Study examining liquid/soft gel T4 therapy against solid tablets

[diogenes]

This study has concentrated on bioequivalaence of soft gel and liquid T4 formulations but also remarks on solid tablet T4 uptake and fasting. Not a great paper but I simply append the summary to show their conception of how to take T4 in its various forms:

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

January 2020 International Journal of Endocrinology 2020(10):1-5

DOI: 10.1155/2020/4524759

Pierpaolo Trimbol, Lorenzo Scappaticcio, Annamaria De Bellis, Luca Giovanella et al

Abstract

Objective: Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods: Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. Results: 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86-2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10-2.17) in those on SG/LS (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.66). Conclusion: The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.

[Star13]

"suggest that LT4 SG/LS should be regarded as first-line therapy"

Er.... what LT4 therapy are they suggesting, the tablets or the "non-solid"?

After all wasn't that the point of the study? It wasn't to confirm that LT4 per se should be used because they didnt and are not comparing it with anything else!

[helvella Administrator Thyroid UK in reply to Star13]

That means soft gel (SG) or liquid solutions (LS) should be the first-line therapy.

[helvella Administrator Thyroid UK]

The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy.

Does that sentence have any meaning? If there is no influence by how it is used, what defines "correct" and "incorrect"? Surely there is no distinction if how it is used has no influence?

waiting for at least 30 minutes before breakfast.

Assumption Alley. Why assume any levothyroxine will be taken before breakfast?

And how long does the first-line approach go on for? A week? A month? A year? Forever?

[jimh111 in reply to helvella]

I think they are saying that with liquid or soft gel LT4 it doesn't matter if you take it 30 minutes before breakfast (correct use) or just before breakfast (incorrect use). As English isn't their first language I'm not too bothered although the peer reviews could have made a helpful suggestion.

More importantly their study does not confirm this statement, see below.

[Thyb]

My Endo/GP reckon the liquid levo can be taken either half an hour before food OR 'just before breakfast' Or 'in the evening'.

Personally, 'starting to titrate dose upwards since Only yesterday', I now take 2.5mls in the Morning AND wait an hour before having milky tea, then 2mls in the Evening between 8-10 (I'll wait a couple of hours after I've eaten), hence, time fluctuation.

Previously, I took 1.5mls in Morning and 1.5mls in the Evening (only for the past week), before that I took 2.5mls in the Morning Only.

The only reason I have decided to split the dose am and pm is because I didn't want the awful palpitations/hot sweats that Tirosint gel capsules gave me (25ug).

So far, touch wood, I am not experiencing side effects from the liquid that I most definitely had loads of on the t4 tablets.

I also had an E mail yesterday regarding a yellow card complaint I wrote regarding Accord tablets. 'They' have taken certain batches off the shelves'.

I will have 'Endo's' blood test at the end of the Month plus Medichecks both on the same Day. Only when I see the results will I know if liquid levo works for me (Medichecks includes vits, TSH, FT4, FT3 Etc etc

Here's hoping...Albeit, I will need to titrate the dose slowly upwards until my Ft4/Ft3 are at least mid range

😀😀🙂🙂

[helvella Administrator Thyroid UK in reply to Thyb]

Always good to read of improvements.

Do you have the batch numbers?

[SlowDragon Administrator in reply to helvella]

helvella are you going to investigate this Accord batch issue further

We have had quite a few members report problems recently

[Tythrop in reply to SlowDragon]

And to think "they" object to Armour on the basis of dose issues.

[helvella Administrator Thyroid UK in reply to SlowDragon]

I will do some more checking around.

[Thyb in reply to helvella]

From [e-mail]. Accord Levothyroxine 50mcg Tablets PL 00142/0104, Batch TA1908,

File number opened - MDR 226-09/20

[Thyb]

I just want to say A HUGE THANK YOU TO THIS SITE! Without it I would have been stuck on 50mcg tablets (same for years), and not known that TSH around 4.1, ft4 12-12.2 isn't optimal, albeit literally Just within lab ranges!!

[jimh111]

Thanks for highlighting another sloppy thyroid study!

The doses were not titrated to give similar TSH levels, indeed the difference had a very high degree of significance p=0.0033.

The conclusion 'patients taking LT4 SG/LS had a significantly lower TSH than the tablet group' is correct. This might be because liquid levothyroxine is better absorbed. It could also be that it is less stable and a higher dosage is used to keep it within the usual 90% - %110 range. It could be that some of the patients had large teaspoons or measured out slightly more just to make sure they were getting a full dose. I'm suspicious that the liquid and softgel results were not reported separately.

Doses should have been adjust to obtain similar TSH levels.

The statement 'in the SG/LS group, TSH remained stable when therapy was incorrectly taken' is incorrect and contradicted by the words that follow 'and lowered when therapy was correctly followed'. Either it made no difference or it did. (See below for an explanation why the above is incorrect).

'On the contary, patients on LT4 tablet had a significant increase of TSH levels and nine percent of them lost the euthyroid state'. This again is incorrect. I assume the latter means TSH went above their definition of euthyroid which they don't reveal. The tablet group had higher TSH levels and so are more likely to have some patients with an elevated TSH.

The big mistake is not considering the consequences of the two groups having different TSH levels and not taking this into account when doing the mathematics. TSH increases exponentially as thyroid status (fT3 and fT4) falls. When comparing the effects on TSH we must look at ln(TSH), not scaler TSH.

Incorrect tablet therapy reduced ln(TSH) by ln(2.30) - ln(1.67) = 0.321.

Incorrect SG/LS therapy reduced ln(TSH) by ln(1.24) - ln 0.80) = 0.438.

Incorrect use of SG/LS therapy had a greater adverse effect than tablet therapy! It's unlikely these results are significant. It would have been better to equalise the two groups rather than have to make mathematical corrections.

This study shows that SG/LS therapy had no benefit in these patients. A subsection of patients with gut problems derive great benefit from liquid levothyroxine. More would benefit from T3.

As an aside I've noticed that if I put a levothyroxine in my mouth before I've got a drink it has usually dissolved by time I get a swig of water or glass of orange juice. It would be interesting to see what effect keeping a tablet in the mouth for 10 seconds has.