Proof of Concept: T3 > T4

In conventional medicine, hypothyroid patients are treated w/levothyroxine which is the synthetic sodium salt of natural thyronine.  Since the 1930s, L-T4 has been used because of several (potential) benefits: lack of antigenicity, chemical stability, uniform potency, and once daily dosing.  This compares to dessicated porcine thyroid which can be antigenic (think of porcine insulin which has largely been replaced by synthetic but essentially bio-identical insulin) and varies in potency (T3:T4 varies from batch to batch, although T7 remains about the same).

The use of L-T4 (levothyroxine) presumes that T4 is converted into T3 uniformly throughout the body.  Yet many patients complain of persistence of hypothyroid symptoms even when their TSH is fully corrected w/T4.  Recent animal studies have demonstrated that, in fact, peripheral conversion of T4 into T3 is not always consistent w/TSH which represents pituitary levels.

In a small and short but elegant study published this month in JCEM, the authors randomized 14 patients w/hypothyroidism to either L-T4 or L-T3.  To account for and blind both the researchers and patients to the short-half life of L-T3, all patients were given their thyroid medications in a three times a day regimen.  Bear in mind that in the real world, this regimen frequency would lead to very poor adherence and thus poor (dissimilar) results.  However, in this ideal setting, the authors demonstrated that L-T3 lead to weight loss & improvement in lipids without any side effects when compared to L-T4 dosed to achieve the same TSH over 6 weeks.  

Additionally, I should point out that the authors aimed for a TSH of 0.5-1.5mU/L which is at the low end of the typical normal reference range 0.4-4.5mU/L.  In the real world, most physicians declare their patients adequately replaced as soon as their TSH drops below 4.5mU/L such that the numerical result is no longer highlighted, boldfaced, and/or labeled abnormal.  But if you recall my grade school analogy, that's the same as tutoring a failing student to a D minus grade rather than the helping the student reach his/her potential.

Regardless, I think this small, short proof-of-concept raises several points to ponder.  First and easiest, consider replacing L-T4 to achieve a lower TSH than commonly accepted, assuming no side effects.  Just bear in mind that bone loss might become more problematic.  Second, if hypothyroid symptoms persist once TSH is pushed to the lower limit of normal, consider supplementing w/L-T3 (liothyronine) three times daily, assuming that the patient's medication adherence is better than most.

But remember that even the authors admitted that compliance will be the biggest issue with which to deal, at least until pharmaceutical manufacturers develop a slow or extended release version of L-T3.

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