Is there a genetic reason many of us do lousy on T4?

deiodinase2Last May, a very interesting article appeared in the May 2009 issue of the Journal of Clinical Endocrinology and Metabolism, titled For Some, L-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale and presented by Endocrinologists in Bristol in the UK. It’s accompanied with an editorial by Endocrinologists Brian W. Kim and Antonio C. Bianco.

This is the same article referred to by Endocrinologist Dr. Gary Pepper on the last Thyroid Patient Community Call on Talkshoe.

Basically, the article states that a genetic variation in the enzyme that converts T4 to T3, deiodinase D2 (also called Type 2 Deiodinase, or 5′-Deiodinase), may be responsible for why so many thyroid patients don’t do well on Synthroid, Levoxyl, levothyroxine, etc, and in turn, do so much better on natural desiccated thyroid like Naturethroid, Erfa’s Thyroid, or the combined synthetic T4 and synthetic T3 (Cytomel).

In other words, where some may have a strongly functioning deiodinase D2 enzyme which converts T4 to the active T3 well, others may have a modified deiodinase D2 enzyme, causing less optimal conversion.

In the Editorial, the two Endos Kim and Bianco explain the reality of “polymorphism”–a condition in nature in which changes or variations occur, and in one patient from another, a change in the DNA.  As related to conversion of T4 to T3,  some thyroid patients have a less effective deiodinase D2 enzyme in the conversion of T4 to T3.  Specifically, there is a common variant of the gene, threonine (Thr) 92 alanine (Ala), and it results in decreased D2 enzymatic activity.

The study proposes that this alteration from polymorphism occurs in 16% of those studied, and concludes that the majority don’t have this problem, and thus, “most do fine on T4-only medications”. But 16% do have this problem and need the combined therapy of T4 with T3.

Bristol was also mentioning this reality in 2004 here, even if they thought it was as low as 5%.

As Dr. Pepper hinted, this study could do wonders to open the eyes of Endocrinologists about the use of desiccated thyroid, or at the very least, about combined hypothyroid treatment with synthetic T3 added to synthetic T4.  And I’m glad for that when so many patients have found Endocrinologists to be narrow-mindedly stuck on Synthroid or other T4-only thyroxine products.

Of course, informed thyroid patients know this is only a baby step in the right direction, even if a good one! So we’ll rejoice for this study, and watch for more progress from the medical community and Endocrinology in general. For example, saying that “most do fine on T4” simply because they have may a non-variation might be proven wrong as physicians take the time to really look at those “fine” patients, especially as they age and symptoms of an inferior treatment do pop up. And though the combination of synthetic T3 with synthetic T4 definitely gives better results, thyroid patients who then moved to desiccated thyroid with it’s T4, T3, T2, T1 and calcitonin report even better results and clinical presentation!  We’ve also learned that the TSH lab test absolutely sucks when it comes to diagnosis and treatment.  Read TSH Why It’s Useless, or see even more detail in Chapter Four of the STTM book, titled Thyroid Stimulating Hooey.

And finally: do thyroid patients really believe that problems with T4-only treatment is simply due to a genetic abnormality or variation? Maybe. But isn’t it funny that a healthy human thyroid does NOT depend solely on conversion, but also gives direct T3. hmmmmmm

P.S.  Patients also know that the use of the supplement Selenium helps with conversion, by the way, but has never stopped our first-hand knowledge that desiccated thyroid rocks!

10 Responses to “Is there a genetic reason many of us do lousy on T4?”

  1. Janet

    SO true. It’s a small step. Let’s hope some endos get a clue and start opening their eyes and ears and LISTENING to us. …A small light at the end of a LOOOOONG tunnel. 😉

    Thanks, Janie!

  2. Amber

    Ya think??? LOL!

  3. DAwn

    Yes its a good thing it is out, however it has been documented about that enzyme for some time. The endos in my opinion if they look know all these things and just choose to ignore it because lets face it, it is easier for them to treat as they do than balance people with weak adrenals andx get them up to speed with T3 containing meds, only ‘simple hypos’ tend to be easy to balance from what I have seen. I don’t mean simple in a derogatory way, I just mean that the people who suffer simply from sluggish output are easiest to treat with no peripheral conversion or receptor problems and no yoyoing from thyroiditis.
    I also wish they would notice that hypothyroidism secondary to autuimmune thyroiditis cannot be simply pumped up with T4 also. They have a lot of research to do.


  4. Bill

    Dawn, I have Hashimoto’s (diagnosed 20 years ago). I’m a newbie to natural thyroid treatment and I’m curious about what you said. Could you explain what you mean by, “hypothy­roi­dism secon­dary to autuim­mune thy­roi­di­tis can­not be simply pum­ped up with T4”.

    Sorry if this is the wrong place to post a question like this. b

  5. Nan

    Am printing this and taking it to my endo appt next week.
    Thank you!

  6. Helga Hansen

    Bill, I think it’s because autoimmune thyroiditis is about the body attacking the thyroid via the anti-bodies, and it would be ideal to stop *that* from happening, rather than just taking T4, which might actually make matters worse.

    Basically, Hashimoto’s is an immune disorder, which creates a thyroid disorder, and patients who are taking synthetic T4 are having to continually increase their dosage, because the thyroid is still being destroyed by the body.

    So what Dawn is saying is that hypothyroidism secondary to (caused by) autoimmune thyroiditis will not respond to T4 alone, and any decent (haha) endocrinologist worth his/her salt would know this!!

  7. Kathy

    I was diagnosed Hashi/hypothyroid almost four years ago and have seen four different doctors who’ve kept me on natural thyroid replacement. The last Endo berated me for using Armour,“an unstable and inferior drug”, but grudgingly prescribed it. I was recently seen by an M.D. that is in a Naturopathic Practice. Despite treating many of her patients with Armour she suggested I might respond better to a Synthroid/Cytomel combo. She took time to explain that her training was that Hashimoto’s can attack natural thyroid replacement as it did my own thyroid. Because my TSH was up to 9 and both T3 and T4 were low she kept me on natural thyroid (increased dose and wrote script for compounded, due to Armour unavailability) and is trying to treat other issues she found through additional tests she ordered. I’m severely iodine and vitamin D deficient and have almost no adrenal function. We decided to discuss a change to synthetics at a future visit. I’ve been unsuccessful with my search for an answer to this belief that Hashi’s can attack natural replacement. I’d appreciate if anyone can help!

  8. Bill

    Now it makes sense Helga. Thanks for that :0)

    Kathy, good for you for researching this. I suggest telling your naturopathic MD that you’re researching the subject on your own. Ask her for the text or research source re. her belief that that “Hashimoto’s can attack natu­ral thy­roid repla­ce­ment as it did my own thy­roid”.

    It’s an interesting idea to me because it makes a lot of sense. I’ve been on the synthetic t4 for 20 years because of Hashimoto’s and am new to the natural medication, Armour, for the past month. I still feel like s—.

    Any information you can pass along would be greatly appreciated. I’m also interested in how it was determined that you have almost no adrenal function.

    Janie has my permission if she wants to relay my email address to you re. this subject. (I don’t know if I should leave it here) b

  9. Gina

    I have been shifted between .137 and .150 for 5 years now because I my thyroid production eventually gets to high on .150 and I have hyper-thyroid symptoms and when I shift to .137 it’s ok for a while (typically 9 months) and then get hypo-thyroid symptoms. For a month my doc gave me .137 plus 5 mcg cytomel and nearly immediately I felt jittery in the morning shortly after taking the meds, queasy by lunch time, and foggy brained and exhausted by 6 p.m. I was very uncomfortable, felt sort of anxious/depressed and when I was tested 4 weeks later it showed my levels were too high. Now Im alternating .137 and .150 over the course of a week but still think that cytomel has promise for me. Should my doc have dropped the Synthroid even lower (say to .125 or .100 with the cytomel?


    (From Janie: your reactions to T3 mean you probably now have adrenal fatigue from being on the most inadequate treatment ever invented for hypothyroid. Read then join patient groups for more feedback: )

  10. Sallie

    I’m also printing this for my doc and endo who doesnt believe about conversion issues. He actually said ‘you were ok on T4 for years so why would you have a problem now’.


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