•The current guideline-based management of hypothyroidism recommends monotherapy with levothyroxine (LT4), titrated to maintain the level of thyrotropin within a euthyroid reference range. This has been successful for most people with hypothyroidism, but a substantial minority still report symptoms of hypothyroidism unexplained by a comorbid medical condition. LT4 is essentially a prodrug for triiodothyronine (T3), the thyroid hormone that acts on target tissues in the brain and the periphery. Thyroid hormone replacement with LT4 alone does not restore physiological tissue levels of thyroid hormones, particularly T3. During the last two decades, much interest has focussed on the potential of combinations of LT4 and T3 to provide a superior outcome to LT4 monotherapy for people with hypothyroidism, especially those with residual symptoms despite thyrotropin-optimized LT4. This review seeks to provide an overview of currently available evidence on combination (LT4 + T3) therapy to be used for personalized medicine in patients with hypothyroidism. A number of randomized, controlled trials (RCTs) have failed to demonstrate superiority for the combination therapy approach, largely due to non-physiological T3 doses. However, patients with hypothyroidism are highly heterogeneous in terms of their residual thyroid function, individual set points for optimal thyroid homeostasis and for the presence or absence of polymorphisms in deiodinase enzymes in tissues that activate and deactivate circulating thyroid hormones. Accordingly, these RCTs may have failed to demonstrate benefits of combination therapy in individual hypothyroid phenotypes. The pharmacokinetics of LT4 and T3 also differ, which is a barrier to their co-administration. Future clinical trials using LT4 + T3 tablets better suited for combination therapy will resolve the outstanding research questions relating to the place of LT4 + T3 combination therapy in the management of hypothyroidism.
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I like the way they say "Future clinical trials using LT4 + T3 tablets better suited for combination therapy will resolve the outstanding research questions relating to the place of LT4 + T3 combination therapy in the management of hypothyroidism". Sounds simple doesn't it? But it won't be unless they ditch the long held biases in the endocrinological community. At least they seem to recognise that previous trials have failed through the use of non-physiological doses of T3. But will they recognise that the T3 dose can vary hugely from one individual to the next and, in some cases, patients can't tolerate T4 at all and have to take T3 only.
“However, patients with hypothyroidism are highly heterogeneous in terms of their residual thyroid function, individual set points for optimal thyroid homeostasis and for the presence or absence of polymorphisms in deiodinase enzymes in tissues that activate and deactivate circulating thyroid hormones.”
Hurrah for this. Even if it is stating what is obvious to us all here.
"Importantly, the guideline recommends avoidance of LT4 +T3 combination therapy for pregnant women, as we have insufficient data on the safety of this approach for the growing foetus." Clearly the use of combination therapy for over a century is insufficient to convince them. Putting the boot on the other foot the evidence shows levothyroxine monotherapy is less safe and there has been no attempt to establish the safety of monotherapy.
Is there any research about how to lose weight when still only taking Levo. I have been on this for over 20 years and the weight is still increasing. Unless I reduce my intake to unsafe levels (I am a nurse so understand the relevant nutrition to maintain life) I do not lose weight. My BMI is 31. I have had one knee replacement and am waiting for another and also have Level 1 osteoporosis. Have been very active in past but not now due to knee pain. I am desperate.
Muchas Gracias! It’s very encouraging to hear the emerging advocacy for “future clinical trials using LT4 + T3 tablets better suited for combination therapy”. I hope they will contribute to “resolve the outstanding research questions relating to the [practical use] place of LT4 + T3 combination therapy in improving the [effective] management [and treatment] of hypothyroidism”. The first shards of light appearing in the Thyroid darkness! Gratis! Our long walk to freedom!
I have mixed feelings on reading this. Levo alone made me worse and gain a lot if weight. I was apprensive about using thiroyd from thailand but decided it couldnt ne any worse than levo. It was great and i managed to lose a lot if the weight i put on. 4 years down the line and now cant get thiroyd. After a bit if aggro with my doc and endo they agreed to give me t4/t3 combo and it has been good although i take slightly more than they tell me. If its in the form of one pill i dont know how i can adjust it. Dont really want to cope with another change
This is a little shot in the dark which may help. You are taking a fixed amount of T3 in a day. You could increase the effectiveness of the T3 by dosing more than once per period (day) which doesn't exactly fit into 24 hours.. I don't mean doubling up the dose but take the dose in the stagerred way in less than 24 hours between doses if that's how you do things. If taking several times a day just lengthen the times between doses so that you don't have exactly n doses/day but stagger them so that, overall you take less T3/day on each day. It's like playing catchup. You either take less per day or more, but you stagger the doses to level out what dose levels are best over the period. I need a graph to explain better.
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T4 & T3 combination therapy... day 9... awesome! 
Why the Hesitancy in Recommending Combination T3/T4 Therapy?
Studies on TSH for those on combined T3 T4 therapy 
