Effect of T4/T3 combination compared with T4 only

[diogenes]

This interesting paper examines differences in outcome on patients given either T4 only or combined therapy. It shows that potential markers for treatment were better in combination than in mono therapy. To get adequate therapy, TSH was lower in the T4 treatment than in combination. Markers such as rT3, SHBG, and LDL cholesterol/total cholesterol were more suitably placed in their ranges. SHBG higher, cholesterol/LDL lower. T4 would be expected to give lower TSH because conversion has to be carried out.

May 2022 Journal of Thyroid Research 2022(8):1-10

 DOI: 10.1155/2022/6423023

 Betty Ann Bjerkreim, Sara Saleh Hammerstad, Hanne L Gulseth, Erik Fink Eriksen

Abstract

Background: Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5-10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms.

Methods: Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods.

Results: Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups.

Conclusion: We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.    

[Musicmonkey]

Thank you diogenes Much appreciated.

[Musicmonkey]

I'm not sure how administering T4 gives a lower TSH than giving T3...

[diogenes Remembering in reply to Musicmonkey]

Because the same T4 and T3 have different outcomes. 1) you've lost your thyroid. 2) you take T4 only. 3) your active thyroid produced both T4 ad T3, the T3 part helping out in conversion by the body. Therefore you must take more T4 to get the adequate T3. 4) you take T3 only. This is a direct supply to tissues without conversion. Therefore a given amount of T4 must suppress TSH more than the same amount of T3.

[Cup-cake7 in reply to diogenes]

if you still have intact gland why are you given t4 which was near top,of,range naturally anyway 🤔 T3 being at bottom of range (poor,conversion )

Why not just take t3 to help?

I never got clear on this

Many Thanks

[SarahJane1471]

Great findings 👏. But does the small number of participants mean this study will be ignored 🤷‍♀️

[helvella Administrator in reply to SarahJane1471]

We see all too many studies on small numbers accepted when it suits.

Galileo only needed one telescope held to one eye to prove the principle.

[diogenes Remembering in reply to helvella]

Yes, but from all the little acorns, one will sprout and encourage the rest.

[Gingernut44 in reply to diogenes]

Of course, that depends on who’s running the show!

[HowNowWhatNow in reply to SarahJane1471]

if any academic or doctor wants to argue with its findings because of alleged “statistical insignificance” of small study group, they can always repeat the experiment with a larger number of people… if they care for patient outcomes and not just throwing stones

[Lotika]

A few thoughts: - I note that they use an equivalency of 15 mcg T4 to 5 mcg T3, which would equate more accurately with how my body experiences T3 than the standard 25 to 5 dosage ratio; as they point out, the 15 / 5 is more up to date in terms of research than 25 / 5.

- They dose T3 x 3 daily, advising that patients have T3 30 minutes before eating or 2 hours after a meal (30 minutes before breakfast for T4)

- It is curious that they are testing TSH and adjusting dosages so that patients remain within a target TSH reference range of 0.1 - 1.5 (they are working with a range of 0.5 - 3.6) so they're still taking a TSH-centric approach but I assume, wanting to make sure that low TSH is taken off the table as a cause or effect

- They collect trough serum results, so 24 hrs after T4, and 14 hrs after T3

The conclusion if it is helpful for anyone:

Our study demonstrated an improvement in cardiovascular risk factors such as SHBG and total and LDL cholesterol in patients with residual hypothyroid symptoms when treated with LT3 compared with LT4 without differences in NT pro-BNP levels. Also, LT3 did not increase bone turnover. Moreover, we consider the increase in rT3 levels on LT4 treatment an important factor leading to reduced intracellular levels of T3 and residual hypothyroid symptoms despite normal peripheral TSH values. However, future studies are needed to assess the efficacy and safety of long-term LT3 monotherapy.

Can be read for free here: hindawi.com/journals/jtr/20...

I get the impression that they did collect some QoL data from the patients, but given that it's not what the article is about, they don't report those. I'd be curious to know how the patients felt... Apparently 16 reported adverse effects on LT4 mono and 17 on LT3 mono, but that's all we know.

[Tythrop]

Diogenese I was just wondering if the scenario of a downregulation of TSH following,say, an extreme hyperthyroidal episode has been factored into the possible explanations ? As I understand it ,if downregulation of tsh has taken effect the TSH reading becomes meaningless ??

[diogenes Remembering in reply to Tythrop]

The main trouble with interpreting thyroid function (or more exactly, change in thyroid function) by TSH is that there is a considerable lag in TSH change either up from low values in hyperthyroidism from the start of treatment or down from high values in treating hypothyroidism. These lags can be over months depending on how long someone has suffered hyper- or hypothyroidism. Also TSH is its own worst enemy in that it is very sensitive and hasn't a close relationship with FT3 the active hormone, but is influenced more directly with FT4.

[Tythrop in reply to diogenes]

If only NHS would listen to you and scrap TSH tests ,and just go for T4 and T3 ,and maybe the antibodies too