formulary, NHS Drug Tariff, etc. PLUS how to write prescriptions in Appendix F.

Also includes links for anti-thyroid medicines (but not product details).

📄 dropbox.com/s/bo2jzxucgp9hl...

helvella - Excipients

Details of excipients are in my Excipients document. This includes all excipients identified in UK-licensed thyroid hormone medicines.

📄 dropbox.com/scl/fi/tud6r8f5...

helvella.blogspot.com/p/hel...

If the last updated date of a copy your have downloaded isn’t very recent, please download a new copy!

Blog last updated 11/11/2024 - documents are regularly updated

helvella.blogspot.com/p/hel...

Ninjacaz profile image
Ninjacaz

Hmm. My ALT was very elevated until I reduced my T3 about 4 months ago. Now it’s just a bit high (all other liver markers are normal though). Interesting.

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