A Bizarre Complication of Levothyroxine Therapy

[helvella]

This is rare - a very sensible discussion about sensitivity to different formulations of levothyroxine.

I don't think it is possible to identify the three formulations discussed. India has a fearsome number of formulations available!

Letter to the Editor

A Bizarre Complication of Levothyroxine Therapy

Joseph, Aneez; Cherian, Kripa Elizabeth; Kapoor, Nitin; Paul, Thomas V.

Author Information

Indian Journal of Endocrinology and Metabolism 25(2) 166-167, March–April 2021. | DOI: 10.4103/ijem.IJEM_87_21

Sir,

We describe the case of a 49-year-old gentleman who presented with a generalized urticarial rash with wheals, itching, and angioedema 6 weeks after the initiation of levothyroxine (Brand-1) tablets for hypothyroidism. He was diagnosed with hypothyroidism while being evaluated for carpal tunnel syndrome. His thyroid-stimulating hormone (TSH) level before initiation of therapy was 170.9 mIU/L. There was no history of allergy to drugs, foods, or any other medications before the development of the present allergic reaction. There was no history to suggest chronic urticaria. He discontinued the medication by himself following which his rash subsided with complete resolution of urticarial lesions in 3 weeks. Clinical examination at the time of presentation was unremarkable. On follow-up after stopping the medication, his TSH was 28.3 mIU/L, T4 was 4.4 mcg/dL, and free T4 was 1.1 ng/dL. The titers of antithyroglobulin and antithyroid peroxidase were 1226 IU/mL and 705 IU/mL, respectively. Immunoglobulin E (IgE) was 102.2 U/mL (N: 0–378). Besides IgE, antinuclear antibody (ANA), C3, and C4 were done, these were normal. Anti-C1q antibody testing was also negative. He was started on levothyroxine (Brand-2) 12.5 mcg and on the same day developed urticarial rash [Figure 1] that subsided completely after stopping the medication. Subsequently, he was initiated on 12.5 mcg of levothyroxine (Brand-3), which he tolerated well, without the development of allergic reactions. It was decided to gradually increase the dosage of levothyroxine over the next 4 weeks.

The annual incidence of hypothyroidism is 1 in 10,000 in males and 1–2/1000 in females.[1] Levothyroxine supplementation is the routinely accepted treatment for hypothyroidism worldwide.[2] There are previous cases of thyroxin allergy that have been reported.[34] Allergic reactions to thyroxin may be due to its active ingredient or other chemical excipients. The active ingredient in thyroxin tablets is levothyroxine sodium. In addition to this, there are several inactive ingredients that vary from brand to brand. A few of the common inactive ingredients are microcrystalline cellulose, maize starch, purified talc, colloidal anhydrous silica, magnesium stearate, lactose, and acacia.[5] Our patient did not develop an allergy to Brand-3 of levothyroxine and hence the probable causative agent could be one of the inactive excipients. Drug desensitization under supervision with gradual uptitration of the dose may be done as a treatment option in patients who develop recurrent allergic reactions to different brands of thyroxine.[6]

Full text open access - including other details such as photo - at both links:

journals.lww.com/indjem/Ful...

europepmc.org/article/MED/3...

[HealthStarDust]

Thanks for posting this. Confirms what many think of many drugs and not just levothyroxine. So often the orginal first brand of a drug at least causes the least amount of harm, generally, then come the the brand generic aka rip offs. Big Pharma.

[helvella in reply to HealthStarDust]

When it comes to levothyroxine in the UK, I'm not convinced.

What has been the reference branded product, Eltroxin, contains both acacia and lactose. Two substances which seem to cause issues for quite a number. Despite seeming to be lactose tolerant in every other way, I much prefer three out of the four lactose-free formulations I have tried. (Not Teva!)

And levothyroxine and liothyronine have never been patented so that aspect simply doesn't hold.

[HealthStarDust in reply to helvella]

Ah. I would have to agree in that case.

[SlowDragon Administrator]

Not that bizarre at all ……just most medics think we are “making a fuss” requesting certain brand of levothyroxine

Many, many members find that they can’t change brand of levothyroxine, or may only tolerate one brand of tablets

And small minority have to have liquid levothyroxine

[helvella in reply to SlowDragon]

I agree it is not at all bizarre.

But hoped that a report such as this, even though there is widespread "not invented here" syndrome at play, especially with respect to non-western countries, just might help someone to backup their own intolerance issues.

[SmallBlueThing]

A shame they didn't get to the bottom of the problem, to save the patient from potential issues with other medicines.

Excipient problems are discussed at: mastcellsunited.com/2020/02... -- I was interested to see the claim regarding cotton vs. wood sources of microcrystalline cellulose. (Edited to add: I don't hold with that author's "natural" stance.)

I had hives popping up during my sleep after the second intramuscular dose of the antibiotic teicoplanin. It was the night before the monitoring blood test, and the on-the-ball phlebotomist spotted a patch on my upper arm. Teicoplanin is frequently used during surgery, so I hope my medical record gets read, should I ever need to go under the knife.

No hives, but my veins seemed to "pop" at the sites used for monthly plasma donations, when I first started taking levothyroxine. I've read of thyroid hormones being important for vascular integrity.

[helvella in reply to SmallBlueThing]

It would have helped if they had specifically listed the ingredients of each of the three he took!

A great pity the paper referred to by your link is behind a severe paywall - only the abstract is accessible:

pubmed.ncbi.nlm.nih.gov/311...

[SmallBlueThing in reply to helvella]

I took a quick look at the paper at a certain "hub" and levothyroxine is only mentioned in passing, in the Abstract.

I'm a "second liner" for Eltroxin on my prescription, so Lloyds Direct (and the rest) ignore it. I think I'm less troubled by the crusting type of rhinitis, since being on Accord's levothyroxine which, as you know, doesn't contain acacia. The practice pharmacist is due to 'phone about reducing my dose, and I'll suggest alternating 150/100 mcg instead of taking 150 mcg daily, to avoid the risk of receiving Teva 25 mcg tablets.

[Batty1 in reply to SmallBlueThing]

How do you know its the thyroid meds giving you rhinitis? I have been dealing with sores inside my nostrils for at least a year can’t figure out the cause.

[SmallBlueThing in reply to Batty1]

My previous GP was supposed to be the ENT for the practice, but showed no interest, after getting me tested for vasculitis. Other meds I take can cause stuffiness, but I've not had any crusting since I've been on Accord's levothyroxine, I think. Best of luck with yours, as mine certainly worsens my sleep apnoea.

[plumpot]

I had this when on Levo, I take NDT now.

[Batty1]

I feel for this patient I landed in the emergency room with hives as big as saucer plates even the emergency room doctor said he never seen anything like it I had 5 hives on top of each other all over my body I looked like the Elephant man “acacia” is poison.

[asidist]

Thank you helvella. It was actually an extremely helpful posting or comment you had made years ago about allergic reactions to levothyroxine sodium that helped me validate my own experience of having an allergic reaction (primarily body-wide hives and angioedema) to exogenous T3 itself, despite having no allergic reaction to any formulation of levothyroxine. The allergic reaction to liothyronine occurred with every brand I tried, including compounded liothyronine with only one other excipient, as well as ndt, and it occurred when trialing T3 formulations at diagnosis of hypothyroidism (after which I gave up on T3) as well as almost a decade later when trialing the formulations again.

Just an illustration of an allergy to the exogenous hormones themselves. For me it was very, very difficult to navigate because even though there are documented case studies about allergic reactions to levothyroxine (thank you so much for linking me to those back then😌) and pre-formulated levothyroxine sodium solutions to use for desensitization procedures, there are none at all for allergic reactions to liothyronine, and it took quite a lot of effort to get my allergists to even accept that was what was happening, let alone get help for it.

FWIW, thankfully the permanent resolution of the hives and angioedema turned out to be a simple and accessible protocol in my case, though it frustratingly took almost a year of dealing with the allergy and various allergists to come across it: Taking higher dose antihistamine DAILY (no skipping days, despite the relief from each antihistamine dose lasting well beyond 24 hours) for 4-5 months (I did five). The consistent, continued use of higher dose antihistamine apparently can permanently affect the reactivity of skin mast cells or some such - unfortunately I can no longer remember exactly how my allergists explained the mechanism behind this protocol. (Because I have other ongoing difficulties with thyroid treatment, do sometimes wonder if there might still be some sort of ongoing complex allergy/immune issues at play that weren’t resolved by the antihistamines, but have not found any way or help to investigate that possibility. I’m inclined to believe that resolution via desensitization, when possible, might be a better/more comprehensive route to take.)

Note: I collected a lot of research about / related to this when dealing with it, so if anyone else is dealing with this or looking for resources, feel free to message me.