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!


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

  1. Janet said:

    Oct 28, 09 at 10:32 am

    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 said:

    Oct 28, 09 at 10:42 am

    Ya think??? LOL!

  3. DAwn said:

    Oct 28, 09 at 4:12 pm

    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.

    Dawnx

  4. Bill said:

    Oct 28, 09 at 4:45 pm

    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 said:

    Oct 28, 09 at 5:50 pm

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

  6. Helga Hansen said:

    Oct 29, 09 at 2:43 pm

    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 said:

    Nov 06, 09 at 4:48 pm

    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 said:

    Nov 16, 09 at 12:01 pm

    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


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