A paper on the approach to optimization of hypothyroid therapy including combination therapy.

[diogenes]

This new paper (downloadable) examines the problem of trying to optimally prescribe thyroid hormones for hypothyroidism. It's very technical, but the conclusions may be of interest. It uses a modelling system to try to gain an insight into good prescribing.

Front. Endocrinol., 24 June 2022

 doi.org/10.3389/fendo.2022....

This article is part of the Research TopicMechanistic, Machine Learning and Hybrid Models of the ‘Other’ Endocrine Regulatory Systems in Health and Disease

. Optimal Hormone Replacement Therapy in Hypothyroidism - A Model Predictive Control Approach

[helvella Administrator Thyroid UK]

It seems that identification of genetic variations could contribute significantly to treatment.

However, the paper is necessarily limited to currently known, recognised genetic variations. Other variations could also be important but might not be readily identified. If this is formalised into guidelines on the basis of these specific variations only, we could continue to see poor treatment in those who have other variations of other genes.

The non-availability of suitable dosages has long appeared a problem. We have got as far as 5 microgram dosages being more available. Do we need to go on to even lower dosages? Especially if split dosing. I suspect so.

Given the concerns about levothyroxine, especially in higher doses and at higher blood levels, and the possibility that there is some link to cancers, isn’t reducing levothyroxine by adjusting medication regimes to include liothyronine, of considerable interest and possible importance?

To me, this work cries out for as near as possible automated continuous testing. If starting on four days at 400 micrograms is good for most, we are sure to find some for whom it isn’t good. Being either still not enough, or too much.

How far away are we from using this model (or any other reasonably good version), near-continuous testing, and fully flexible L-T4 and L-T3 dosing, in real patients?

We might find that using such an intensive approach for a few weeks or months would set someone up for a more relaxed but still effective approach into the future.

We might also find that a non-oral approach to delivery would be of huge benefits. For what this sort of approach leaves out is the effect of thyroid hormones in the gut. And the issues of separating levothyroxine (at least) from food.

[Kit_Monster in reply to helvella]

Really interesting points Helvella.

I have been thinking that our endocrine system is incredibly dynamic, with the varying energy demands. I don't feel that the test themselves and the tests ranges reflect this and individuals experiences.

Wouldn't it be great if there were on demand monitoring of thyroid hormones (like there is for glucose monitoring) where, over time you could build up an individual picture of what's right for you??

And a model where you could include all your data (intolerances, genetic make up etc) which would then help devise an appropriate treatment plan??

At the moment, quite a lot of it is an initial shot in the dark, and then working from there.

Totally agree re delivery method of thyroid hormone replacement. There are already insulin pumps out there for direct injection for diabetes and have been for at least 8 years. Why not for thyroid hormones??

[helvella Administrator Thyroid UK in reply to Kit_Monster]

I think the prime reason is cost.

From something like a pound a month to possible that or more every day is a big reason to avoid considering it.

At present, I think a microneedle array seems the most feasible non-oral approach.

[marigold22 in reply to helvella]

Whole genome sequencing is definitely needed. I was very unwell for 35+ years until I discovered the two vital polymorphisms I carry. DIO2 and MTHFR. Thyroid patients can go around in circles for decades until their genetic variations are uncovered