Can anybody shed any light on the implications of having Heterozygous TA gene mutation ( my sister) compared to my result of Homozygous type AA? I have standing Hashi’s , had the gene test 2 yrs ago and am now on private prescription T3 monotherapy (50mcg/ day). My sister’s GP thinks her results are ‘in range’ and didn’t really understand the Regenerus labs results letter. Sister has slightly milder symptoms of hypothyroidism. I expect that, in due course, she will see an endo but I am curious if anyone can shed any light on the difference between AA and TA. Does the T represent the Thr92Ala substitute and the A represent the ADRB2 receptor? I have read the explanation and semi-understand it. Thank you!
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Each rung of the DNA ladder has 2 letters of DNA code which bond together in pairs.
A (adenine) and T(thymine) bond together, as do C(cytosine) and G (guanine)
Identical letters (e.g TT or CC) means you either have no genetic variants ( wild type indicated with "+" ) or you have both genetic variants which is what we are interested in here (homozygous/from both parents)
A combination of letters (e.g. CT) means you have one genetic variant (heterozygous/ from 1 parent)
Conversion of T4 to T3 in those who have inherited the snp from both parents (homozygous)is said to be impaired more than if inherited from one parent (heterozygous).
Dio1 is mainly expressed in the liver and kidneys
Dio2 is responsible for conversion of T4 to T3 in the thyroid, placenta and brain
Your sister's TA result is likely to account for her milder symptoms because her T4 to T3 conversion is less impaired, and therefore better than yours (AA), which means she very likely has a higher percentage level of T3 in her body.
T3 is the active thyroid hormone, which, for good health, is required by every cell in the body in a constant and adequate supply. To work, T3 needs to enter the nuclei of the cells.
I have the Dio2 variant, and a form of thyroid hormone resistance, consequently I need a supraphysiological dose of T3 to function.
Perhaps someone else will pop in with a more detailed explanation!
Hi DD, thanks for your reply. I’m learning more as I continue on my hypo journey. My sister doesn’t have such bad symptoms as I had at the start, just a touch of brain fog but she’s still going to see an endo - just in case! I’ve had great improvement since going onto T3 only and my endo has been increasing dose gradually. Like you, I may possibly be resistant as I’m up to 50mcg now and still feel as though I could use more.
If there is any doubt she needs to have a full thyroid test. ...not the basic NHS one!
If required a genetic test usually comes after those results have been evaluated but I'm not convinced that it is always necessary.
High FT4 with low FT3 suggests poor conversion and the first step is to optimise the nutrients below, test again and if no improvement then consider adding T3.
Full test- TSH, FT4, FT3, vit B12, vit D, folate ferritin and antibodies but I guess you've been there!
As you know being " in range" means nothing, it's important to find the point within that range that is optimal for the individual..... and where they feel well. Don't accept "in range" or "normal" as an interpretation of labs. FT4 and FT3 must be compared.
Doctors are pretty clueless about thyroid disease, they are taught very little in med school which is why so many patients arrive here.
There is a genetic test which detects faulty alpha and beta T3 receptors ( basic description!!) but there are other causes of resistance though not all understood.
I had no tests. I just read as much as I could... and experimented!
Once I moved to T3-only and kept slowly increasing the dose with no signs or symptoms of overmedication I eventually reached a dose that I knew I could only tolerate if I had a type of hormone resistance. My maximum dose was 212.5 mcg, I now take 81.25mcg.
Hello SlowDragon, my sister isn’t on any thyroid meds. Her GP told her test results ‘in range’ but she’s going to see an endo ( possibly mine) to make sure that is the case. Thanks for your reply
Strongly recommend she get FULL Thyroid and vitamin testing done before consultation with endocrinologist
She’s legally entitled to copies of all GP test results and ranges that have been done already
For full Thyroid evaluation she needs TSH, FT4 and FT3 plus both TPO and TG thyroid antibodies tested.
Very important to test vitamin D, folate, ferritin and B12
Is she currently taking any vitamin supplements ?
Low vitamin levels are extremely common, especially with autoimmune thyroid disease (Hashimoto’s or Ord’s thyroiditis)
Low vitamin levels common as we get older too
Recommended on here that all thyroid blood tests should ideally be done as early as possible in morning and before eating or drinking anything other than water (and last dose levothyroxine 24 hours before test )
This gives highest TSH, lowest FT4 and most consistent results. (Patient to patient tip)
Private tests are available as NHS currently rarely tests Ft3 or all relevant vitamins
If TPO or TG thyroid antibodies are high this is usually due to Hashimoto’s (commonly known in UK as autoimmune thyroid disease). Ord’s is autoimmune without goitre.
About 90% of all primary hypothyroidism in Uk is due to Hashimoto’s. Low vitamin levels are particularly common with Hashimoto’s. Gluten intolerance is often a hidden issue too
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