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Do we need still more trials on T4 and T3 combination therapy in hypothyroidism





Eur J Endocrinol. 2009 Oct 6. [Epub ahead of print]


Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?


Wiersinga W. W Wiersinga, Endocrinology & Metabolism, AMC, Amsterdam, 1105 AZ, Netherlands.



Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with T4 explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T4/T3 combination therapy over T4 monotherapy. However, each of these trials can be criticized, and none is perfect: most of them failed to mimick the physiological ratio of serum FT4 to FT3 concentrations. Development of a sustained-release T3 preparation given as a single night-time dose (together with levothyroxine once daily) might maintain physiological serum FT4 to FT3 ratio's throughout 24 hours. Genetic polymorphisms in deiodinase 2 and thyroid hormone transporters have been associated with well-being, fatigue, depression and greater improvement on combination therapy. Future trials should aim at carriers of these polymorphisms to see if they do better on T4/T3 combination therapy than on T4 monotherapy.


PMID: 19808902 [PubMed - as supplied by publisher]









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  • It is great to see recognition that some hypothyroid patients just do not get well on levothyroxine (T4) alone and that T3 (the most active hormone) may be required in these individuals. This reviewer is talking common sense by recognising the need to use slow-release T3 (available from compounding pharmacies) to maintain constant levels as would be produced in a healthy body. However, while noting genetic predisposition to reduced conversion of T4 to T3 the author fails to acknowledge that other factors can also affect this conversion e.g. nutritional deficiencies (selenium particularly), chronic stress/adrenal fatigue and heavy metal toxicity.

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