Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review +

[helvella]

Over the years there have been many mentions of the possibility of once-a-week dosing with levothyroxine. I have always found it questionable. Seemed to be justified solely for the convenience of the person attending the patient - such as a district nurse.

Last sentence of conclusion:

Hence, OWT may not be the safest way to correct hypothyroidism, especially in elderly (for whom such a regimen was originally devised) with underlying cardiac disease.

Which doesn't sound good.

It is appalling that this has been promoted in various ways for so many years without any proper evidence. Again, I quote:

it may be said that this first meta-analysis on the efficacy and safety of OWT

Indian J Endocrinol Metab

. Mar-Apr 2021;25(2):76-85.

doi: 10.4103/ijem.IJEM_789_20. Epub 2021 Sep 8.

Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis

Deep Dutta 1 , Radhika Jindal 2 , Manoj Kumar 3 , Divij Mehta 4 , Anil Dhall 5 , Meha Sharma 6

• PMID: 34660234

• PMCID: PMC8477739

• DOI: 10.4103/ijem.IJEM_789_20

Abstract

Aims: No meta-analysis is available which has holistically analyzed efficacy and safety of once weekly thyroxine (OWT) vs. standard daily therapy (SDT) with regards to managing primary hypothyroidism. We undertook this meta-analysis to address this knowledge gap.

Methods: Electronic databases were searched for clinical trials involving hypothyroid patients receiving OWT in intervention arm, and SDT in control arm. Primary outcome was to evaluate changes in serum thyroid stimulating hormone. Secondary outcomes were to evaluate alterations in total tetra-iodothyronine (TT4), total tri-iodothyronine (TT3), free T4 (FT4), free T3 (FT4), heart rate (HR), cardiac function, symptomatology, and adverse events.

Results: From initially screened 159 studies, data from four trials involving 294 patients were analyzed. Patients of OWT had significantly higher thyroid stimulating hormone (TSH) [mean difference (MD) +1.85 mU/L (95% confidence interval, CI: 0.95-2.75); P < 0.01; I 2 = 63%], comparable TT4 [MD -0.87 mcg/dl (95% CI: -2.98-1.24); P = 0.42; I 2 = 65%], and significantly lower TT3 [MD -15.7 ng/dl (95% CI: -29.9-1.51); P = 0.03; I 2 = 90%], following 6-weeks therapy. TT4 [MD 3.05 mcg/dl (95% CI: 1.44-4.66); P < 0.01], and FT4 [MD 0.56 ng/dl (95% CI: 0.04-1.08); P = 0.03; I 2 = 66%] were significantly higher 2 h after thyroxine intake, in people on OWT compared to SDT. TT4 levels were significantly higher 4 h after thyroxine intake in OWT as compared to SDT [MD 0.70 ng/dl (95% CI: 0.52-0.88); P < 0.01]. Following 4-8 h of intake of thyroxine, isovolumetric contraction time [MD 3.62 ms (95% CI: 1.93-5.31); P < 0.01; I 2 = 0%] and aortic ejection time/pre-ejection period ratio [MD 0.01 (95% CI: 0.00-0.02); P = 0.02; I 2 = 0%], were significantly higher in people on OWT as compared to SDT.

Conclusion: OWT is associated with less efficient control of hypothyroidism at 6 weeks and may be associated with supraphysiologic elevation of thyroid hormone levels along with transient echocardiographic changes in some patients following 2-4 h of thyroxine intake.

Keywords: Daily thyroxine; hypothyroidism; weekly thyroxine.

pubmed.ncbi.nlm.nih.gov/346...

Full paper open access here:

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

[helvella Administrator]

I think this means we should not consider once-weekly dosing as an acceptable practice.

[tattybogle in reply to helvella]

i'd always assumed it didn't actually happen very often ..so i'm surprised by how many cases they found to review .. i thought it was only really used in eg psychiatric cases where getting people to agree to take it regularly was impossible . Am quite appalled if they have been giving a whole weeks worth to elderly people in nursing homes .

[nellie237 in reply to tattybogle]

I assumed the same as you.

[helvella Administrator in reply to tattybogle]

Practice in India could be somewhat different.

Though I first read about it in relation to the UK and specifically visiting healthcare people as it avoided the need to visit every day.

[diogenes Remembering]

Once weekly T4 dosing is a red herring. Imagine you take the weekly dose in one go. The halflife of T4 is about a week. So by the end of the week the patient will move from above-normal T4 levels to half the levels (if you want to achieve acceptable FT4 levels at some time during the week). So for the first half week the T4 levels will go from an elevated dose to about normality. But then the T4 will diminish to half that and will be inadequate by the time the next dose is given. Once daily avoids this big oscillating change because a suitable T4 dose is given each day and peaks will not occur nor will troughs.

[janeroar]

I’m shocked this is even considered as a possible treatment. Underlying it I think is a deep lack of compassion and care for people that is prevalent in some medical circles. Psychiatric patients - who seem to be a significant number of the people who receive once weekly dosing - need more than any other section of the population the utmost care when it comes to hormone medication. Thanks for posting helvella.

[tattybogle in reply to janeroar]

good point . i wouldn't fancy my 787mcg Levo all at once on a Monday morning , even if my brain chemistry was tickety boo .. i certainly would fancy it if it wasn't. And i imagine the following weekend would be no fun at all.

[janeroar in reply to tattybogle]

Yes beggars belief it’s even being considered.