This is an update on the reasons why I could not get well using T4, T4/T3 or NDT medication. I need T3-Only medication in order to recover my health.
Firstly, I have a defective DIO1 and DIO2 gene.
I recently did the DIO2 gene test with Regenerus labs.
I have discovered that I have the homozygous variant of the DIO2 gene defect. I also inherited it from both of my parents. The fact that I inherited both copies (from both of my parents), makes the effect likely to have an effect. I am more likely to have poor conversion of T4 to T3.
The D2 deiodinase enzyme is used by the brain, pituitary, thyroid gland, heart, and muscles. D2 is far more efficient in converting T4 to T3 than D1.
See the Watts Study for more information on the DIO2 deiodinase gene defect:
I have also completed a 23andMe genetic test. I have the homozygous variant of the DIO1 gene mutation also (having both defects for both SNPs). Again, I inherited this from both parents. D1 is used by the liver and kidneys. D1 is less efficient in converting T4 to T3. However, in the liver D1 is very important, as it is used to clear rT3, i.e. to deiodinate it to T2, T1 and then T0 before removing it from the body within 24 hours. So, a DIO1 defect can cause higher rT3, because the rT3 will not be clearly so fast. We know that high rT3 also tends to lower the number of D2 deiodinase enzymes, thus making conversion of T4 to T3 even worse.
The DIO1 and DIO2 genes currently have three known SNPs or single nucleotide polymorphisms. These are ‘hotspots’ of known genetic variation, and I have copies of the mutations from both parents in every single case. See:
So, I have all the mutations for the relevant SNPs of DIO1 and DIO2, and in both cases, I have two copies. I was always likely to have conversion problems.
Secondly, Hashimoto’s destroyed my thyroid gland. This is another reason that so many with Hashimoto’s, or thyroidectomy patients, need additional T3.
The thyroid is the biggest converter of T4 to T3 in the body. The contribution of the thyroid gland to conversion is far more important than the liver, kidneys and peripheral tissues. The blood flowing through the thyroid gland carries FT4, and the thyroid converts some of this FT4 to FT3. The conversion contribution of the thyroid gland is more significant than any T3 produced by the thyroid itself in normal circumstances. The thyroid is responsible for 25% of our total circulating T3 (through T3 production and mostly through T4 to T3 conversion capability). So, when you lose thyroid tissue, you also lose this T3 and the important T4 to T3 conversion capability. It is gone – permanently!
Thirdly, I was also driven to T3 medication use, because I had extremely low cortisol levels when on T4 based medication.
The pituitary uses the D2 deiodinase enzyme to convert 80% of the T4 that passes through its cells. It keeps this converted T3 within its own tissues, i.e. the pituitary gland NEEDS high levels of FT3 in order to function. With worsening conversion through the DIO2 gene defect and the loss of thyroid conversion, On T4-based medication, I would have had lower T3 levels in the pituitary. This can induce dysfunction in the pituitary, and lower the output of ACTH and TSH. T3-Only is known to stimulate the hypothalamic-pituitary system and the mitochondria far more than T4 or T4/T3.
My cortisol levels were so poor, that my blood pressure was horribly low and I used to pass out quite often due to it. Only when I managed to rectify my hypocortisolism (low cortisol) through the use of T3 and the Circadian T3 Method (CT3M), did I begin to recover.
Note: Anything that lowers T3 levels, including lower conversion through any mechanism, e.g. DIO1 or DIO2 gene mutations, or any other mechanism or nutrient defect, can affect the pituitary, and the way it is supposed to work. It is not surprising that so many thyroid patients also have low cortisol issues.
The three things above combined to be a perfect storm for me. One that made using T4 impossible.
I believe the above points may be relevant to a vast number of thyroid patients.
I was driven to need T3 in order to compensate for the active effects of the DIO1 and DIO2 gene defects, plus the loss of conversion capability due to Hashimoto’s. On top of all of this, when someone takes T3 it tends to suppress TSH more effectively than T4 medication. A low TSH reduces T4 to T3 conversion, see my books and:
The combination of everything above would have made it very difficult for me to recover with a T4 or T4/T3 combination.
I cannot cope with T4 medication, even in small amounts. T4 in any quantity brings back my hypothyroid symptoms.
I am healthy, fit, active and symptom-free whilst on T3 replacement therapy. So, when I hear views like, “Everyone needs some T4”, I would like to be able to respond, “Why would I wish to be ill once again, just to appease your incorrect view!” These types of views are stated from time to time, usually by doctors, but also, sometimes by thyroid patients. Unsurprisingly, the patients concerned that make these statements are usually on some form of T4, T4/T3 or NDT medication. They think everyone else should be taking it too. They have sometimes found a not especially compelling piece of research that shows that T4 has some minor effect on some systems in the body, and they extrapolate from there that everyone needs T4. This is not the case. One of the big flaws in that type of argument is that people who are living well on T3 alone have not been studied for the compensatory adjustments that the body makes when using T3 on its own. The other big flaw is that small pieces of research are often found to be inadequate or incomplete when further research comes along, e.g:
I have used T3 replacement for over twenty years. I know many thyroid patients, who have recovered their health using T3-Only and have been using it for a very long time. There well-understood reasons that explain why I could not get well on more conventional T4-based (T4/T3 or NDT) thyroid treatment.
T3 replacement therapy can be a very effective, safe, long-term thyroid hormone treatment. There are far too many thyroid patients like me who are well on T3-Only to doubt its value as a useful thyroid treatment for those who cannot get well with any T4 based therapy (NDT and T4/T3 included).
Research will prove me right. The current prevailing attitude of negativity to T3 therapy will eventually be blown away when the research that is already known is accepted and more research occurs.
(Updated in November 2019)