This newly out paper discusses the benefits of combination therapy over T4 therapy in several situations. It seems that some mutations favour combined therapy whilst others favour T4 only
Front. Endocrinol., 24 June 2022 | doi.org/10.3389/fendo.2022....
Optimal Hormone Replacement Therapy in Hypothyroidism - A Model Predictive Control Approach
Tobias M. Wolff1*, Johannes W. Dietrich2,3,4 and Matthias A. Müller1
In case this is of any interest to other members - have you had a 23andme genetic test?
My 23andme genetic test (from almost exactly seven years ago) included both polymorphisms mentioned in the Conclusion. Earlier, or later, 23andme analyses might not include them, or only some of them. (Which means, check they are still included if you have been considering doing a genetic test.)
Similarly, you might find them on genetic tests offered by other companies.
I found them by going to my raw data and searching for the rs... numbers.
DIO1 rs2235544 A / C
DIO2 rs225014 T / T
(Edited 11:57 25/05/2022 to remove inadvertent duplicate.)
This company with turn the raw data into easy to understand info
At a cost! 
£15 in 2020
Is this a typo? Currently £139 mthfr-genetics.co.uk/DNA/
That’s the cost of full test
If you already have test results from Ancestry, 23 and me or other companies it’s a small cost to get these tests evaluated (presumably just run through a computer program)
£15 in 2019
Ah I see, my mistake.
This sounds much better than the company I initially used that just churned out thousands of pages of interpretations.....
Probably explained by the fact that it cost just a few dollars !!
I started working my way through that lot but decided I'd need to live to at least 200 without ever leaving the computer to reach the end!!
Going over to your link now...
Thank you again SlowDragon .
Wondering...did you find much related to the thyroid/hypothyroidism in the Lifestyle Genetics report.I get the impression they are tending towards "nutritional genomics"
Maybe just my weak, faltering steps into this hefty subject!
Thank you.
I already had done Dio2,gene test via regenerus
It showed lots of generic issues re low vitamin D
Low vitamin D and autoimmune often go together
Ambiguous re coeliac (but again already knew that from NHS gene test after my endoscopy confirmed gluten intolerance )
One gene out of three linked to hemochromatosis,
Was interesting as I have had high ferritin long time.
Was worth the £15
Thank you
I had the Dio2 test a few years ago....homozygous.
My Vit D was 17 when I started out on my thyroid journey...interested to see what the genes say! It's optimal now.
I've just received the results from the raw data so time to digest those
It does seem to be a lot of information for the money but I guess it's part of their research too.
My vitamin D was 12…..unfortunately no one told me or prescribed vitamin D
Me neither...years ago one of my daughters in law had been reading an article about Fibromyalgia (I'd just been diagnosed and wasn't convinced!) she saw vit D mentioned....she mentioned I should have a test and pursue it.
The first two you give in your list seem to be the same ones but you mentioned three polymorphisms. 🤔 perhaps it’s the possible combinations you are referring to?
I get A/C & C/T
You are absolutely right - I was too busy looking for next, doing copy and paste to look up - and missed that the same SNP is mentioned twice!
Very useful, thank you!
Oh goodness, I have that defective gene in DIO1 and the one in DIO2. Yet according to this, my body prefers both Levo monotherapy and Combination therapy! Typical of me to be awkward!
I really wouldn't call it "defective" - it is just one of the panoply of variations we all have.
The word defective seems to do what so much medicine does, blame the patient.
If we wander though genetic history, we'd find lots of variants that appear and disappear over the millennia, and longer. I suspect that for most which don't actually stop us reproducing, one way or another, we might find it difficult to determine whether a particular polymorphism is a "good thing", a "bad thing", or just "one of those things".
The discovery of a genetic variant indicating T3-only ( supraphysiological dose) as the appropriate treatment would welcome!!!
Very useful research. It may be that people with polymorphisms have slightly different ideal hormone profiles, they may be genetically adapted to small variations in hormone levels.
I think the greatest benefit of this work is understanding how the axis works and being able to more accurately identify when the axis is broken. e.g. if TSH, fT3 and fT4 are all near their upper (or lower) limits something is wrong but patients tend to get told their hormone levels are normal.
Optimal levels need to be established. There’s a danger in taking healthy population levels as optimal. Endocrine disrupting chemicals are ubiquitous, we can’t assume they have not distorted hormone levels.
An important factor is evidence that lower fT4 levels are associated with a longer and healthier life, higher normal fT4 is associated with cancer and cardiac disease. People in the lowest third of the fT4 interval live 3.5 years longer than those with an fT4 in the middle and upper thirds. Currently thyroid therapy is targeted at high normal fT4 (levothyroxine monotherapy) thus putting nearly all thyroid patients into the shorter life group. Given the choice it makes sense to keep fT4 in the lower half of its reference interval by prescribing a little T3 - whether or not the patient needs T3 to feel better. We wouldn’t target cholesterol levels or body weight according to population averages, neither should we target thyroid hormone therapy to population averages if they are found to be suboptimal.
Great work, I hope it can identify as yet undiagnosed forms of hypothyroidism and specifically cases where the axis is broken as in these cases we can’t use the axis (TSH) as a marker for clinical euthyroidism.
Just had cateract done so dodgy reading and brain aches, but my questions ref genes and t4 to t3 convertion are : (1) are there several or just one gene code that adversely impacts on convertion and (2) from a standing start, what is the genetic test company that is best to use ? Thanks
Several I believe. They can occur from Mum & Dad in heterozygous (1 "normal" ie common) form and 1 genetically different or homozygous (both the same (Common or uncommon) or even rarely abnormal heterozygous ( 1 for in one genetic state and the another in another, neither of which are common). Can only really find these by gene sequencing.
Studies on TSH for those on combined T3 T4 therapy 
