Efficacy of subcutaneous Levothyroxine in a case of refractory hypothyroidism: A case report

[helvella]

If it works, seems very reasonable!

Medicine (Baltimore).2022 Jul 1; 101(26): e29690.

Published online 2022 Jun 30. doi: 10.1097/MD.0000000000029690

PMCID: PMC9239661

PMID: 35777000

Efficacy of subcutaneous Levothyroxine in a case of refractory hypothyroidism: A case report

Annabelle Naman, MD,a,b Brigitte Delemer, MD, PhD,a,c Didier Marot, PharmaD, PhD,d Elise Michelet, PharmD,e Bénédicte Decoudier, MD,a and Sara Barraud, MD

Rationale:

Daily oral synthetic levothyroxine (LT4) is the main treatment for hypothyroidism, which, in most cases, allows the regression of symptoms and the normalization of the thyroid function. However, rarely, despite a high dose of oral LT4, hypothyroidism persists and is called refractory hypothyroidism. Intravenous or intramuscular treatment is then often necessary. We report the case of a patient with refractory hypothyroidism successfully treated with subcutaneous LT4.

Interventions and outcomes:

After 4 weeks of weekly intravenous injections of 200 µg LT4 in complement to the oral treatment, thyroid balance was improved (TSH: 21.8 mIU/L). We tested the replacement of intravenous with subcutaneous injections of LT4 and gradually increased injection frequency from 1 to 3 injections per week (600 µg/week). Simultaneously, oral treatment was gradually tapered off, and within a few months, thyroid function tests were normalized. Two years later, hormone levels remained normal without symptoms of hypothyroidism. The only side effect was a local reaction in the first few weeks of injections, which spontaneously resolved.

Lessons:

In this case of unexplained oral LT4 malabsorption, subcutaneous injection allowed a self-administrated physiological dose of LT4 3 times weekly. Considering the efficacy of subcutaneous injection of LT4, this treatment could be a safe and easy alternative for patients with malabsorption.

Keywords: hypothyroidism, levothyroxine, refractory hypothyroidism, subcutaneous

Full paper accessible here:

ncbi.nlm.nih.gov/pmc/articl...

[diogenes Remembering]

Actually, there is nothing wrong with this approach, but of course it is somewhat more difficult to see it as routine for all (eg additional injector costs of throwaway needles and tubes). Logically, injection bypasses the vagaries of intestinal absorption and food interference. It could be looked at as a very close relative of direct thyroidal hormone production into the bloodstream from the gland, with the proviso that control and response is limited to what is injected. It only differs from gland output in that it is in a new place in the bloodstream.

[helvella Administrator in reply to diogenes]

I think many of us have had a mental picture of an implementable device that does this - squirt out some thyroid hormone - whether on a schedule or in response to some more complex algorithm. (Or even with the possibility of the person themselves doing something to make it release a little more, if they feel it is needed.)

Is it possible that there are some bacteria which can use levothyroxine, even liothyronine, as a substrate?

[diogenes Remembering in reply to helvella]

If as I suggested many moons ago a motorised vein attached injector was invented, it could save a lot of worries about timing etc and separate T4/T3 chambers might be possible, with a warning signal when supplies are running out. The trouble is that compared with simply taking tablets by mouth, the upfront cost of injector production is still a mental block for progress. Plenty f bacteria will eat T4 or T3. The backbone is a tyrosine derivative which is easily recognised.

[TSH110 in reply to helvella]

I had one of those contraceptive five rod things in my arm for some years, could anything like that be devised? Not much control over dose tho.

[helvella Administrator in reply to TSH110]

Seems to be worth investigating but would take a lot of testing.

[TSH110 in reply to helvella]

I think the dose control might be a major limitation as initially you have to have a higher dose then it tails off after about two years which wouldnt be ideal for Levothyroxine. As far as I know it was one size fits all again not appropriate for Levothyroxine. No doubt these issues could be overcome if they were properly looked into, after all we got men on the moon!

[Serendipity__]

Thank you for sharing, Helvella! Will share with my doctor.❤️❤️❤️

[Poniesrfun]

They never mention what the follow up Free T3 is - only saying TSH and FT4 "normalized". This is a case where I would also want to know Total T4 and Total T3 to confirm it is actually an absorption issue and not a binding hormone issue.

SubQ injection is not a far out thought - I believe in some situations (such as nursing homes with patients who might not be taking oral meds) this has worked.

As far as implantable meds as TSH110 wondered - Bianco used implanted slow release levothyroxine and liothyronine beads in his lab mice (per a recent article).

Doctors/researchers always seem to make a big fuss over the idea of T3 having to be taken multiple times a day (which I am fine with) but also seem to forget that many meds are short actin and need multiple dosing. IMO it's actually an advantage in being able to control our own meds. Thankfully I have a practitioner who doesn't hold me hostage to any fixed dose.

Patti in AZ

[helvella Administrator in reply to Poniesrfun]

Ironically, the anti-thyroid medicine Carbimazole - half-life 3.5 to 5.4 hours - is a classic example. (Or the very similar Methimazole, as used in the USA.)

I agree that short half-life can be an advantage. It is, surely, far worse to take doses of something day after day, it building up, and ending up over-dosed. Then it taking days for the level to drop? Which is towards what happens with levothyroxine.